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Incidence and risk factors for poor ankle functional recovery, and the development and progression of posttraumatic ankle osteoarthritis after significant ankle ligament injury: The Significant Ankle Ligament Injury (SALI) Cohort study

Summary:
Osteoarthritis (OA) is the most common joint disorder, and is a common cause of disability in adults in the Western World. Joint injury has been linked to the development of OA and while a lot of research has focused on injury and OA in the knee and hip, very little work has looked at the ankle, where around 80% of ankle OA is due to injury. Ankle sprains are common, accounting for up to 5% of all Emergency Department (ED) visits in the UK every year. They are often thought of, and treated as, minor injuries, and yet as many as half of people who suffer a severe ankle injury do not fully recover and end up with some lasting ankle problems that can limit the persons lifestyle. The purpose of this study is to provide new knowledge about:

1) The type of people who attend ED suffering a significant ankle ligament injury
2) What it is about those people and their injury that may mean they go on to develop OA
3) What things influence this chance i.e. who is more likely and who is less likely to go on to develop OA after a significant ankle ligament injury

Participants will complete questionnaires at 7 time-points; at time of presentation to ED, and then at 3 months, 12 months, 3 years, 5 years, 10 years and 15 years post injury. In addition matched controls will be recruitment, completing the same questionnaires at each of the 7 time-points

Inclusion criteria:
Patients between 18 and 70 years of age, with isolated ankle injuries, who meet the Ottawa Ankle Rules positive
(OAR+) criteria (Buffalo modification), but are negative for a significant ankle fracture on subsequent x-ray,
will be included in the study.

Exclusion criteria:
Any patient under the age of 18 yrs or over 70yrs; all x-ray reported significant ankle fractures (excepting flake fractures); fracture injuries of the hindfoot, midfoot or forefoot will all be excluded from the study. Patients with any other significant concurrent joint injuries, including contralateral ankle injury and upper limb injuries, will also be excluded. Patients who are not independently living; or those who are unable to read English, will be excluded from the study.

Principal Investigator for this trial: Miss Brigitte Scammell

Research Ethics Committee Reference: 15/EM/0384

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Incidence and risk factors for poor ankle functional recovery, and the development and progression of posttraumatic ankle osteoarthritis after significant ankle ligament injury: The Significant Ankle Ligament Injury (SALI) Cohort study

Summary:
Osteoarthritis (OA) is the most common joint disorder, and is a common cause of disability in adults in the Western World. Joint injury has been linked to the development of OA and while a lot of research has focused on injury and OA in the knee and hip, very little work has looked at the ankle, where around 80% of ankle OA is due to injury. Ankle sprains are common, accounting for up to 5% of all Emergency Department (ED) visits in the UK every year. They are often thought of, and treated as, minor injuries, and yet as many as half of people who suffer a severe ankle injury do not fully recover and end up with some lasting ankle problems that can limit the persons lifestyle. The purpose of this study is to provide new knowledge about:

1) The type of people who attend ED suffering a significant ankle ligament injury
2) What it is about those people and their injury that may mean they go on to develop OA
3) What things influence this chance i.e. who is more likely and who is less likely to go on to develop OA after a significant ankle ligament injury

Participants will complete questionnaires at 7 time-points; at time of presentation to ED, and then at 3 months, 12 months, 3 years, 5 years, 10 years and 15 years post injury. In addition matched controls will be recruitment, completing the same questionnaires at each of the 7 time-points

Inclusion criteria:
Patients between 18 and 70 years of age, with isolated ankle injuries, who meet the Ottawa Ankle Rules positive
(OAR+) criteria (Buffalo modification), but are negative for a significant ankle fracture on subsequent x-ray,
will be included in the study.

Exclusion criteria:
Any patient under the age of 18 yrs or over 70yrs; all x-ray reported significant ankle fractures (excepting flake fractures); fracture injuries of the hindfoot, midfoot or forefoot will all be excluded from the study. Patients with any other significant concurrent joint injuries, including contralateral ankle injury and upper limb injuries, will also be excluded. Patients who are not independently living; or those who are unable to read English, will be excluded from the study.

Principal Investigator for this trial: Miss Bridgitte Scammell

Research Ethics Committee Reference: 15/EM/0384

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Correlates of sedentary behaviour and physical activity in Rheumatoid Arthritis (RA) and Osteoarthritis (OA)

Summary:
Moderate-to-vigorous physical activity (MVPA) is recommended for people with Rheumatoid Arthritis (RA) and lower
limb Osteoarthritis (OA) in order to improve physical and psychological health, as well as to reduce the joint pain,
disease-related inflammation, and associated physical dysfunction symptomatic of these conditions. However, the
physical dysfunction resulting from RA and OA also means that most individuals living with these conditions do not
engage in sufficient levels of MVPA to experience these health benefits.
Reducing sedentary behaviour (e.g., time spent sitting, lying) may be perceived as more manageable than increasing
MVPA for people with RA and OA. Recent studies in older adults have suggested that reducing sedentary behaviour
might help to improve physical function, enhance psychological health, and lessen systemic inflammation. Importantly,
the positive health benefits of reducing sedentary behaviour are reported to occur regardless of levels of MVPA
participation.
Currently, we know little about the physical and psychological health implications of sedentary behaviour for RA and
OA, as well as factors predictive of both sedentary time and MVPA engagement. In addition, we do not know if the
possible health implications of sedentary behaviour are independent from the health benefits of MVPA engagement for
these individuals.
The primary aim of this research is therefore to investigate (and compare) the determinants and health consequences
of objectively measured MVPA and sedentary behaviour in RA and OA. The research will be conducted at Russells Hall
Hospital (Dudley). Patients who consent will be asked to participate in 2 ‘study weeks’, 6 months apart. At the start and
end of each study week, participants will be asked to complete questionnaires, provide a fasted blood sample (RA
only), and undertake assessments of height, weight, body composition, and blood pressure. Participants will also be
given an accelerometer to wear for 7 days during the study week.

Inclusion criteria:
Rheumatoid Arthritis:
1. Patients must be clinically diagnosed with RA (ACR Clinical Classification Criteria; Aletaha et al., 2010).
2. Aged 18 years old and above.
Osteoarthritis:
1. Adults above 45 years of age.
2. Physician-made diagnosis of hip or knee OA regardless of radiographic evidence (confirmed by the consultant or
research nurse who will introduce the study to the participant).

Exclusion criteria:
Rheumatoid Arthritis:
1. Patients unable to ambulate independently, or with the use of a walking aid (e.g., walking stick)
2. Individuals will also be excluded if they have been diagnosed with fibromyalgia, gout, or lupus
3. Presence of any mental illness that causes significant memory loss, for example, Alzheimer’s disease and
vascular dementia
Osteoarthritis:
1. Patients unable to ambulate independently, or with the use of a support or aid (e.g., walking stick).
2. Co-existence of other forms of arthritis such as rheumatoid arthritis, fibromyalgia, gout, lupus (self-reported).
3. Individuals will also be excluded if they have been diagnosed with any mental illness that causes significant
memory loss (e.g., Alzheimer’s disease and vascular dementia [self-reported]).
Other exclusion criteria relevant to main protocol sub-section (RA only):
1. Cortisol awakening response – Patients taking corticosteroid treatment will be excluded from the section of the study
protocol that concerns assessment of the cortisol awakening response (i.e., saliva samples – corticosteroids will
interfere with hormone secretion/regulation and confound measurement of cortisol in saliva)

Principal Investigator for this trial: Dr A Abhishek

Research Ethics Committee Reference: 16/WM/0371

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

The SCOTTY Study – whole genome sequencing study of young colon cancer patients and their parents.

Summary:
Cancer of the large bowel (colorectal cancer) is common in the general population and the lifetime risk for someone living in the UK is 1 in 17. Whilst modern surgery, radiotherapy and chemotherapy treatments have impacted beneficially on survival outcome, many patients still die from their disease. Hence, there is a pressing need to understand the causes of colorectal cancer and to intervene early. Colorectal cancer under the age of 40 years of age is particularly rare, with less than 1.2% of all cases aged Inclusion criteria:
PATIENT INCLUSION CRITERIA

•Patients who have developed colorectal cancer at aged 40 years of age or younger at the time of diagnosis.
(Individuals OVER the age of 40 years ARE eligible if they were previously diagnosed with colorectal cancer when aged 40 years or younger).

•Patients will not have a known molecular genetic predisposition to the development of colorectal cancer or a strong family history of cancer consistent with known dominant disorders.

•Patients are able to provide written informed consent for whole genome sequencing and blood/saliva biomarkers.

•Documentary evidence of a pathologically confirmed adenocarcinoma of colon or rectum along with consent to access archived tumour material from the time of operation.

•Demographic and drug history are available or can be ascertained from patient.

•If the patient is under the age of 16 years, both parents are available to sign/countersign a consent form. Whilst
cases under the age of 16 years are extremely rare, these cases greatly enhance the value of their contribution to the study.

•Inclusion can be from any part of mainland GB and Northern Ireland and of any ancestry.

•Patients will be asked if they agree to being re-contacted if further confirmatory samples are required and/or results are of clinically significant relevance.

PARENTS INLCUSION CRITERIA

•Neither parent will have had a past or present diagnosis of colorectal cancer or other cancer relevant to CRC
predisposition such as endometrial cancer.

•Both parents will be alive and are contactable within the United Kingdom and Northern Ireland.

•Both parents will not have a known genetic predisposition to the development of colon cancer.

•Both parents will be able to provide written informed consent for sampling.

•Both parents will provide a simple blood sample for whole genome sequencing & blood or saliva biomarkers.

•Demographic and drug history are available or can be ascertained from parents.

•Both parents will be asked to agree to being re-contacted if further confirmatory samples are required and/or results have clinical implications.

Exclusion criteria:
– BOTH parents unable to provide samples.
– The inability to provide informed consent.
– Patients who have developed CRC aged over 40 years at diagnosis.
– Tumour that has shown loss of DNA mismatch repair gene protein expression or tumour that has exhibited MSI (micro satellite instability).
– Familial CRC (a strong family history)

Exclusion criteria – PARENTS

– Both parents are unable to provide samples.
– The inability to provide informed consent.

– Known mutations in colorectal susceptibility genes within the family (eg APC,MLH1, MSH2, MSH6, PMS2, MUTYH, POLE1, POLD1, SMAD4/BRCA/STK11).

Principal Investigator for this trial: Dr Abhijit Dixit

Research Ethics Committee Reference: 16/SS/0082

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Study to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease

Summary:
Crohn’s disease is a long-term condition that causes inflammation of the lining of the digestive system. Inflammation can affect any part of the digestive system, but most commonly occurs in the last section of the small intestine or the large intestine.
The purpose of part I of the study is to see if JNJ 6430450, the study drug is useful for treating patients with moderately to severely active Crohn’s Disease. The study is also done to see if JNJ-64304500, is safe to take without causing too many side effects. In addition to this the purpose of Part II is to find the dose of JNJ 64304500 that best treats moderately to severely active Crohn’s Disease and to understand patient responses to Crohn’s diseases treatments
using an approved drug called ustekinumab.
This is double-blinded study meaning that neither the participant and the study doctor will know which medication is
being given. The study is randomised, meaning that participants will be randomly assigned to receive either JNJ-
64304500, or placebo in part 1 or JNJ-64304500, placebo or ustekinumab in part II.
Janssen Research & Development, LLC is the sponsor of this study which will take place worldwide. It is anticipated that approximately 200 participants will be enrolled in Part I and an additional 250 participants will be enrolled in Part II.

Inclusion criteria:
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Be a man or woman >18 years of age.
2. Have Crohn’s disease or fistulising Crohn’s disease of at least 3 months’ duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
3. Have active Crohn’s disease, defined as a baseline CDAI score of >220 but 0.3 mg/dL [>3.0 mg/L])
OR
b. Calprotectin >250 mg/kg.
5. In Part I, meet the following requirements for prior or current medications for Crohn’s disease:
a. Has previously demonstrated inadequate response, loss of response, or intolerance to 1 or more approved biologic
therapies (eg, infliximab, adalimumab, certolizumab pegol, or vedolizumab) as outlined in Attachment 1 of the protocol.
OR
b. Has failed conventional therapy:
1) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, 6-MP, or
MTX) at adequate therapeutic doses.
OR
2) Has a history of failure to respond to or tolerate an adequate course of
corticosteroids and/or immunomodulators (ie, AZA, 6-MP, or MTX)
OR
3) Is corticosteroid dependent or has had a history of corticosteroid dependency.
6. In Part II, meet the following requirement for prior or current medications for Crohn’s disease: has previously
demonstrated inadequate response, loss of response, or intolerance to 1 or more approved biologic therapies (eg,
infliximab, adalimumab, certolizumab pegol, or vedolizumab) as outlined in Attachment 1 of the protocol.
7. Adhere to the following requirements for concomitant medication for the treatment of Crohn’s disease, which are
permitted provided that doses meeting these requirements are stable, or have been discontinued, for at least 3 weeks
before baseline (Week 0), unless otherwise specified:
a. Oral 5-aminosalicylic acid (5-ASA) compounds.
b. Oral corticosteroids at a prednisone-equivalent dose at or below 40 mg/day, or 9 mg/day of budesonide, or 5 mg/day
beclomethasone dipropionate.
c. Antibiotics being used as a primary treatment of Crohn’s disease.
d. Conventional immunomodulators (ie, AZA, 6-MP, or MTX):participants must have been
taking them for at least 12 weeks and at a stable dose for at least 4 weeks before
baseline.
8. A participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50
years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during
screening). Adenomatous polyps must be removed before the first administration of study agent.
9. A participant who has had extensive colitis for ≥8 years, or disease limited to the left side of the colon for ≥12 years,
must either have had a colonoscopy to assess for the presence of dysplasia within 1 year before the first
administration of study agent or a colonoscopy to assess for the presence of malignancy at the screening visit, with no
evidence of malignancy
10. Have screening laboratory test results within the following parameters:
a. Haemoglobin ≥8.0 g/dL.
b. White blood cell count (WBCs) ≥3.0 × 103/μL.
c. Neutrophils ≥1.5 × 103/μL.
d. Platelets ≥100 × 103/μL.
e. Serum creatinine Exclusion criteria:
Any potential participants who meets any of the following criteria will be excluded from participating
in the study:
1. Has complications of Crohn’s disease such as symptomatic strictures or stenoses, short gut syndrome, or any
other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess
response to therapy, or would possibly confound the ability to assess the effect of treatment with JNJ-64304500 or
ustekinumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary
if drained and adequately treated at least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal
abscesses, provided that there is no anticipated need for any further surgery. Participants with active fistulas may be
included if there is no anticipation of a need for surgery and there are currently no abscesses identified.
3. Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before
baseline.
4. Has a draining (ie, functioning) stoma or ostomy.
5. Has received any of the following prescribed medications or therapies within the specified period:
a. IV corticosteroids Principal Investigator for this trial: Dr Gordon Moran

Research Ethics Committee Reference: 16/EE/0356

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Defining the evidence base for health care delivery in congenital adrenal hyperplasia – a multi-centre CAH-UK (Children & Adolescents with CAH in the UK) initiative)

Summary:
Congenital Adrenal Hyperplasia (CAH) is associated with significant morbidity and mortality and occurs in about 1 in 10,000 life-births (about 6,300 individuals in the UK). Recent clinical data suggest impaired heath in young adults with CAH. The onset of such problems during childhood remains unclear. However, it is of paramount importance to define an evidence base to develop strategies for secondary prevention of future health problems. To define novel predictive markers of long-term health problems, we have formed a clinical consortium (CAH-UK) involving 16 tertiary UK centres to explore the current health status in 8 to 18 year olds with CAH. We have designed a cross-sectional study to define the current health in children and young people with CAH in the UK. These patients undergo there to six monthly blood tests as part of the routine clinical care. We have planned to add on additional blood, urine and saliva collections to devise novel test and explore the metabolic status. In addition, we will for the first time define if quality of life is already altered at this young age as it is in young adults. We will establish the presence and onset of potential health problems in children and young persons with CAH in the UK. Study participants will have an immediate benefit from this study as their therapy can be individualised. After validation novel markers of disease control will be implemented into clinical practice within the next 2-3 years improving personalisation of treatment in all patients with CAH. The identification of altered health related quality of life would aid developing care strategies. This combination of investigations represents a major step towards a personalised therapeutic approach in CAH.

Inclusion criteria:
Patients with CAH
1) Patients with known CAH due to 21-hydroxylase deficiency confirmed by hormonal and/ or genetic testing
2) Aged 8 – 18 years
3) Participants must have capacity to assent/consent and provide a signed and dated informed consent.

Controls
a) Aged 8 – 18 years
b) Participants must have capacity to assent/consent and provide a signed and dated informed consent.

Exclusion criteria:
Patients with CAH
1) Pregnancy

Controls
1) Past or present history of an endocrinopathy (all stages)
2) Type 1, diabetes, Type 2 diabetes, Insulin resistance
3) Known conditions of lipid/ cholesterol metabolism
4) Presence of any psychiatric disorder
5) Current or past use of psychiatric medication
6) Glucocorticoid use within the last 6 months
7) Diagnosed learning difficulties and/or full-scale IQ Principal Investigator for this trial: Dr Tabitha Randell

Research Ethics Committee Reference: 15/YH/0537

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

GRAD – Can genomics predict dysphagia after head and neck radiotherapy?

Summary:
This study will assess the feasibility of biomarker studies that can identify head and neck (HN) cancer patients at high
risk of developing severe complications following radiotherapy or chemoradiotherapy. Some patients develop severe
complications including difficulty with swallowing, limited mouth opening and ORN – osteoradionecrosis (irreversible
damage to bone) while others who have had the same treatment do not. Radiation damage can reduce quality of life
and or cause early death. Although previous research suggests that genetic variations may be associated with postradiation
tissue damage (radiotoxicity), we currently have no means of predicting how individual patients will react to
radiation. If we could identify patients with high radiotoxicity risk, their treatments could be modified by using surgery as
the primary treatment, by using novel targeted therapies that are directed at cancer cells only or by reducing the
radiation dosage to tissues involved in swallowing.
Genome wide association studies (GWAS) search for small genetic variations, called single nucleotide
polymorphisms (SNPs) that occur more frequently in people with a particular characteristic than in people without. We
will use GWAS look at thousands of SNPs at the same time.
HN cancer patients who have completed their primary radiotherapy or chemoradiotherapy treatment within the last 1 to
5 years will be eligible to participate. Patients who have had HN surgery are ineligible. Consenting patients will be
asked to complete a short swallowing function questionnaire and record whether they have limited mouth opening,
tube feeding or have suffered from ORN post treatment. The 100 patients with the most severe swallowing problems
and 100 with minimal problems will be asked to attend a research clinic to provide saliva and blood samples for
GWAS. If new genetic associations are identified, researchers can use this information to inform further gene specific
radiotoxicity studies in the future.

Inclusion criteria:
Patients who have been treated for first head and neck cancer with radiotherapy or chemoradiotherapy
Patients who are between 1 and 5 years post treatment

Exclusion criteria:
Those patients not deemed able to give informed consent
Patients who have had laryngeal cancer
Patients who have had thyroid cancer
Patients who have had head and neck surgery

Principal Investigator for this trial: Dr Judith Christian

Research Ethics Committee Reference: 14/LO/0429

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A PHASE Ib, BLINDED, RANDOMIZED,MULTICENTER, MULTIPLE-ASCENDING DOSESTUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF UTTR1147A ADMINISTERED BY SUBCUTANEOUS INJECTION IN PATIENTS WITHNON-HEALING NEUROPATHIC DIABETIC FOOTULCERS

Summary:
Ulceration of the foot associated with diabetes mellitus is a common and disabling condition. Besides control of the
underlying diabetes, the current best standard of care (SOC) for Diabetic Foot Ulcers (DFUs) includes local ulcer care
with frequent cleaning and debridement, (removal of dead and hard skin, usually with a scalpel) control of any
infection, pressure-relieving strategies, and restoration of blood flow to the foot if needed.
The aim of this study is to test the safety of study drug UTTR1147A at different dose levels. UTTR1147A is a version of
a protein called interleukin-22 which helps to fight infection and repair tissue damage by encouraging the growth of
new tissue. There is currently only one ongoing study of UTTR1147A in healthy volunteers. Because the results are
blinded, not all of the side effects of this treatment are known.
This study is sponsored by Genentech Inc. About 66 – 90 patients, will take part in this double blind placebo
controlled study at approximately 15 sites in Europe. There will be at least 18 study visits if the patient’s ulcer remains
open through the duration of treatment. If the patient’s ulcer is still open at the end of the treatment period, the patient
will be followed weekly and SOC ulcer treatment will continue for 8 weeks in the observation period. If an ulcer is
confirmed closed at any time during the study, the patient may be followed every 4 weeks during the observation
period. Procedures involved include a physical examination, vital signs (pulse and blood pressure), blood tests,
ECGs, a foot X-Ray, tests for blood flow to the affected foot and DFU related assessments.
Based on the patient’s status of their DFU at the end of the 2-week run-in period (infected or not), patients will be
randomly assigned to one of 4 treatment cohorts (A. B, C or D) to receive either UTTR1147A or placebo. Cohorts A, B,
or D, will have a 2 to 1 chance of being treated with UTTR1147A. Group C have an equal chance of receiving either
UTTR1147A or placebo. Patients in Cohort D will undergo small biopsies from the edge of the ulcer in addition.
Neither the participant nor the study doctor will know what treatment was assigned.

Inclusion criteria:
• Signed Informed Consent Form
• Age ≥ 18 to ≤ 80 years
• Up to date on all age-appropriate cancer screenings per local standards or, if
not up to date or not sure about their status, document their understanding of the possible tumor-promoting risks of
UTTR1147A
• Have a diagnosis of Type 1 or Type 2 diabetes. Diagnosis may be established by medical records and history of
treatment or HbA1c ≥ 6.5%.
• Peripheral neuropathy that is confirmed by demonstrating loss of sensation with
use of a 10 g (5.07 Semmes-Weinstein) monofilament (IWGDF 2015)
• Have adequate circulation to the foot as documented by an Ankle Brachial
Index (ABI) > 0.7 AND at least one of the following:
Toe Brachial Index (TBI) ≥ 0.50
Doppler waveform in the posterior tibial or dorsalis pedis arteries at the
ankle consistent with adequate flow in the foot (biphasic or triphasic)
Transcutaneous oxygen pressure > 40 mmHg
• Have an ulcer area at screening (on Day 14) as follows for the index ulcer:
1−5 cm2 for Cohorts A, B, C
2−5 cm2 for Cohort D
• Have infection status of the index ulcer (per IDSA 2012 Guidelines) at the end of the run-in as follows:
No infection for Cohorts A and B
Mild infection for Cohorts C and D
• Have an index ulcer as follows:
Present for > 4 but ≤ 52 weeks at the initial screening visit
Located below the malleoli on the plantar or dorsal surface of the forefoot or midfoot
Extends into the dermis or SC tissue without evidence of exposed muscle,
tendon, bone, or joint capsule
• Able to comply with the study protocol, in the investigator’s judgment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a method of contraception having a failure rate of 1 year but Exclusion criteria:
• Have an index ulcer that is as follows (as determined by the investigator or
designated staff):
A decrease in surface area > 20% during the run-in from Day − 14 to Day 1
An increase in surface area > 20% during the run-in from Day − 14 to Day 1
Of non-diabetic pathophysiology
On the heel
Over an active/acute Charcot deformity
Over 5 cm on its longest dimension as measured on Day 14
With maximum depth >1cm on Day −14
With either positive probe to bone (PTB) test or positive foot X-Ray for osteomyelitis
Necrotic areas remaining after extensive sharp debridement at initial screening
Have moderate or severe index ulcer infection as defined by the IDSA/IWGDF classification at the screening visit or
any time prior to randomization
In cases where the patient has more than one foot ulcer, these criteria will not apply to any ulcer other than the index
ulcer.
• Have current evidence of osteomyelitis, cellulitis, or evidence of systemic infection including fever or pus drainage
from the index ulcer site at the screening visit or any time prior to dosing Have current evidence of osteomyelitis,
cellulitis, or evidence of systemic infection including fever or pus drainage from the index ulcer site at the
screening visit or any time prior to dosing
• Have gangrene present on any part of the affected foot
• Known PAD requiring revascularization
• Any significant edema in the foot with the index ulcer that may interfere with drug administration or ulcer
assessments in the judgment of the investigator
• Pregnant or lactating, or intending to become pregnant any time until 56 days
after the last dose of study drug
• Women of childbearing potential who have a positive serum pregnancy test
result at screening on Day 7 or a positive urine pregnancy test on Day 1
•Use of an investigational drug or participation in an investigational study within
30 days or 5 half-lives before administration of study drug, whichever is greater
• Have a glycated hemoglobin A1c (HbA1c_ level of > 12% assessed at screening
• Are currently receiving dialysis
• Are receiving oral or parenteral corticosteroids, immunosuppressive, or cytotoxic agents
• Positive Fecal Immunochemical Test (FIT) at screening
• Have active malignancy or any history of a malignancy
• First degree relative or two second-degree relatives with gastrointestinal (e.g.,
colorectal) cancer
• Have a known or suspected allergy to primary or secondary dressing materials
used in this trial
• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions
to chimeric, human, or humanized antibodies, fusion proteins, or murine
proteins or hypersensitivity to UTTR1147A (active drug substance) or any of the
excipients
• Has had or is currently undergoing, or is planning for, ulcer treatments with enzymes, growth factors, living skin,
dermal substitutes, or other advanced therapies, devices, or procedures
• Skin disorders that would in the opinion of the investigator, interfere with the
assessment or treatment of the index ulcer
• Skin lesion observed during examination that, in the investigator’s judgment, is
suspicious for malignancy unless fully evaluated by a dermatologist and deemed non-cancerous
• Planned procedure or surgery during the study
• Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or HIV antibody
• Illicit drug or alcohol abuse within 12 months prior to screening, in the opinion of
the investigator
• Any serious local or systemic infection requiring IV antibiotics within 3 months
prior to dosing, unless permitted by the Medical Monitor
•Current use of oral antibiotics for any reason other than mild infection of theindex ulcer at the time of screening
• Any serious medical condition or abnormality in clinical laboratory tests that, in
the investigator’s judgment, precludes the patient’s safe participation in and
completion of the study
• Donation or loss of whole blood (excluding the volume of blood that will be drawn during screening procedures) as
follows: 50−499 mL of whole blood within 30 days or >
499 mL of whole blood within 56 days prior to study drug administration
• History or presence of an abnormal electrocardiogram (ECG) that is clinically
significant in the investigator’s opinion, including complete left bundle branch
block, second- or third-degree heart block
• QT interval corrected using Fridericia’s formula (QTcF) > 440 ms demonstrated
by at least two ECGs > 30 minutes apart
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
• Active coronary artery disease (CAD) or major adverse cardiac event (MACE)
within the past 18 months
• Congestive Heart Failure greater than Class II

Principal Investigator for this trial: Dr Kamal Chokkalingam

Research Ethics Committee Reference: 16/EE/0040

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Correlates of sedentary behaviour and physical activity in Rheumatoid Arthritis (RA) and Osteoarthritis (OA)

Summary:
Moderate-to-vigorous physical activity (MVPA) is recommended for people with Rheumatoid Arthritis (RA) and lower
limb Osteoarthritis (OA) in order to improve physical and psychological health, as well as to reduce the joint pain,
disease-related inflammation, and associated physical dysfunction symptomatic of these conditions. However, the
physical dysfunction resulting from RA and OA also means that most individuals living with these conditions do not
engage in sufficient levels of MVPA to experience these health benefits.
Reducing sedentary behaviour (e.g., time spent sitting, lying) may be perceived as more manageable than increasing
MVPA for people with RA and OA. Recent studies in older adults have suggested that reducing sedentary behaviour
might help to improve physical function, enhance psychological health, and lessen systemic inflammation. Importantly,
the positive health benefits of reducing sedentary behaviour are reported to occur regardless of levels of MVPA
participation.
Currently, we know little about the physical and psychological health implications of sedentary behaviour for RA and
OA, as well as factors predictive of both sedentary time and MVPA engagement. In addition, we do not know if the
possible health implications of sedentary behaviour are independent from the health benefits of MVPA engagement for
these individuals.
The primary aim of this research is therefore to investigate (and compare) the determinants and health consequences
of objectively measured MVPA and sedentary behaviour in RA and OA. The research will be conducted at Russells Hall
Hospital (Dudley). Patients who consent will be asked to participate in 2 ‘study weeks’, 6 months apart. At the start and
end of each study week, participants will be asked to complete questionnaires, provide a fasted blood sample (RA
only), and undertake assessments of height, weight, body composition, and blood pressure. Participants will also be
given an accelerometer to wear for 7 days during the study week.

Inclusion criteria:
Rheumatoid Arthritis:
1. Patients must be clinically diagnosed with RA (ACR Clinical Classification Criteria; Aletaha et al., 2010).
2. Aged 18 years old and above.
Osteoarthritis:
1. Adults above 45 years of age.
2. Physician-made diagnosis of hip or knee OA regardless of radiographic evidence (confirmed by the consultant or
research nurse who will introduce the study to the participant).

Exclusion criteria:
Rheumatoid Arthritis:
1. Patients unable to ambulate independently, or with the use of a walking aid (e.g., walking stick)
2. Individuals will also be excluded if they have been diagnosed with fibromyalgia, gout, or lupus
3. Presence of any mental illness that causes significant memory loss, for example, Alzheimer’s disease and
vascular dementia
Osteoarthritis:
1. Patients unable to ambulate independently, or with the use of a support or aid (e.g., walking stick).
2. Co-existence of other forms of arthritis such as rheumatoid arthritis, fibromyalgia, gout, lupus (self-reported).
3. Individuals will also be excluded if they have been diagnosed with any mental illness that causes significant
memory loss (e.g., Alzheimer’s disease and vascular dementia [self-reported]).
Other exclusion criteria relevant to main protocol sub-section (RA only):
1. Cortisol awakening response – Patients taking corticosteroid treatment will be excluded from the section of the study
protocol that concerns assessment of the cortisol awakening response (i.e., saliva samples – corticosteroids will
interfere with hormone secretion/regulation and confound measurement of cortisol in saliva)

Principal Investigator for this trial: Dr A Abhishek

Research Ethics Committee Reference: 16/WM/0371

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GRAD – Can genomics predict dysphagia after head and neck radiotherapy?

Summary:
This study will assess the feasibility of biomarker studies that can identify head and neck (HN) cancer patients at high
risk of developing severe complications following radiotherapy or chemoradiotherapy. Some patients develop severe
complications including difficulty with swallowing, limited mouth opening and ORN – osteoradionecrosis (irreversible
damage to bone) while others who have had the same treatment do not. Radiation damage can reduce quality of life
and or cause early death. Although previous research suggests that genetic variations may be associated with postradiation
tissue damage (radiotoxicity), we currently have no means of predicting how individual patients will react to
radiation. If we could identify patients with high radiotoxicity risk, their treatments could be modified by using surgery as
the primary treatment, by using novel targeted therapies that are directed at cancer cells only or by reducing the
radiation dosage to tissues involved in swallowing.
Genome wide association studies (GWAS) search for small genetic variations, called single nucleotide
polymorphisms (SNPs) that occur more frequently in people with a particular characteristic than in people without. We
will use GWAS look at thousands of SNPs at the same time.
HN cancer patients who have completed their primary radiotherapy or chemoradiotherapy treatment within the last 1 to
5 years will be eligible to participate. Patients who have had HN surgery are ineligible. Consenting patients will be
asked to complete a short swallowing function questionnaire and record whether they have limited mouth opening,
tube feeding or have suffered from ORN post treatment. The 100 patients with the most severe swallowing problems
and 100 with minimal problems will be asked to attend a research clinic to provide saliva and blood samples for
GWAS. If new genetic associations are identified, researchers can use this information to inform further gene specific
radiotoxicity studies in the future.

Inclusion criteria:
Patients who have been treated for first head and neck cancer with radiotherapy or chemoradiotherapy
Patients who are between 1 and 5 years post treatment

Exclusion criteria:
Those patients not deemed able to give informed consent
Patients who have had laryngeal cancer
Patients who have had thyroid cancer
Patients who have had head and neck surgery

Principal Investigator for this trial: Dr Judith Christian

Research Ethics Committee Reference: 14/LO/0429

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A PHASE Ib, BLINDED, RANDOMIZED,MULTICENTER, MULTIPLE-ASCENDING DOSESTUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF UTTR1147A ADMINISTERED BY SUBCUTANEOUS INJECTION IN PATIENTS WITHNON-HEALING NEUROPATHIC DIABETIC FOOTULCERS

Summary:
Ulceration of the foot associated with diabetes mellitus is a common and disabling condition. Besides control of the
underlying diabetes, the current best standard of care (SOC) for Diabetic Foot Ulcers (DFUs) includes local ulcer care
with frequent cleaning and debridement, (removal of dead and hard skin, usually with a scalpel) control of any
infection, pressure-relieving strategies, and restoration of blood flow to the foot if needed.
The aim of this study is to test the safety of study drug UTTR1147A at different dose levels. UTTR1147A is a version of
a protein called interleukin-22 which helps to fight infection and repair tissue damage by encouraging the growth of
new tissue. There is currently only one ongoing study of UTTR1147A in healthy volunteers. Because the results are
blinded, not all of the side effects of this treatment are known.
This study is sponsored by Genentech Inc. About 66 – 90 patients, will take part in this double blind placebo
controlled study at approximately 15 sites in Europe. There will be at least 18 study visits if the patient’s ulcer remains
open through the duration of treatment. If the patient’s ulcer is still open at the end of the treatment period, the patient
will be followed weekly and SOC ulcer treatment will continue for 8 weeks in the observation period. If an ulcer is
confirmed closed at any time during the study, the patient may be followed every 4 weeks during the observation
period. Procedures involved include a physical examination, vital signs (pulse and blood pressure), blood tests,
ECGs, a foot X-Ray, tests for blood flow to the affected foot and DFU related assessments.
Based on the patient’s status of their DFU at the end of the 2-week run-in period (infected or not), patients will be
randomly assigned to one of 4 treatment cohorts (A. B, C or D) to receive either UTTR1147A or placebo. Cohorts A, B,
or D, will have a 2 to 1 chance of being treated with UTTR1147A. Group C have an equal chance of receiving either
UTTR1147A or placebo. Patients in Cohort D will undergo small biopsies from the edge of the ulcer in addition.
Neither the participant nor the study doctor will know what treatment was assigned.

Inclusion criteria:
• Signed Informed Consent Form
• Age ≥ 18 to ≤ 80 years
• Up to date on all age-appropriate cancer screenings per local standards or, if
not up to date or not sure about their status, document their understanding of the possible tumor-promoting risks of
UTTR1147A
• Have a diagnosis of Type 1 or Type 2 diabetes. Diagnosis may be established by medical records and history of
treatment or HbA1c ≥ 6.5%.
• Peripheral neuropathy that is confirmed by demonstrating loss of sensation with
use of a 10 g (5.07 Semmes-Weinstein) monofilament (IWGDF 2015)
• Have adequate circulation to the foot as documented by an Ankle Brachial
Index (ABI) > 0.7 AND at least one of the following:
Toe Brachial Index (TBI) ≥ 0.50
Doppler waveform in the posterior tibial or dorsalis pedis arteries at the
ankle consistent with adequate flow in the foot (biphasic or triphasic)
Transcutaneous oxygen pressure > 40 mmHg
• Have an ulcer area at screening (on Day 14) as follows for the index ulcer:
1−5 cm2 for Cohorts A, B, C
2−5 cm2 for Cohort D
• Have infection status of the index ulcer (per IDSA 2012 Guidelines) at the end of the run-in as follows:
No infection for Cohorts A and B
Mild infection for Cohorts C and D
• Have an index ulcer as follows:
Present for > 4 but ≤ 52 weeks at the initial screening visit
Located below the malleoli on the plantar or dorsal surface of the forefoot or midfoot
Extends into the dermis or SC tissue without evidence of exposed muscle,
tendon, bone, or joint capsule
• Able to comply with the study protocol, in the investigator’s judgment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a method of contraception having a failure rate of 1 year but Exclusion criteria:
• Have an index ulcer that is as follows (as determined by the investigator or
designated staff):
A decrease in surface area > 20% during the run-in from Day − 14 to Day 1
An increase in surface area > 20% during the run-in from Day − 14 to Day 1
Of non-diabetic pathophysiology
On the heel
Over an active/acute Charcot deformity
Over 5 cm on its longest dimension as measured on Day 14
With maximum depth >1cm on Day −14
With either positive probe to bone (PTB) test or positive foot X-Ray for osteomyelitis
Necrotic areas remaining after extensive sharp debridement at initial screening
Have moderate or severe index ulcer infection as defined by the IDSA/IWGDF classification at the screening visit or
any time prior to randomization
In cases where the patient has more than one foot ulcer, these criteria will not apply to any ulcer other than the index
ulcer.
• Have current evidence of osteomyelitis, cellulitis, or evidence of systemic infection including fever or pus drainage
from the index ulcer site at the screening visit or any time prior to dosing Have current evidence of osteomyelitis,
cellulitis, or evidence of systemic infection including fever or pus drainage from the index ulcer site at the
screening visit or any time prior to dosing
• Have gangrene present on any part of the affected foot
• Known PAD requiring revascularization
• Any significant edema in the foot with the index ulcer that may interfere with drug administration or ulcer
assessments in the judgment of the investigator
• Pregnant or lactating, or intending to become pregnant any time until 56 days
after the last dose of study drug
• Women of childbearing potential who have a positive serum pregnancy test
result at screening on Day 7 or a positive urine pregnancy test on Day 1
•Use of an investigational drug or participation in an investigational study within
30 days or 5 half-lives before administration of study drug, whichever is greater
• Have a glycated hemoglobin A1c (HbA1c_ level of > 12% assessed at screening
• Are currently receiving dialysis
• Are receiving oral or parenteral corticosteroids, immunosuppressive, or cytotoxic agents
• Positive Fecal Immunochemical Test (FIT) at screening
• Have active malignancy or any history of a malignancy
• First degree relative or two second-degree relatives with gastrointestinal (e.g.,
colorectal) cancer
• Have a known or suspected allergy to primary or secondary dressing materials
used in this trial
• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions
to chimeric, human, or humanized antibodies, fusion proteins, or murine
proteins or hypersensitivity to UTTR1147A (active drug substance) or any of the
excipients
• Has had or is currently undergoing, or is planning for, ulcer treatments with enzymes, growth factors, living skin,
dermal substitutes, or other advanced therapies, devices, or procedures
• Skin disorders that would in the opinion of the investigator, interfere with the
assessment or treatment of the index ulcer
• Skin lesion observed during examination that, in the investigator’s judgment, is
suspicious for malignancy unless fully evaluated by a dermatologist and deemed non-cancerous
• Planned procedure or surgery during the study
• Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or HIV antibody
• Illicit drug or alcohol abuse within 12 months prior to screening, in the opinion of
the investigator
• Any serious local or systemic infection requiring IV antibiotics within 3 months
prior to dosing, unless permitted by the Medical Monitor
•Current use of oral antibiotics for any reason other than mild infection of theindex ulcer at the time of screening
• Any serious medical condition or abnormality in clinical laboratory tests that, in
the investigator’s judgment, precludes the patient’s safe participation in and
completion of the study
• Donation or loss of whole blood (excluding the volume of blood that will be drawn during screening procedures) as
follows: 50−499 mL of whole blood within 30 days or >
499 mL of whole blood within 56 days prior to study drug administration
• History or presence of an abnormal electrocardiogram (ECG) that is clinically
significant in the investigator’s opinion, including complete left bundle branch
block, second- or third-degree heart block
• QT interval corrected using Fridericia’s formula (QTcF) > 440 ms demonstrated
by at least two ECGs > 30 minutes apart
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
• Active coronary artery disease (CAD) or major adverse cardiac event (MACE)
within the past 18 months
• Congestive Heart Failure greater than Class II

Principal Investigator for this trial: Dr Kamal Chokkalingam

Research Ethics Committee Reference: 16/EE/0040

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Study to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease

Summary:
Crohn’s disease is a long-term condition that causes inflammation of the lining of the digestive system. Inflammation can affect any part of the digestive system, but most commonly occurs in the last section of the small intestine or the large intestine.
The purpose of part I of the study is to see if JNJ 6430450, the study drug is useful for treating patients with moderately to severely active Crohn’s Disease. The study is also done to see if JNJ-64304500, is safe to take without causing too many side effects. In addition to this the purpose of Part II is to find the dose of JNJ 64304500 that best treats moderately to severely active Crohn’s Disease and to understand patient responses to Crohn’s diseases treatments
using an approved drug called ustekinumab.
This is double-blinded study meaning that neither the participant and the study doctor will know which medication is
being given. The study is randomised, meaning that participants will be randomly assigned to receive either JNJ-
64304500, or placebo in part 1 or JNJ-64304500, placebo or ustekinumab in part II.
Janssen Research & Development, LLC is the sponsor of this study which will take place worldwide. It is anticipated that approximately 200 participants will be enrolled in Part I and an additional 250 participants will be enrolled in Part II.

Inclusion criteria:
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Be a man or woman >18 years of age.
2. Have Crohn’s disease or fistulising Crohn’s disease of at least 3 months’ duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
3. Have active Crohn’s disease, defined as a baseline CDAI score of >220 but 0.3 mg/dL [>3.0 mg/L])
OR
b. Calprotectin >250 mg/kg.
5. In Part I, meet the following requirements for prior or current medications for Crohn’s disease:
a. Has previously demonstrated inadequate response, loss of response, or intolerance to 1 or more approved biologic
therapies (eg, infliximab, adalimumab, certolizumab pegol, or vedolizumab) as outlined in Attachment 1 of the protocol.
OR
b. Has failed conventional therapy:
1) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, 6-MP, or
MTX) at adequate therapeutic doses.
OR
2) Has a history of failure to respond to or tolerate an adequate course of
corticosteroids and/or immunomodulators (ie, AZA, 6-MP, or MTX)
OR
3) Is corticosteroid dependent or has had a history of corticosteroid dependency.
6. In Part II, meet the following requirement for prior or current medications for Crohn’s disease: has previously
demonstrated inadequate response, loss of response, or intolerance to 1 or more approved biologic therapies (eg,
infliximab, adalimumab, certolizumab pegol, or vedolizumab) as outlined in Attachment 1 of the protocol.
7. Adhere to the following requirements for concomitant medication for the treatment of Crohn’s disease, which are
permitted provided that doses meeting these requirements are stable, or have been discontinued, for at least 3 weeks
before baseline (Week 0), unless otherwise specified:
a. Oral 5-aminosalicylic acid (5-ASA) compounds.
b. Oral corticosteroids at a prednisone-equivalent dose at or below 40 mg/day, or 9 mg/day of budesonide, or 5 mg/day
beclomethasone dipropionate.
c. Antibiotics being used as a primary treatment of Crohn’s disease.
d. Conventional immunomodulators (ie, AZA, 6-MP, or MTX):participants must have been
taking them for at least 12 weeks and at a stable dose for at least 4 weeks before
baseline.
8. A participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50
years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during
screening). Adenomatous polyps must be removed before the first administration of study agent.
9. A participant who has had extensive colitis for ≥8 years, or disease limited to the left side of the colon for ≥12 years,
must either have had a colonoscopy to assess for the presence of dysplasia within 1 year before the first
administration of study agent or a colonoscopy to assess for the presence of malignancy at the screening visit, with no
evidence of malignancy
10. Have screening laboratory test results within the following parameters:
a. Haemoglobin ≥8.0 g/dL.
b. White blood cell count (WBCs) ≥3.0 × 103/μL.
c. Neutrophils ≥1.5 × 103/μL.
d. Platelets ≥100 × 103/μL.
e. Serum creatinine Exclusion criteria:
Any potential participants who meets any of the following criteria will be excluded from participating
in the study:
1. Has complications of Crohn’s disease such as symptomatic strictures or stenoses, short gut syndrome, or any
other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess
response to therapy, or would possibly confound the ability to assess the effect of treatment with JNJ-64304500 or
ustekinumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary
if drained and adequately treated at least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal
abscesses, provided that there is no anticipated need for any further surgery. Participants with active fistulas may be
included if there is no anticipation of a need for surgery and there are currently no abscesses identified.
3. Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before
baseline.
4. Has a draining (ie, functioning) stoma or ostomy.
5. Has received any of the following prescribed medications or therapies within the specified period:
a. IV corticosteroids Principal Investigator for this trial: Dr Gordon Moran

Research Ethics Committee Reference: 16/EE/0356

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The SCOTTY Study – whole genome sequencing study of young colon cancer patients and their parents.

Summary:
Cancer of the large bowel (colorectal cancer) is common in the general population and the lifetime risk for someone living in the UK is 1 in 17. Whilst modern surgery, radiotherapy and chemotherapy treatments have impacted beneficially on survival outcome, many patients still die from their disease. Hence, there is a pressing need to understand the causes of colorectal cancer and to intervene early. Colorectal cancer under the age of 40 years of age is particularly rare, with less than 1.2% of all cases aged Inclusion criteria:
PATIENT INCLUSION CRITERIA

•Patients who have developed colorectal cancer at aged 40 years of age or younger at the time of diagnosis.
(Individuals OVER the age of 40 years ARE eligible if they were previously diagnosed with colorectal cancer when aged 40 years or younger).

•Patients will not have a known molecular genetic predisposition to the development of colorectal cancer or a strong family history of cancer consistent with known dominant disorders.

•Patients are able to provide written informed consent for whole genome sequencing and blood/saliva biomarkers.

•Documentary evidence of a pathologically confirmed adenocarcinoma of colon or rectum along with consent to access archived tumour material from the time of operation.

•Demographic and drug history are available or can be ascertained from patient.

•If the patient is under the age of 16 years, both parents are available to sign/countersign a consent form. Whilst
cases under the age of 16 years are extremely rare, these cases greatly enhance the value of their contribution to the study.

•Inclusion can be from any part of mainland GB and Northern Ireland and of any ancestry.

•Patients will be asked if they agree to being re-contacted if further confirmatory samples are required and/or results are of clinically significant relevance.

PARENTS INLCUSION CRITERIA

•Neither parent will have had a past or present diagnosis of colorectal cancer or other cancer relevant to CRC
predisposition such as endometrial cancer.

•Both parents will be alive and are contactable within the United Kingdom and Northern Ireland.

•Both parents will not have a known genetic predisposition to the development of colon cancer.

•Both parents will be able to provide written informed consent for sampling.

•Both parents will provide a simple blood sample for whole genome sequencing & blood or saliva biomarkers.

•Demographic and drug history are available or can be ascertained from parents.

•Both parents will be asked to agree to being re-contacted if further confirmatory samples are required and/or results have clinical implications.

Exclusion criteria:
– BOTH parents unable to provide samples.
– The inability to provide informed consent.
– Patients who have developed CRC aged over 40 years at diagnosis.
– Tumour that has shown loss of DNA mismatch repair gene protein expression or tumour that has exhibited MSI (micro satellite instability).
– Familial CRC (a strong family history)

Exclusion criteria – PARENTS

– Both parents are unable to provide samples.
– The inability to provide informed consent.

– Known mutations in colorectal susceptibility genes within the family (eg APC,MLH1, MSH2, MSH6, PMS2, MUTYH, POLE1, POLD1, SMAD4/BRCA/STK11).

Principal Investigator for this trial: Dr Abhijit Dixit

Research Ethics Committee Reference: 16/SS/0082

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Defining the evidence base for health care delivery in congenital adrenal hyperplasia – a multi-centre CAH-UK (Children & Adolescents with CAH in the UK) initiative)

Summary:
Congenital Adrenal Hyperplasia (CAH) is associated with significant morbidity and mortality and occurs in about 1 in 10,000 life-births (about 6,300 individuals in the UK). Recent clinical data suggest impaired heath in young adults with CAH. The onset of such problems during childhood remains unclear. However, it is of paramount importance to define an evidence base to develop strategies for secondary prevention of future health problems. To define novel predictive markers of long-term health problems, we have formed a clinical consortium (CAH-UK) involving 16 tertiary UK centres to explore the current health status in 8 to 18 year olds with CAH. We have designed a cross-sectional study to define the current health in children and young people with CAH in the UK. These patients undergo there to six monthly blood tests as part of the routine clinical care. We have planned to add on additional blood, urine and saliva collections to devise novel test and explore the metabolic status. In addition, we will for the first time define if quality of life is already altered at this young age as it is in young adults. We will establish the presence and onset of potential health problems in children and young persons with CAH in the UK. Study participants will have an immediate benefit from this study as their therapy can be individualised. After validation novel markers of disease control will be implemented into clinical practice within the next 2-3 years improving personalisation of treatment in all patients with CAH. The identification of altered health related quality of life would aid developing care strategies. This combination of investigations represents a major step towards a personalised therapeutic approach in CAH.

Inclusion criteria:
Patients with CAH
1) Patients with known CAH due to 21-hydroxylase deficiency confirmed by hormonal and/ or genetic testing
2) Aged 8 – 18 years
3) Participants must have capacity to assent/consent and provide a signed and dated informed consent.

Controls
a) Aged 8 – 18 years
b) Participants must have capacity to assent/consent and provide a signed and dated informed consent.

Exclusion criteria:
Patients with CAH
1) Pregnancy

Controls
1) Past or present history of an endocrinopathy (all stages)
2) Type 1, diabetes, Type 2 diabetes, Insulin resistance
3) Known conditions of lipid/ cholesterol metabolism
4) Presence of any psychiatric disorder
5) Current or past use of psychiatric medication
6) Glucocorticoid use within the last 6 months
7) Diagnosed learning difficulties and/or full-scale IQ Principal Investigator for this trial: Dr Tabitha Randell

Research Ethics Committee Reference: 15/YH/0537

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A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF MONGERSEN (GED-0301) FOR THE TREATMENT OF SUBJECTS WITH ACTIVE CROHN’S DISEASE

Summary:
The purpose of this study is to determine whether GED-0301, is a safe, effective and tolerable treatment for patients with active Crohn’s Disease (CD).
GED-0301 is an experimental drug which means it has not been approved by the health authorities for treatment of Crohn’s Disease. GED-0301 and placebo are administered orally by tablet.
The screening period is up to 28 days during which patient eligibility will be determined. After screening the study will be divided into 3 treatment groups and 1 placebo.
Group 1 will receive GED-0301 160 mg once daily for 12 weeks; followed by placebo once daily for 4 weeks; followed by alternating GED-0301 160 mg once daily for 4 weeks and placebo once daily for 4 weeks, until the Week 52 Visit; Group 2 subjects will receive GED-0301 160 mg once daily for 12 weeks; followed by placebo once daily for 4 weeks; followed by alternating GED-0301 40 mg once daily for 4 weeks and placebo once daily for 4 weeks, until the Week 52 Visit.
Group 3 subjects will receive GED-0301 160 mg once daily for 12 weeks; followed by continuous GED-0301 40 mg once daily, until the Week 52 Visit.
Group 4 will receive Placebo once daily until the Week 52 Visit.

The study duration, will be up to 60 weeks (4 weeks in the Screening Period, 52 weeks in the Double-blind Treatment Period, 4 weeks in the Follow-up Period). The total length of the treatment period will be 52 weeks.
If eligible patients can opt to go into the Long-term Active- treatment Study after week 12 up until week 52 The End of Study is defined as the date of the last visit of the last subject to complete the post-treatment follow-up.

Overall approximately 1064 patients will be recruited from approximately 512 sites worldwide.

Inclusion criteria:
The key inclusion criteria for this study are as follows:
Diagnosis of CD with a duration of at least 3 months prior to the Screening Visit
Diagnosis of ileitis, ileocolitis or colitis, as determined by endoscopic, radiographic or any other imaging modality (eg, magnetic resonance imaging [MRI], computed tomography [CT] scan)
Active disease, defined as a CDAI score ≥ 220 and ≤ 450 at screening
Subject must have a 7-day average stool frequency ≥ 3.5 or abdominal pain ≥ 1.5 at screening.
Subject must have a total SES-CD ≥ 6 at screening, or the ileum segmental SES-CD ≥ 4 at screening
Must have failed or experienced intolerance to at least one of the following:
aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]); or biologics for the treatment of CD

Exclusion criteria:
The key exclusion criteria for this study are as follows:
Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or
diverticular disease-associated colitis
Subject has local manifestations of CD such as strictures, abscesses, short bowel syndrome; or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy
Subject had any intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit
Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit
Use of intravenous (IV) corticosteroids within 2 weeks prior to the Screening Visit
Use of topical treatment such as 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit
Use of cholestyramine within 3 weeks prior to the Screening Visit
Prior treatment with more than 3 biologics for the treatment of CD
Treatment with a biologic within 8 weeks prior to the Screening Visit
Prior treatment with natalizumab

Principal Investigator for this trial: Dr Gordon Moran

Research Ethics Committee Reference: 16/ES/0001

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A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF MONGERSEN (GED-0301) FOR THE TREATMENT OF SUBJECTS WITH ACTIVE CROHN’S DISEASE

Summary:
The purpose of this study is to determine whether GED-0301, is a safe, effective and tolerable treatment for patients with active Crohn’s Disease (CD).
GED-0301 is an experimental drug which means it has not been approved by the health authorities for treatment of Crohn’s Disease. GED-0301 and placebo are administered orally by tablet.
The screening period is up to 28 days during which patient eligibility will be determined. After screening the study will be divided into 3 treatment groups and 1 placebo.
Group 1 will receive GED-0301 160 mg once daily for 12 weeks; followed by placebo once daily for 4 weeks; followed by alternating GED-0301 160 mg once daily for 4 weeks and placebo once daily for 4 weeks, until the Week 52 Visit; Group 2 subjects will receive GED-0301 160 mg once daily for 12 weeks; followed by placebo once daily for 4 weeks; followed by alternating GED-0301 40 mg once daily for 4 weeks and placebo once daily for 4 weeks, until the Week 52 Visit.
Group 3 subjects will receive GED-0301 160 mg once daily for 12 weeks; followed by continuous GED-0301 40 mg once daily, until the Week 52 Visit.
Group 4 will receive Placebo once daily until the Week 52 Visit.

The study duration, will be up to 60 weeks (4 weeks in the Screening Period, 52 weeks in the Double-blind Treatment Period, 4 weeks in the Follow-up Period). The total length of the treatment period will be 52 weeks.
If eligible patients can opt to go into the Long-term Active- treatment Study after week 12 up until week 52 The End of Study is defined as the date of the last visit of the last subject to complete the post-treatment follow-up.

Overall approximately 1064 patients will be recruited from approximately 512 sites worldwide.

Inclusion criteria:
The key inclusion criteria for this study are as follows:
Diagnosis of CD with a duration of at least 3 months prior to the Screening Visit
Diagnosis of ileitis, ileocolitis or colitis, as determined by endoscopic, radiographic or any other imaging modality (eg, magnetic resonance imaging [MRI], computed tomography [CT] scan)
Active disease, defined as a CDAI score ≥ 220 and ≤ 450 at screening
Subject must have a 7-day average stool frequency ≥ 3.5 or abdominal pain ≥ 1.5 at screening.
Subject must have a total SES-CD ≥ 6 at screening, or the ileum segmental SES-CD ≥ 4 at screening
Must have failed or experienced intolerance to at least one of the following:
aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]); or biologics for the treatment of CD

Exclusion criteria:
The key exclusion criteria for this study are as follows:
Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or
diverticular disease-associated colitis
Subject has local manifestations of CD such as strictures, abscesses, short bowel syndrome; or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy
Subject had any intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit
Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit
Use of intravenous (IV) corticosteroids within 2 weeks prior to the Screening Visit
Use of topical treatment such as 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit
Use of cholestyramine within 3 weeks prior to the Screening Visit
Prior treatment with more than 3 biologics for the treatment of CD
Treatment with a biologic within 8 weeks prior to the Screening Visit
Prior treatment with natalizumab

Principal Investigator for this trial: Dr Gordon Moran

Research Ethics Committee Reference: 16/ES/0001

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Genome-wide association study of developmental dysplasia of the hip in children and adolescents Synopsis

Summary:
We seek to find out whether variation in DNA sequences is associated with the onset of developmental dysplasia of the hip (DDH) in infants and children (age 1 week to 17 years).
DDH is the most common congenital musculoskeletal anomaly in the UK and its etiology remains unknown. The term “developmental” dysplasia replaced the older term “congenital” dysplasia because infants can reveal normal hips at birth with the dysplasia developing subsequently. Successful identification of robust genetic risk factors may provide important insight into the molecular mechanisms in DDH, which could offer new treatment, or biomarkers for screening of atrisk
groups.

To achieve this goal we will perform genomewide
association analyses using DNA collected from patients
ascertained through a network of UK orthopaedic services. DNA sample will be taken by either saliva sample or blood sample. We will obtain 200 μl of blood in acid citrate dextrose preservative for those admitted for hip surgery. We will collect saliva by swabs into Oragen® kits in the remaining patients. Samples will be stored on site and periodically shipped to Newcastle University for processing. No other procedures will be performed as part of this study.We will also use (a) information from images (X-rays or ultrasound scans) taken for routine clinical care and (b) information from the case notes (medical records) such as demographic data or data about ethnicity.

This study is the unmatched case-control study lasting 4 years. Infants and children ≤18 years with firm DDH diagnosis and without underlying musculo skeletal or disorder are eligible to take part in this research. Patients will be recruited from 6 sites including Great Ormond Street Hospital, Nuffield Orthopaedics NHS Trust, Barts and The London NHS Trust, Addenbrook’s Hospital Cambridge University, Southampton General Hospital and Evelina Children’s Hospital.

Inclusion criteria:
1. Patients with a diagnosis of DDH based on clinical and imaging findings and established by the sitespecific
investigator
2. Patients with previous operative or nonoperative
treatment for DDH

Exclusion criteria:
Patients with neurological diagnoses, metabolic disorders, and skeletal dysplasias (nonDDH).

Principal Investigator for this trial: Ms Kathryn Price

Research Ethics Committee Reference: 11/LO/1540

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Genome-wide association study of developmental dysplasia of the hip in children and adolescents Synopsis

Summary:
We seek to find out whether variation in DNA sequences is associated with the onset of developmental dysplasia of the hip (DDH) in infants and children (age 1 week to 17 years).
DDH is the most common congenital musculoskeletal anomaly in the UK and its etiology remains unknown. The term “developmental” dysplasia replaced the older term “congenital” dysplasia because infants can reveal normal hips at birth with the dysplasia developing subsequently. Successful identification of robust genetic risk factors may provide important insight into the molecular mechanisms in DDH, which could offer new treatment, or biomarkers for screening of atrisk
groups.

To achieve this goal we will perform genomewide
association analyses using DNA collected from patients
ascertained through a network of UK orthopaedic services. DNA sample will be taken by either saliva sample or blood sample. We will obtain 200 μl of blood in acid citrate dextrose preservative for those admitted for hip surgery. We will collect saliva by swabs into Oragen® kits in the remaining patients. Samples will be stored on site and periodically shipped to Newcastle University for processing. No other procedures will be performed as part of this study.We will also use (a) information from images (X-rays or ultrasound scans) taken for routine clinical care and (b) information from the case notes (medical records) such as demographic data or data about ethnicity.

This study is the unmatched case-control study lasting 4 years. Infants and children ≤18 years with firm DDH diagnosis and without underlying musculo skeletal or disorder are eligible to take part in this research. Patients will be recruited from 6 sites including Great Ormond Street Hospital, Nuffield Orthopaedics NHS Trust, Barts and The London NHS Trust, Addenbrook’s Hospital Cambridge University, Southampton General Hospital and Evelina Children’s Hospital.

Inclusion criteria:
1. Patients with a diagnosis of DDH based on clinical and imaging findings and established by the sitespecific
investigator
2. Patients with previous operative or nonoperative
treatment for DDH

Exclusion criteria:
Patients with neurological diagnoses, metabolic disorders, and skeletal dysplasias (nonDDH).

Principal Investigator for this trial: Ms Kathryn Price

Research Ethics Committee Reference: 11/LO/1540

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Phenotypic and Genotypic Characteristics of Paediatric Myelodysplastic Syndromes

Summary:
This research project will study a group of rare blood disorders in children, called Paediatric Myelodysplastic
Syndromes (MDS).Paediatric MDS is characterised by failure of normal blood cells production. Without treatment these syndromes are usually fatal and can lead to leukaemia. The aim of this project is to improve our current understanding of the molecular pathways that lead to the disease development;identify all the disease related genetic abnormalities;document the natural history of the disease;create correlations between the clinical presentations and genetic defects and create targets for future therapies. Children with a diagnosis of Paediatric MDS from across all specialist paediatric haematology centres in the UK will be invited to participate in this project. From the study of these
cases we aim to built a comprehensive picture of paediatric MDS,which is something that has not been achieved so far. We will record how these disorders present, all their clinical characteristics; laboratory tests results, how the disorders progress with time and the response of the different subgroups of patients to the current treatments. The samples collected will be in the form of blood,bone marrow,nail clippings,skin biopsies, saliva and hair follicles. These samples will be tested for all genetic abnormalities that have been previously described in different types of MDS. In cases that no known genetic abnormality is detected, further genetic testing(called whole genome sequencing) will be performed, after appropriate consent, in order to identify new genetic defects linked with MDS. This will enable us to provide an accurate diagnosis for each family, but also to select the most appropriate treatment for each case. We will study the behaviour of blood cells from children with MDS,using state-of-the-art technology,with the objective to identify the molecular pathways that lead to the disease development. This will allow us to identify the cell that the disease originates and target this in the future.

Inclusion criteria:
1. Age from birth to 21 years
2. Probable diagnosis of MDS ie
a. Sustained (>3 months) unexplained cytopenia
b. Bi/trilineage morphological myelodysplasia
c. Acquired clonal cytogenetic abnormality in haematopoietic cells
d. Bone marrow blasts >5%
3. Children with syndromic MDS or suspected syndromic MDS
4. Children with secondary MDS: chemotherapy, radiotherapy, toxic agents
5. Children with IBMFS and features of myelodysplasia
6. Children with suspected familial MDS
7. Denovo MDS (hypocellular or hypercellular )
8. Juvenile Myelomonocytic Leukaemia
9. MDS/MPS
10. MDS with systemic disease
11. Children with Downs MDS

Exclusion criteria:
1. Patients who do not fulfil inclusion criteria
2. Patients who have not consented for the study
3. Children with known CBF AML translocations

Principal Investigator for this trial: Dr Simone Stokley

Research Ethics Committee Reference: 15/LO/0961

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Phenotypic and Genotypic Characteristics of Paediatric Myelodysplastic Syndromes

Summary:
This research project will study a group of rare blood disorders in children, called Paediatric Myelodysplastic
Syndromes (MDS).Paediatric MDS is characterised by failure of normal blood cells production. Without treatment these syndromes are usually fatal and can lead to leukaemia. The aim of this project is to improve our current understanding of the molecular pathways that lead to the disease development;identify all the disease related genetic abnormalities;document the natural history of the disease;create correlations between the clinical presentations and genetic defects and create targets for future therapies. Children with a diagnosis of Paediatric MDS from across all specialist paediatric haematology centres in the UK will be invited to participate in this project. From the study of these
cases we aim to built a comprehensive picture of paediatric MDS,which is something that has not been achieved so far. We will record how these disorders present, all their clinical characteristics; laboratory tests results, how the disorders progress with time and the response of the different subgroups of patients to the current treatments. The samples collected will be in the form of blood,bone marrow,nail clippings,skin biopsies, saliva and hair follicles. These samples will be tested for all genetic abnormalities that have been previously described in different types of MDS. In cases that no known genetic abnormality is detected, further genetic testing(called whole genome sequencing) will be performed, after appropriate consent, in order to identify new genetic defects linked with MDS. This will enable us to provide an accurate diagnosis for each family, but also to select the most appropriate treatment for each case. We will study the behaviour of blood cells from children with MDS,using state-of-the-art technology,with the objective to identify the molecular pathways that lead to the disease development. This will allow us to identify the cell that the disease originates and target this in the future.

Inclusion criteria:
1. Age from birth to 21 years
2. Probable diagnosis of MDS ie
a. Sustained (>3 months) unexplained cytopenia
b. Bi/trilineage morphological myelodysplasia
c. Acquired clonal cytogenetic abnormality in haematopoietic cells
d. Bone marrow blasts >5%
3. Children with syndromic MDS or suspected syndromic MDS
4. Children with secondary MDS: chemotherapy, radiotherapy, toxic agents
5. Children with IBMFS and features of myelodysplasia
6. Children with suspected familial MDS
7. Denovo MDS (hypocellular or hypercellular )
8. Juvenile Myelomonocytic Leukaemia
9. MDS/MPS
10. MDS with systemic disease
11. Children with Downs MDS

Exclusion criteria:
1. Patients who do not fulfil inclusion criteria
2. Patients who have not consented for the study
3. Children with known CBF AML translocations

Principal Investigator for this trial: Dr Simone Stokley

Research Ethics Committee Reference: 15/LO/0961

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

CANcer DIagnosis Decision rules

Summary:
In primary care the key areas of concern for both doctor and patients are delay in diagnosing cancer, getting high risk patients referred first, and keeping investigation to a minimum. There have been few valid studies to assist decisionmaking
in primary care, either to get a patient referred quickly or to assist in making sure an anxious patient is
effectively reassured. This study seeks to work out which of the symptoms and examination findings are the most
effective in predicting lung or colon cancer. To decide the best clinical information to collect we will use information
from a separate study that will interview patients and get consensus from a group of experts. Then we will recruit
20,000 patients who consult their GP half
with lung symptoms and the other half with low bowel symptoms. Clinical
information will be collected using standardised internet based forms. Willing patients will complete lifestyle
questionnaires and provide blood or saliva samples (including for genetic analysis). The National Cancer Registry will
NHS R&D Form IRAS Version 3.4
5 85145/364607/14/448
Health Departments Research Ethics Service, this summary will be published on the website of the National Research
Ethics Service following the ethical review.
In primary care the key areas of concern for both doctor and patients are delay in diagnosing cancer, getting high risk
patients referred first, and keeping investigation to a minimum. There have been few valid studies to assist decision-making in primary care, either to get a patient referred quickly or to assist in making sure an anxious patient is effectively reassured. This study seeks to work out which of the symptoms and examination findings are the most effective in predicting lung or colon cancer. To decide the best clinical information to collect we will use information from a separate study that will interview patients and get consensus from a group of experts. Then we will recruit 20,000 patients who consult their GP half with lung symptoms and the other half with low bowel symptoms. Clinical information will be collected using standardised internet based forms. Willing patients will complete lifestyle questionnaires and provide blood or saliva samples (including for genetic analysis). The National Cancer Registry will
then be monitored and GP notes reviewed to see which patients develop cancer, and statistical analysis will determine the most important clinical variables that predict cancer. The clinical prediction ‘rules’ or decision aids developed from these studies will then be tested with a further 2000 patients for each condition for validity.

Inclusion criteria:
Possible Lung Cancer Patients:
Include: Adults > 35 years presenting with symptoms lasting for 3 weeks that could be associated with lung cancer – either focal chest symptoms (haemoptysis, dyspnoea, thoracic pain, cough) or systemic symptoms lasting for 3 weeks with no other localising symptoms (e.g. loss of appetite, loss of weight, fatigue)

Possible Colorectal Cancer Patients:
Include: Adults > 35 years (since colon cancer is very rarely diagnosed in the younger age group) presenting with lower gastrointestinal symptoms that could be associated with colorectal cancer. This includes any of the following symptoms: rectal bleeding, bowel symptoms (change in bowel habit, tenesmus, urgency, incomplete emptying, nocturnal symptoms) systemic symptoms (weight loss, anorexia, fatigue) lower abdominal pain.

Exclusion criteria:
Possible lung cancer patients:
Exclude: Known lung cancer, pregnancy, or urgent admission to hospital (e.g. massive haemoptysis), other terminal illness. Inability to provide a good history (severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment).
Possible colorectal patients:
Exclude:Known colorectal cancer, pregnancy, or urgent admission to hospital (massive bleeding or acute abdomen), other terminal illness. Inability to provide a good history (severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment).

Principal Investigator for this trial: Dr David R Baldwin

Research Ethics Committee Reference: 12/SC/0328

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

CANcer DIagnosis Decision rules

Summary:
In primary care the key areas of concern for both doctor and patients are delay in diagnosing cancer, getting high risk patients referred first, and keeping investigation to a minimum. There have been few valid studies to assist decisionmaking
in primary care, either to get a patient referred quickly or to assist in making sure an anxious patient is
effectively reassured. This study seeks to work out which of the symptoms and examination findings are the most
effective in predicting lung or colon cancer. To decide the best clinical information to collect we will use information
from a separate study that will interview patients and get consensus from a group of experts. Then we will recruit
20,000 patients who consult their GP half
with lung symptoms and the other half with low bowel symptoms. Clinical
information will be collected using standardised internet based forms. Willing patients will complete lifestyle
questionnaires and provide blood or saliva samples (including for genetic analysis). The National Cancer Registry will
NHS R&D Form IRAS Version 3.4
5 85145/364607/14/448
Health Departments Research Ethics Service, this summary will be published on the website of the National Research
Ethics Service following the ethical review.
In primary care the key areas of concern for both doctor and patients are delay in diagnosing cancer, getting high risk
patients referred first, and keeping investigation to a minimum. There have been few valid studies to assist decision-making in primary care, either to get a patient referred quickly or to assist in making sure an anxious patient is effectively reassured. This study seeks to work out which of the symptoms and examination findings are the most effective in predicting lung or colon cancer. To decide the best clinical information to collect we will use information from a separate study that will interview patients and get consensus from a group of experts. Then we will recruit 20,000 patients who consult their GP half with lung symptoms and the other half with low bowel symptoms. Clinical information will be collected using standardised internet based forms. Willing patients will complete lifestyle questionnaires and provide blood or saliva samples (including for genetic analysis). The National Cancer Registry will
then be monitored and GP notes reviewed to see which patients develop cancer, and statistical analysis will determine the most important clinical variables that predict cancer. The clinical prediction ‘rules’ or decision aids developed from these studies will then be tested with a further 2000 patients for each condition for validity.

Inclusion criteria:
Possible Lung Cancer Patients:
Include: Adults > 35 years presenting with symptoms lasting for 3 weeks that could be associated with lung cancer – either focal chest symptoms (haemoptysis, dyspnoea, thoracic pain, cough) or systemic symptoms lasting for 3 weeks with no other localising symptoms (e.g. loss of appetite, loss of weight, fatigue)

Possible Colorectal Cancer Patients:
Include: Adults > 35 years (since colon cancer is very rarely diagnosed in the younger age group) presenting with lower gastrointestinal symptoms that could be associated with colorectal cancer. This includes any of the following symptoms: rectal bleeding, bowel symptoms (change in bowel habit, tenesmus, urgency, incomplete emptying, nocturnal symptoms) systemic symptoms (weight loss, anorexia, fatigue) lower abdominal pain.

Exclusion criteria:
Possible lung cancer patients:
Exclude: Known lung cancer, pregnancy, or urgent admission to hospital (e.g. massive haemoptysis), other terminal illness. Inability to provide a good history (severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment).
Possible colorectal patients:
Exclude:Known colorectal cancer, pregnancy, or urgent admission to hospital (massive bleeding or acute abdomen), other terminal illness. Inability to provide a good history (severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment).

Principal Investigator for this trial: Dr David R Baldwin

Research Ethics Committee Reference: 12/SC/0328

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase III doubleblind placebocontrolled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumours.

Summary:
Add-Aspirin is a large clinical trial for people who have had treatment for breast, colorectal, gastro-oesophageal
or prostate cancer. The aim of the trial is to find out whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back.
Participants will self-administer 100mg aspirin once daily for 8 weeks. After 8 weeks, if taking regular aspirin does not cause any serious problems, participants will be randomly allocated to self-administer either a 300mg aspirin tablet, a 100mg aspirin tablet or a placebo tablet once daily for at least five years. Participants who are 75 years old or over, will only be allocated to 100mg aspirin tablets daily or placebo tablets. To ensure the results of the trial are as reliable as possible, neither the participants, nor the clinicians will know which tablets participants are allocated to.
In total, 9,920 participants will be randomised into the trial over 3 – 6 years (depending on tumour site). All participants will be followed-up within the trial for at least 5 years. In the UK, long-term follow-up data will also be obtained from routinely-collected healthcare databases.
A programme of associated correlative science is planned incorporating both short and long-term projects which will
investigate key questions including: determining the mechanism of action for an anti-cancer effect of aspirin;
determining biomarkers that identify participants most likely to experience serious aspirin-related toxicity; determining the roles of genotypic and phenotypic differences in aspirin’s actions; identifying individuals who will benefit most or least from aspirin and determining the mechanisms underlying potential non-cancer benefits of aspirin.

Inclusion criteria:
COMMON INCLUSION CRITERIA
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease
BREAST COHORT INCLUSION CRITERIA
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
a. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further
intervention) should be completed prior to registration
b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT)
a. Patients who have undergone breastconserving
surgery should receive adjuvant RT
b. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
c. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not)
receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
a. Node positive
b. Node negative with high-risk features -2 or more of:
i. ER negative
ii. HER2 positive
iii. Grade 3
iv. Lymphovascular invasion present
v. Age 25
c. In patients who have received neo-adjuvant
chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant
and/or adjuvant chemotherapy or RT are eligible.
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy
COLORECTAL COHORT INCLUSION CRITERIA
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone
resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally ≤1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins
GASTRO-OESOPHAGEAL
COHORT INCLUSION CRITERIA
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the
oesophagus, gastro-oesophageal
junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent
PROSTATE COHORT INCLUSION CRITERIA
1. Men with histologically confirmed node negative non-metastatic adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
a. Radical prostatectomy
b. Radical RT
c. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
(a) Prostatectomy patients
4. Open, laparoscopic or robotic radical prostatectomy
5. Men treated with immediate adjuvant RT
6. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
7. Men randomised to any of the 3 arms of RADICALS HD are eligible
(b) Radical RT patients
9. Men receiving neo-adjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3yrs
(c) Salvage RT patients following PSA rise after previous radical prostatectomy
13. Men treated with salvage RT following a rise in PSA are eligible
14. Men receiving neo-and/ or adjuvant hormone therapy planned for a maximum of 3yrs
15. Men randomised to any of the 3 arms of RADICALS HD are eligible

Exclusion criteria:
COMMON EXCLUSION CRITERIA
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or
sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
3. Current use of anti-coagulants.
4. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term
therapy.
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of
bleeding has been surgically removed.
7. Active or previous history of inflammatory bowel disease.
8. History of moderate or severe renal impairment, with eGFR3 years.
3. Bilateral orchidectomy.

Principal Investigator for this trial: Dr Georgina Walker

Research Ethics Committee Reference: 14/SC/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase III doubleblind placebocontrolled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumours.

Summary:
Add-Aspirin is a large clinical trial for people who have had treatment for breast, colorectal, gastro-oesophageal
or prostate cancer. The aim of the trial is to find out whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back.
Participants will self-administer 100mg aspirin once daily for 8 weeks. After 8 weeks, if taking regular aspirin does not cause any serious problems, participants will be randomly allocated to self-administer either a 300mg aspirin tablet, a 100mg aspirin tablet or a placebo tablet once daily for at least five years. Participants who are 75 years old or over, will only be allocated to 100mg aspirin tablets daily or placebo tablets. To ensure the results of the trial are as reliable as possible, neither the participants, nor the clinicians will know which tablets participants are allocated to.
In total, 9,920 participants will be randomised into the trial over 3 – 6 years (depending on tumour site). All participants will be followed-up within the trial for at least 5 years. In the UK, long-term follow-up data will also be obtained from routinely-collected healthcare databases.
A programme of associated correlative science is planned incorporating both short and long-term projects which will
investigate key questions including: determining the mechanism of action for an anti-cancer effect of aspirin;
determining biomarkers that identify participants most likely to experience serious aspirin-related toxicity; determining the roles of genotypic and phenotypic differences in aspirin’s actions; identifying individuals who will benefit most or least from aspirin and determining the mechanisms underlying potential non-cancer benefits of aspirin.

Inclusion criteria:
COMMON INCLUSION CRITERIA
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease
BREAST COHORT INCLUSION CRITERIA
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
a. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further
intervention) should be completed prior to registration
b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT)
a. Patients who have undergone breastconserving
surgery should receive adjuvant RT
b. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
c. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not)
receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
a. Node positive
b. Node negative with high-risk features -2 or more of:
i. ER negative
ii. HER2 positive
iii. Grade 3
iv. Lymphovascular invasion present
v. Age 25
c. In patients who have received neo-adjuvant
chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant
and/or adjuvant chemotherapy or RT are eligible.
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy
COLORECTAL COHORT INCLUSION CRITERIA
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone
resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally ≤1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins
GASTRO-OESOPHAGEAL
COHORT INCLUSION CRITERIA
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the
oesophagus, gastro-oesophageal
junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent
PROSTATE COHORT INCLUSION CRITERIA
1. Men with histologically confirmed node negative non-metastatic adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
a. Radical prostatectomy
b. Radical RT
c. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
(a) Prostatectomy patients
4. Open, laparoscopic or robotic radical prostatectomy
5. Men treated with immediate adjuvant RT
6. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
7. Men randomised to any of the 3 arms of RADICALS HD are eligible
(b) Radical RT patients
9. Men receiving neo-adjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3yrs
(c) Salvage RT patients following PSA rise after previous radical prostatectomy
13. Men treated with salvage RT following a rise in PSA are eligible
14. Men receiving neo-and/ or adjuvant hormone therapy planned for a maximum of 3yrs
15. Men randomised to any of the 3 arms of RADICALS HD are eligible

Exclusion criteria:
COMMON EXCLUSION CRITERIA
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or
sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
3. Current use of anti-coagulants.
4. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term
therapy.
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of
bleeding has been surgically removed.
7. Active or previous history of inflammatory bowel disease.
8. History of moderate or severe renal impairment, with eGFR3 years.
3. Bilateral orchidectomy.

Principal Investigator for this trial: Dr Georgina Walker

Research Ethics Committee Reference: 14/SC/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase III doubleblind placebocontrolled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumours.

Summary:
Add-Aspirin is a large clinical trial for people who have had treatment for breast, colorectal, gastro-oesophageal
or prostate cancer. The aim of the trial is to find out whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back.
Participants will self-administer 100mg aspirin once daily for 8 weeks. After 8 weeks, if taking regular aspirin does not cause any serious problems, participants will be randomly allocated to self-administer either a 300mg aspirin tablet, a 100mg aspirin tablet or a placebo tablet once daily for at least five years. Participants who are 75 years old or over, will only be allocated to 100mg aspirin tablets daily or placebo tablets. To ensure the results of the trial are as reliable as possible, neither the participants, nor the clinicians will know which tablets participants are allocated to.
In total, 9,920 participants will be randomised into the trial over 3 – 6 years (depending on tumour site). All participants will be followed-up within the trial for at least 5 years. In the UK, long-term follow-up data will also be obtained from routinely-collected healthcare databases.
A programme of associated correlative science is planned incorporating both short and long-term projects which will
investigate key questions including: determining the mechanism of action for an anti-cancer effect of aspirin;
determining biomarkers that identify participants most likely to experience serious aspirin-related toxicity; determining the roles of genotypic and phenotypic differences in aspirin’s actions; identifying individuals who will benefit most or least from aspirin and determining the mechanisms underlying potential non-cancer benefits of aspirin.

Inclusion criteria:
COMMON INCLUSION CRITERIA
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease
BREAST COHORT INCLUSION CRITERIA
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
a. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further
intervention) should be completed prior to registration
b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT)
a. Patients who have undergone breastconserving
surgery should receive adjuvant RT
b. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
c. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not)
receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
a. Node positive
b. Node negative with high-risk features -2 or more of:
i. ER negative
ii. HER2 positive
iii. Grade 3
iv. Lymphovascular invasion present
v. Age 25
c. In patients who have received neo-adjuvant
chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant
and/or adjuvant chemotherapy or RT are eligible.
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy
COLORECTAL COHORT INCLUSION CRITERIA
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone
resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally ≤1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins
GASTRO-OESOPHAGEAL
COHORT INCLUSION CRITERIA
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the
oesophagus, gastro-oesophageal
junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent
PROSTATE COHORT INCLUSION CRITERIA
1. Men with histologically confirmed node negative non-metastatic adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
a. Radical prostatectomy
b. Radical RT
c. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
(a) Prostatectomy patients
4. Open, laparoscopic or robotic radical prostatectomy
5. Men treated with immediate adjuvant RT
6. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
7. Men randomised to any of the 3 arms of RADICALS HD are eligible
(b) Radical RT patients
9. Men receiving neo-adjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3yrs
(c) Salvage RT patients following PSA rise after previous radical prostatectomy
13. Men treated with salvage RT following a rise in PSA are eligible
14. Men receiving neo-and/ or adjuvant hormone therapy planned for a maximum of 3yrs
15. Men randomised to any of the 3 arms of RADICALS HD are eligible

Exclusion criteria:
COMMON EXCLUSION CRITERIA
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or
sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
3. Current use of anti-coagulants.
4. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term
therapy.
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of
bleeding has been surgically removed.
7. Active or previous history of inflammatory bowel disease.
8. History of moderate or severe renal impairment, with eGFR3 years.
3. Bilateral orchidectomy.

Principal Investigator for this trial: Dr Vanessa Potter

Research Ethics Committee Reference:

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase II randomized, double blind, placebo controlled trial of radium-223 dichloride in combination with exemestane and everolimus versus placebo in combination with exemestane and everolimus when administered to metastatic HER2 negative hormone receptor positive breast cancer subjects with bone metastases.

Summary:
Patients with metastatic breast cancer with bone involvement whose breast cancer is HER2 negative and ER positive are treated with exemestane and everolimus. These patients will be invited to participate on this study. The purpose of this study is to understand if adding radium-223 dichloride to exemestane and everolimus helps patients to delay the occurrence of symptomatic skeletal events. Patients will be randomly given one of the following treatments: radium 223
dichloride 50 kBq/kg or placebo (normal saline), in addition to exemestane and everolimus. The study will be double blind, which means neither the patient nor their doctor will know which treatment option the patient is on. The main
objective of this study is to assess efficacy and safety of radium223 dichloride in combination with exemestane and everolimus in subjects with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor positive breast cancer with bone metastases.

About 310 patients, from approximately 25 countries are anticipated to participate in this study.

Inclusion criteria:
• Have provided written informed consent. Subjects must be able to understand and be willing to sign the written
informed consent. A signed ICF must be appropriately obtained prior to the conduct of any trial-specific
procedure.
• Documentation of histological or cytological confirmation of ER+ and HER2 negative adenocarcinoma of the breast must be available. HER2 status should be determined by an accredited/Ministry of Health approved laboratory by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH).
• Tumors (from either primary or metastatic sites) must be ER+ defined as ≥10% positive tumor nuclei in the analyzed sample. ER+/progesterone receptor positive (PR+) and ER+/progesterone receptor negative (PR-)
subjects are eligible whereas estrogen receptor negative (ER)/ PR+ and ER/PR-disease will not be eligible.
• Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or
radiotherapy. Women of reproductive potential and their male partners must agree to use adequate contraception
during treatment and for 6 months following the completion of treatment with radium-223 dichloride.
• Documentation of menopausal status: postmenopausal subjects.
o Postmenopausal
status is defined either by:
o age ≥55 years and one year or more of amenorrhea,
o age Exclusion criteria:
• HER2-positive breast cancer (immunohistochemistry [IHC] =3+, positive FISH, or positive CISH); equivocal or
unknown HER2 status
Note: Subjects with 3+ by IHC cannot be chosen regardless of their FISH/CISH status and those with positive FISH/CISH (≥2 amplifications) cannot be chosen either, regardless of the IHC findings. Subjects with 2+ by IHC will not be eligible if no negative FISH/CISH is available.
•Subjects with any of the following cancers:
o Inflammatory breast cancer
o Bilateral breast cancer or a history of 2 distinct breast cancers.
• History or presence of visceral metastases.
• Subjects who have either received chemotherapy for metastatic disease or are considered by the treating Investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neoadjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
• Subjects with any previous untreated or concurrent cancer that is distinct in primary site or histology from the cancer under study except treated basal cell carcinoma, or superficial bladder tumor (Ta and Tis, American Joint Committee on Cancer, 7th edition). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment, are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of ICF)
• Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system is otherwise not required.
• Imminent or established untreated spinal cord compression based on clinical findings and/or MRI. Following treatment of spinal cord compression, the subject may be eligible if all other eligibility criteria are fulfilled.
• Prior treatment with radium-223 dichloride.
• Prior hemibody external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for Hb, absolute neutrophil count, and platelets.
• Prior systemic radiotherapy with strontium-89,
samarium-153, rhenium-186, or rhenium-188.
• ECOG PS ≥2.
• Blood transfusions or use of erythropoietin within 6 weeks prior to randomization. Platelet transfusions are not allowed within 3 weeks prior to randomization
• Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor or granulocyte colony stimulating factor, within 6 weeks prior to randomization.
• Treatment with an investigational drug or with any anticancer treatments not permitted by the protocol, within 4 weeks prior to randomization
• Chronic conditions associated with non-malignant
abnormal bone growth (e.g., confirmed Paget’s disease of bone)
• Any other serious illness or medical condition such as, but not limited to:
o Any uncontrolled infection
o Cardiac failure New York Heart Association Class III or IV
o Crohn’s disease or ulcerative colitis
o Bone marrow dysplasia
• Previous assignment to treatment in this study

All local label specific criteria for exemestane and everolimus as well as standard-of-care denosumab and bisphosphonates will apply. Subjects must be treated according to the local standardofcare requirements.

Principal Investigator for this trial: Dr Stephen Y Chan

Research Ethics Committee Reference: 14/SW/1085

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase II randomized, double blind, placebo controlled trial of radium-223 dichloride in combination with exemestane and everolimus versus placebo in combination with exemestane and everolimus when administered to metastatic HER2 negative hormone receptor positive breast cancer subjects with bone metastases.

Summary:
Patients with metastatic breast cancer with bone involvement whose breast cancer is HER2 negative and ER positive are treated with exemestane and everolimus. These patients will be invited to participate on this study. The purpose of this study is to understand if adding radium-223 dichloride to exemestane and everolimus helps patients to delay the occurrence of symptomatic skeletal events. Patients will be randomly given one of the following treatments: radium 223
dichloride 50 kBq/kg or placebo (normal saline), in addition to exemestane and everolimus. The study will be double blind, which means neither the patient nor their doctor will know which treatment option the patient is on. The main
objective of this study is to assess efficacy and safety of radium223 dichloride in combination with exemestane and everolimus in subjects with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor positive breast cancer with bone metastases.

About 310 patients, from approximately 25 countries are anticipated to participate in this study.

Inclusion criteria:
• Have provided written informed consent. Subjects must be able to understand and be willing to sign the written
informed consent. A signed ICF must be appropriately obtained prior to the conduct of any trial-specific
procedure.
• Documentation of histological or cytological confirmation of ER+ and HER2 negative adenocarcinoma of the breast must be available. HER2 status should be determined by an accredited/Ministry of Health approved laboratory by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH).
• Tumors (from either primary or metastatic sites) must be ER+ defined as ≥10% positive tumor nuclei in the analyzed sample. ER+/progesterone receptor positive (PR+) and ER+/progesterone receptor negative (PR-)
subjects are eligible whereas estrogen receptor negative (ER)/ PR+ and ER/PR-disease will not be eligible.
• Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or
radiotherapy. Women of reproductive potential and their male partners must agree to use adequate contraception
during treatment and for 6 months following the completion of treatment with radium-223 dichloride.
• Documentation of menopausal status: postmenopausal subjects.
o Postmenopausal
status is defined either by:
o age ≥55 years and one year or more of amenorrhea,
o age Exclusion criteria:
• HER2-positive breast cancer (immunohistochemistry [IHC] =3+, positive FISH, or positive CISH); equivocal or
unknown HER2 status
Note: Subjects with 3+ by IHC cannot be chosen regardless of their FISH/CISH status and those with positive FISH/CISH (≥2 amplifications) cannot be chosen either, regardless of the IHC findings. Subjects with 2+ by IHC will not be eligible if no negative FISH/CISH is available.
•Subjects with any of the following cancers:
o Inflammatory breast cancer
o Bilateral breast cancer or a history of 2 distinct breast cancers.
• History or presence of visceral metastases.
• Subjects who have either received chemotherapy for metastatic disease or are considered by the treating Investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neoadjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
• Subjects with any previous untreated or concurrent cancer that is distinct in primary site or histology from the cancer under study except treated basal cell carcinoma, or superficial bladder tumor (Ta and Tis, American Joint Committee on Cancer, 7th edition). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment, are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of ICF)
• Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system is otherwise not required.
• Imminent or established untreated spinal cord compression based on clinical findings and/or MRI. Following treatment of spinal cord compression, the subject may be eligible if all other eligibility criteria are fulfilled.
• Prior treatment with radium-223 dichloride.
• Prior hemibody external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for Hb, absolute neutrophil count, and platelets.
• Prior systemic radiotherapy with strontium-89,
samarium-153, rhenium-186, or rhenium-188.
• ECOG PS ≥2.
• Blood transfusions or use of erythropoietin within 6 weeks prior to randomization. Platelet transfusions are not allowed within 3 weeks prior to randomization
• Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor or granulocyte colony stimulating factor, within 6 weeks prior to randomization.
• Treatment with an investigational drug or with any anticancer treatments not permitted by the protocol, within 4 weeks prior to randomization
• Chronic conditions associated with non-malignant
abnormal bone growth (e.g., confirmed Paget’s disease of bone)
• Any other serious illness or medical condition such as, but not limited to:
o Any uncontrolled infection
o Cardiac failure New York Heart Association Class III or IV
o Crohn’s disease or ulcerative colitis
o Bone marrow dysplasia
• Previous assignment to treatment in this study

All local label specific criteria for exemestane and everolimus as well as standard-of-care denosumab and bisphosphonates will apply. Subjects must be treated according to the local standardofcare requirements.

Principal Investigator for this trial: Dr Stephen Y Chan

Research Ethics Committee Reference: 14/SW/1085

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase II randomized, double blind, placebo controlled trial of radium-223 dichloride versus placebo when administered to metastatic HER2 negative hormone receptor positive breast cancer subjects with bone metastases treated with hormonal treatment background therapy.

Summary:
Patients with human epidermal growth factor receptor 2 negative, hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy will be invited to participate on this study. The purpose of this study is to understand if adding radium-223 dichloride to hormonal therapy helps patients live longer without symptomatic skeletal complications. Patients will be randomly given one of the following treatments: radium223 dichloride 50 kBq/kg or placebo (normal saline). The study will be double blind, which means neither the patient nor their doctor will know which treatment option the patient is on. The main objective of this study to see if adding radium-223 dichloride to hormonal therapy is effective and safe in patients with epidermal growth factor receptor 2 negative, hormone receptor positive breast cancer with bone metastases.

About 227 patients, from approximately 24 countries are anticipated to participate in this study.

Inclusion criteria:
• Have provided written informed consent. Subjects must be able to understand and be willing to sign the written
informed consent. A signed ICF must be appropriately obtained prior to the conduct of any studyspecific
procedure.
• Documentation of histological or cytological confirmation of ER+ and HER2 negative adenocarcinoma of the breast
must be available. HER2 status should be determined by an accredited/Ministry of Health approved laboratory by
immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH).
• Tumors (from either primary or metastatic sites) must be ER+ defined as ≥10% positive tumor nuclei in the analyzed
sample. ER+/ progesterone positive (PR+), ER+/ progesterone receptor negative (PR-) subjects are eligible whereas estrogen receptor negative (ER)/PR+ and ER/ PR-disease will not be eligible.
• Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or
radiotherapy. Women of reproductive potential and their male partners must agree to use adequate contraception
during treatment and for 6 months following the completion of treatment with radium 223 dichloride/placebo.
• Documentation of menopausal status: postmenopausal or premenopausal subjects are eligible.
o Premenopausal subjects as well as subjects with ovarian radiation or concomitant treatment with an LH-RH
agonist/antagonist must have a negative pregnancy test and agree to use an adequate method of contraception as recommended by their treating physicians.
o Postmenopausal status is defined either by:
o age ≥55 years and one year or more of amenorrhea
o age 30 g/L
• Able to swallow oral medication

Exclusion criteria:
• HER2positive breast cancer (IHC=3+, positive FISH, or positive CISH); equivocal or unknown HER2 status
Note: Subjects with 3+ by IHC cannot be chosen regardless of their FISH/CISH status and those with positive FISH/CISH (≥2 amplifications) cannot be chosen either, regardless of the IHC findings. Subjects with 2+ by IHC will not be eligible if no negative FISH/CISH is available.
• Subjects eligible for treatment with everolimus
• Subjects with any of the following cancers:
o Inflammatory breast cancer
o Bilateral breast cancer or a history of 2 distinct breast cancers
• History and/or presence of visceral metastases
• Subjects who have either received chemotherapy for metastatic disease or are considered by the treating Investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neoadjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
• Subjects with any previous untreated or concurrent cancer that is distinct in primary site or histology from the cancer under study, except treated basal cell carcinoma or superficial bladder tumor (Ta and Tis, American Joint Committee on Cancer, 7th edition). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of informed consent form).
• Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system is otherwise not required.
• Imminent or established untreated spinal cord compression based on clinical findings and/or MRI. Following treatment of spinal cord compression, the subject may be eligible if all other eligibility criteria are fulfilled.
• Prior treatment with radium-223 dichloride
• Prior hemibody external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count, and platelets.
• Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188
• ECOG Performance Status ≥2
• Blood transfusions or use of erythropoietin within 6 weeks prior to randomization. Platelet transfusions are not
allowed within 3 weeks prior to randomization.
• Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor or granulocyte colony-stimulating factor, within 6 weeks prior to randomization.
• Treatment with an investigational drug or with any anti cancer treatments not permitted by the protocol, within 4 weeks prior to randomization
• Chronic conditions associated with nonmalignant
abnormal bone growth (e.g., confirmed Paget’s disease of bone)
• Any other serious illness or medical condition such as, but not limited to:
o Any uncontrolled infection
o Cardiac failure New York Heart Association Class III or IV
o Crohn’s disease or ulcerative colitis
o Bone marrow dysplasia
• Previous assignment to treatment in this study
All local label specific criteria for the standard of care hormonal treatment as well as denosumab and
bisphosphonates apply. Subjects must be treated according to the local standard of care requirements.

Principal Investigator for this trial: Dr Stephen Y Chan

Research Ethics Committee Reference: 14/YH/1141

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase II randomized, double blind, placebo controlled trial of radium-223 dichloride versus placebo when administered to metastatic HER2 negative hormone receptor positive breast cancer subjects with bone metastases treated with hormonal treatment background therapy.

Summary:
Patients with human epidermal growth factor receptor 2 negative, hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy will be invited to participate on this study. The purpose of this study is to understand if adding radium-223 dichloride to hormonal therapy helps patients live longer without symptomatic skeletal complications. Patients will be randomly given one of the following treatments: radium223 dichloride 50 kBq/kg or placebo (normal saline). The study will be double blind, which means neither the patient nor their doctor will know which treatment option the patient is on. The main objective of this study to see if adding radium-223 dichloride to hormonal therapy is effective and safe in patients with epidermal growth factor receptor 2 negative, hormone receptor positive breast cancer with bone metastases.

About 227 patients, from approximately 24 countries are anticipated to participate in this study.

Inclusion criteria:
• Have provided written informed consent. Subjects must be able to understand and be willing to sign the written
informed consent. A signed ICF must be appropriately obtained prior to the conduct of any studyspecific
procedure.
• Documentation of histological or cytological confirmation of ER+ and HER2 negative adenocarcinoma of the breast
must be available. HER2 status should be determined by an accredited/Ministry of Health approved laboratory by
immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH).
• Tumors (from either primary or metastatic sites) must be ER+ defined as ≥10% positive tumor nuclei in the analyzed
sample. ER+/ progesterone positive (PR+), ER+/ progesterone receptor negative (PR-) subjects are eligible whereas estrogen receptor negative (ER)/PR+ and ER/ PR-disease will not be eligible.
• Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or
radiotherapy. Women of reproductive potential and their male partners must agree to use adequate contraception
during treatment and for 6 months following the completion of treatment with radium 223 dichloride/placebo.
• Documentation of menopausal status: postmenopausal or premenopausal subjects are eligible.
o Premenopausal subjects as well as subjects with ovarian radiation or concomitant treatment with an LH-RH
agonist/antagonist must have a negative pregnancy test and agree to use an adequate method of contraception as recommended by their treating physicians.
o Postmenopausal status is defined either by:
o age ≥55 years and one year or more of amenorrhea
o age 30 g/L
• Able to swallow oral medication

Exclusion criteria:
• HER2positive breast cancer (IHC=3+, positive FISH, or positive CISH); equivocal or unknown HER2 status
Note: Subjects with 3+ by IHC cannot be chosen regardless of their FISH/CISH status and those with positive FISH/CISH (≥2 amplifications) cannot be chosen either, regardless of the IHC findings. Subjects with 2+ by IHC will not be eligible if no negative FISH/CISH is available.
• Subjects eligible for treatment with everolimus
• Subjects with any of the following cancers:
o Inflammatory breast cancer
o Bilateral breast cancer or a history of 2 distinct breast cancers
• History and/or presence of visceral metastases
• Subjects who have either received chemotherapy for metastatic disease or are considered by the treating Investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neoadjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
• Subjects with any previous untreated or concurrent cancer that is distinct in primary site or histology from the cancer under study, except treated basal cell carcinoma or superficial bladder tumor (Ta and Tis, American Joint Committee on Cancer, 7th edition). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of informed consent form).
• Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system is otherwise not required.
• Imminent or established untreated spinal cord compression based on clinical findings and/or MRI. Following treatment of spinal cord compression, the subject may be eligible if all other eligibility criteria are fulfilled.
• Prior treatment with radium-223 dichloride
• Prior hemibody external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count, and platelets.
• Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188
• ECOG Performance Status ≥2
• Blood transfusions or use of erythropoietin within 6 weeks prior to randomization. Platelet transfusions are not
allowed within 3 weeks prior to randomization.
• Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor or granulocyte colony-stimulating factor, within 6 weeks prior to randomization.
• Treatment with an investigational drug or with any anti cancer treatments not permitted by the protocol, within 4 weeks prior to randomization
• Chronic conditions associated with nonmalignant
abnormal bone growth (e.g., confirmed Paget’s disease of bone)
• Any other serious illness or medical condition such as, but not limited to:
o Any uncontrolled infection
o Cardiac failure New York Heart Association Class III or IV
o Crohn’s disease or ulcerative colitis
o Bone marrow dysplasia
• Previous assignment to treatment in this study
All local label specific criteria for the standard of care hormonal treatment as well as denosumab and
bisphosphonates apply. Subjects must be treated according to the local standard of care requirements.

Principal Investigator for this trial: Dr Stephen Y Chan

Research Ethics Committee Reference: 14/YH/1141

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Establishing a Biobank and Database as a National Resource for Characterising Indolent and Aggressive forms of Mantle Cell Lymphoma, an Observational Study.

Summary:
Mantle Cell Lymphoma (MCL) is a type of nonHodgkin’s lymphoma a cancer of the lymphocytes (white blood cells) that occurs when the growth of these cells is out of control. MCL is a relatively rare, usually aggressive cancer for which there is currently no known cure. Many patients are treated as soon as they are diagnosed because they generally have a poor prognosis. However, our experience tells us that there is a subset of patients that have a less aggressive form of the disease. They can remain asymptomatic, sometimes for years. These patients need not be treated with systemic chemotherapy straight away and `watching and waiting’ does not affect the outcome at all. There are currently no tests that can tell us which patients have indolent behaving disease at diagnosis. Knowing this will be really helpful in finding the best way to treat people with this disease in the future. The only way that we can really be sure which type of MCL a patient has, is to observe what happens to them over the next few years. We will collect baseline blood and saliva samples, diagnostic biopsy material and clinical information from patients who are newly diagnosed with MCL. These samples will be stored in a Biobank. After this, patients will not directly be involved as the information we need to collect can be found in the medical notes. We aim to recruit 300 participants over 3 years. Once the study is completed, we will know which patients have indolent MCL and which patients have aggressive MCL. We will then study the stored samples to try to identify and understand the differences between indolent and aggressive forms of MCL.

Inclusion criteria:
aged 16 and over newly diagnosed mantle cell lymphoma able to give consent

Exclusion criteria:
Received systemic treatment for mantle cell lymphoma (localised radiotherapy is acceptable)

Principal Investigator for this trial: Dr Christopher P Fox

Research Ethics Committee Reference: 14/WA/1192

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Establishing a Biobank and Database as a National Resource for Characterising Indolent and Aggressive forms of Mantle Cell Lymphoma, an Observational Study.

Summary:
Mantle Cell Lymphoma (MCL) is a type of nonHodgkin’s lymphoma a cancer of the lymphocytes (white blood cells) that occurs when the growth of these cells is out of control. MCL is a relatively rare, usually aggressive cancer for which there is currently no known cure. Many patients are treated as soon as they are diagnosed because they generally have a poor prognosis. However, our experience tells us that there is a subset of patients that have a less aggressive form of the disease. They can remain asymptomatic, sometimes for years. These patients need not be treated with systemic chemotherapy straight away and `watching and waiting’ does not affect the outcome at all. There are currently no tests that can tell us which patients have indolent behaving disease at diagnosis. Knowing this will be really helpful in finding the best way to treat people with this disease in the future. The only way that we can really be sure which type of MCL a patient has, is to observe what happens to them over the next few years. We will collect baseline blood and saliva samples, diagnostic biopsy material and clinical information from patients who are newly diagnosed with MCL. These samples will be stored in a Biobank. After this, patients will not directly be involved as the information we need to collect can be found in the medical notes. We aim to recruit 300 participants over 3 years. Once the study is completed, we will know which patients have indolent MCL and which patients have aggressive MCL. We will then study the stored samples to try to identify and understand the differences between indolent and aggressive forms of MCL.

Inclusion criteria:
aged 16 and over newly diagnosed mantle cell lymphoma able to give consent

Exclusion criteria:
Received systemic treatment for mantle cell lymphoma (localised radiotherapy is acceptable)

Principal Investigator for this trial: Dr Mark Bishton

Research Ethics Committee Reference: 14/WA/1192

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Genetic basis of cranial malformations

Summary:
Children born with malformations of the face and skull often require craniofacial surgery. There malformations are diverse the most common is craniosynostosis, which describes the premature fusion of the fibrous joints between the skull bones. Owing to the demanding, mutidisciplinary nature of this surgery, expertise is concentrated at four specialist units in England (located at Birmingham, Liverpool, London and Oxford(, funded by the NHS National Commissioning Group. Many craniofacial malformations are caused by alterations in the genetic blueprint, some of which have been identified over the past 15 years by work at Oxford, Great Ormond Street and elsewhere. however more research is required to identify further faulty genes in craniofacial malformations, and to find the natural genetic variations (polymorphisms) that predispose to these malformations. For these purposes, a larger sample size is required. The aim of this proposal is to enable sample collection for genetic research for all patients attending the four specialised craniofacial units. Samples (usually blood, but sometimes mouthbrushings, saliva, skin or bone) would be obtained from the affected individual (usually a child) at the time of surgery or, in the case of blood, as part of a routine phebotomy procedure. Blood samples would also be obtained from the parents.
The pursose of identifying new genes in craniofacial malformation is twofold. First, if a faulty gene is found, this information enables a precise diagnosis to be made, permitting accurate genetic counselling about the risks of recurrence in the family, and allows new genetic tests to be offered. Sometimes the information may have implications for the longer term outlook (prognosis) and in the future, might impact on treatment. Second, the identification of statistical associations of common genetic variation with craniofacial malformations, even if of no direct medical value, gives information on how these complex conditions arise. For example, it may help to identify environment facts that could potentially be modified.

Inclusion criteria:
1. All patients attending one of the four nationally funded craniofacial unites in England (Birmingham Children’s Hospital, Alder Hey Hospital Liverpool, Great Ormond Street Hospital London and John Radcliffe Hospital Oxford), who (a) on clinical assessment are found to have a significant craniofacial disorder expected to require surgery, or (b) in who clinical assessment of the phenotype and/or family history suggests that the subject may be particularly instructive for further genetic research or that this may be beneficial for their diagnosis
2. Patients not attending one of the above four craniofacial units but referred to the study by a Consultant Clinical Geneticist, Paediatrician, or Surgeon for genetic assessment of a craniofacial disorger

Exclusion criteria:
1. Mild disorders not like to require surgery
2. Refusal of consent
3. Referral from a source other than those stipulated
4. Individuals with craniofacial disorders who have already had a surgical procedure and do not require a further procedure will normally be excluded, with the 1 (b) and 2
5. Isolated clefts of the lip and/pr palate
6. Mentally incompetent adults

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 09/H0706/20

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Genetic basis of cranial malformations

Summary:
Children born with malformations of the face and skull often require craniofacial surgery. There malformations are diverse the most common is craniosynostosis, which describes the premature fusion of the fibrous joints between the skull bones. Owing to the demanding, mutidisciplinary nature of this surgery, expertise is concentrated at four specialist units in England (located at Birmingham, Liverpool, London and Oxford(, funded by the NHS National Commissioning Group. Many craniofacial malformations are caused by alterations in the genetic blueprint, some of which have been identified over the past 15 years by work at Oxford, Great Ormond Street and elsewhere. however more research is required to identify further faulty genes in craniofacial malformations, and to find the natural genetic variations (polymorphisms) that predispose to these malformations. For these purposes, a larger sample size is required. The aim of this proposal is to enable sample collection for genetic research for all patients attending the four specialised craniofacial units. Samples (usually blood, but sometimes mouthbrushings, saliva, skin or bone) would be obtained from the affected individual (usually a child) at the time of surgery or, in the case of blood, as part of a routine phebotomy procedure. Blood samples would also be obtained from the parents.
The pursose of identifying new genes in craniofacial malformation is twofold. First, if a faulty gene is found, this information enables a precise diagnosis to be made, permitting accurate genetic counselling about the risks of recurrence in the family, and allows new genetic tests to be offered. Sometimes the information may have implications for the longer term outlook (prognosis) and in the future, might impact on treatment. Second, the identification of statistical associations of common genetic variation with craniofacial malformations, even if of no direct medical value, gives information on how these complex conditions arise. For example, it may help to identify environment facts that could potentially be modified.

Inclusion criteria:
1. All patients attending one of the four nationally funded craniofacial unites in England (Birmingham Children’s Hospital, Alder Hey Hospital Liverpool, Great Ormond Street Hospital London and John Radcliffe Hospital Oxford), who (a) on clinical assessment are found to have a significant craniofacial disorder expected to require surgery, or (b) in who clinical assessment of the phenotype and/or family history suggests that the subject may be particularly instructive for further genetic research or that this may be beneficial for their diagnosis
2. Patients not attending one of the above four craniofacial units but referred to the study by a Consultant Clinical Geneticist, Paediatrician, or Surgeon for genetic assessment of a craniofacial disorger

Exclusion criteria:
1. Mild disorders not like to require surgery
2. Refusal of consent
3. Referral from a source other than those stipulated
4. Individuals with craniofacial disorders who have already had a surgical procedure and do not require a further procedure will normally be excluded, with the 1 (b) and 2
5. Isolated clefts of the lip and/pr palate
6. Mentally incompetent adults

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 09/H0706/20

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

GENPROS Analysing outcomes after prostate cancer diagnosis and treatment in carriers of rare germline mutations in cancer predisposition genes

Summary:
GENPROS aims to analyse the outcomes of patients with rare gene mutations in the cancer predisposition genes, BRCA1, BRCA2, HOXB13, and Lynch Syndrome, after a diagnosis of and treatment for prostate cancer (PCa). The study includes a cohort of gene mutation carriers with PCa matched with a control group of men with PCa who are known not to carry a mutation in the same gene. Clinical data regarding treatment and patient outcome will be collected retrospectively and prospectively. Archived tumour samples will also be collected for tumour profiling. A blood or saliva sample will be taken, if the participant consents to this part of the study, for genetic profiling to investigate any association of other inherited factors with PCa outcomes. Information obtained from this study will be of critical importance to support clinical trials investigating the most appropriate management of PCa in this group of patients at increased risk of prostate cancer.

Inclusion criteria:
Men diagnosed with PCa are eligible for the study if they are either: · known carriers of a germline mutation in a gene associated with PCa risk (e.g. BRCA1, BRCA2, HOXB13 and Lynch Syndrome genes) · known not to carry a mutation in one of the genes above

Exclusion criteria:
· patients under 18 years of age · patients who are unable to give informed consent · patients who cannot be traced (Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 14/LO/0072

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

GENPROS Analysing outcomes after prostate cancer diagnosis and treatment in carriers of rare germline mutations in cancer predisposition genes

Summary:
GENPROS aims to analyse the outcomes of patients with rare gene mutations in the cancer predisposition genes, BRCA1, BRCA2, HOXB13, and Lynch Syndrome, after a diagnosis of and treatment for prostate cancer (PCa). The study includes a cohort of gene mutation carriers with PCa matched with a control group of men with PCa who are known not to carry a mutation in the same gene. Clinical data regarding treatment and patient outcome will be collected retrospectively and prospectively. Archived tumour samples will also be collected for tumour profiling. A blood or saliva sample will be taken, if the participant consents to this part of the study, for genetic profiling to investigate any association of other inherited factors with PCa outcomes. Information obtained from this study will be of critical importance to support clinical trials investigating the most appropriate management of PCa in this group of patients at increased risk of prostate cancer.

Inclusion criteria:
Men diagnosed with PCa are eligible for the study if they are either: · known carriers of a germline mutation in a gene associated with PCa risk (e.g. BRCA1, BRCA2, HOXB13 and Lynch Syndrome genes) · known not to carry a mutation in one of the genes above

Exclusion criteria:
· patients under 18 years of age · patients who are unable to give informed consent · patients who cannot be traced (Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 14/LO/0072

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

British Childhood Cancer Survivor Study (BCCSS) Case-control studies into risks of adverse-health outcomes in survivors of childhood cancer

Summary:
The proposed case-control studies are an extension of the British Childhood Cancer Survivor Study (BCCSS) cohort.
The BCCSS is a long-term follow-up (i.e. cohort) study of adult survivors of childhood cancer. The proposed nested
case-control studies will focus on the risks of adverse health outcomes, including, but not limited to, cardiac disease,
cerebrovascular disease, and subsequent primary neoplasms after childhood cancer and quantify the extent to which
these risks are related to previous radiotherapy and chemotherapy given to treat childhood cancer. Adult survivors of
childhood cancer will be approached to obtain written consent to access their medical records, and with this consent
hospitals will be contacted to obtain copies of relevant medical records. For a limited sub-set a request for a saliva
sample will be made to obtain DNA.

Inclusion criteria:
Inclusion criteria for `cases’
Cases are those survivors in the underlying cohort who have been diagnosed with an adverse health outcome such
as a subsequent primary neoplasm, cardiac disease or cerebrovascular disease or known to have died of such a
condition.
Previously diagnosed with cancer aged 0-15 years, between 1940 and 2006, in Britain
Survived at least 5-years from original cancer diagnosis
Currently over age 16 years
Inclusion criteria for `controls’
Controls will be randomly selected from among those survivors who have not been diagnosed with the adverse
health outcome of interest. Only survivors who previously completed a British Childhood Cancer Survivor Study
questionnaire and who gave permission for the Study Centre to keep their confidential information will be contacted.
We will not contact survivors who did not complete a British Childhood Cancer Survivor Study questionnaire or those
survivors who did complete a questionnaire and indicated that they did not wish to be contacted in the future.
Previously diagnosed with cancer aged 0-15 years, between 1940 and 2006, in Britain
Survived at least 5-years from original cancer diagnosis
Currently over age 16 years

Exclusion criteria:
Exclusion criteria
Patients lacking capacity to consent for themselves

Principal Investigator for this trial: Professor Richard Grundy

Research Ethics Committee Reference: 14/LO/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

British Childhood Cancer Survivor Study (BCCSS) Case-control studies into risks of adverse-health outcomes in survivors of childhood cancer

Summary:
The proposed casecontrol studies are an extension of the British Childhood Cancer Survivor Study (BCCSS) cohort. The BCCSS is a longterm followup (i.e. cohort) study of adult survivors of childhood cancer. The proposed nested casecontrol studies will focus on the risks of adverse health outcomes, including, but not limited to, cardiac disease, cerebrovascular disease, and subsequent primary neoplasms after childhood cancer and quantify the extent to which these risks are related to previous radiotherapy and chemotherapy given to treat childhood cancer. Adult survivors of childhood cancer will be approached to obtain written consent to access their medical records, and with this consent hospitals will be contacted to obtain copies of relevant medical records. For a limited subset a request for a saliva sample will be made to obtain DNA.

Inclusion criteria:
Inclusion criteria for `cases’ Cases are those survivors in the underlying cohort who have been diagnosed with an adverse health outcome such as a subsequent primary neoplasm, cardiac disease or cerebrovascular disease or known to have died of such a condition. Previously diagnosed with cancer aged 015 years, between 1940 and 2006, in Britain Survived at least 5years from original cancer diagnosis Currently over age 16 years Inclusion criteria for `controls’ Controls will be randomly selected from among those survivors who have not been diagnosed with the adverse health outcome of interest. Only survivors who previously completed a British Childhood Cancer Survivor Study questionnaire and who gave permission for the Study Centre to keep their confidential information will be contacted. We will not contact survivors who did not complete a British Childhood Cancer Survivor Study questionnaire or those survivors who did complete a questionnaire and indicated that they did not wish to be contacted in the future. Previously diagnosed with cancer aged 015 years, between 1940 and 2006, in Britain Survived at least 5years from original cancer diagnosis Currently over age 16 years

Exclusion criteria:
Exclusion criteria Patients lacking capacity to consent for themselves

Principal Investigator for this trial: Professor Richard Grundy

Research Ethics Committee Reference: 14/LO/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Study of Adults and Adolescents with Russell Silver syndrome in the UK

Summary:
Russell Silver syndrome is a rare, genetic disorder of growth, which starts in the womb and significantly restricts final
height (to 140-151 cm). It is usually due to a genetic fault on chromosome 11. Currently children are offered growth
hormone (GH), which improves adult height by 4 cm in babies born small. Patients are not necessarily GH deficient
and families do not know if there are potential risks with treatment therefore the decision is extremely difficult. GH
treatment involves daily injections and costs approximately £50 000 per patient. Knowing the benefits of this treatment
would also allow for the best allocation of NHS resources for public benefit.
This study aims to recruit 100 patients across the UK, with a genetic diagnosis of RSS aged 13 years and above.
Height, weight, blood pressure and heart disease risk factors will be compared to look for differences between those
treated with GH and those who were not. Participants will be seen at a centre as close as possible to their home.
Visits will last approximately three hours and involve clinical examination, assessment of quality of life, a cheek swab,
and a blood test after fasting for six hours. Adult patients will have the option of providing a hair sample and/or
undergoing a skin biopsy. Participants will be asked whether they would be willing to participate in an indepth
interview about their life experiences. 30-34 participants would then be selected and interviewed at a later date in a
location convenient to the participant.
The research study is funded by the National Institute for Health Research for three years and aims to answer the
question of whether GH is beneficial in RSS so that families and doctors have more guidance.

Inclusion criteria:
The eligible participants will be people diagnosed with Russell-Silver syndrome (RSS). The lower age limit is 13 in
order to increase the number of potential participants. If a potential recruit has not had a genetic diagnosis, we will
help to arrange testing by the GP or hospital clinician before inclusion in the study. Qualified clinical genetics
members of the research team can discuss the diagnosis with the GP and testing can be offered by the Wessex
Regional Genetics Service from saliva samples sent by post.

Exclusion criteria:
Excluding people who do not have a genetically proven cause of RSS will make the study group more uniform. This
will make the results more reliable.

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 13/SC/0630

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Study of Adults and Adolescents with Russell Silver syndrome in the UK

Summary:
Russell Silver syndrome is a rare, genetic disorder of growth, which starts in the womb and significantly restricts final height (to 140151 cm). It is usually due to a genetic fault on chromosome 11. Currently children are offered growth hormone (GH), which improves adult height by 4 cm in babies born small. Patients are not necessarily GH deficient and families do not know if there are potential risks with treatment therefore the decision is extremely difficult. GH treatment involves daily injections and costs approximately £50 000 per patient. Knowing the benefits of this treatment would also allow for the best allocation of NHS resources for public benefit. This study aims to recruit 100 patients across the UK, with a genetic diagnosis of RSS aged 13 years and above. Height, weight, blood pressure and heart disease risk factors will be compared to look for differences between those treated with GH and those who were not. Participants will be seen at a centre as close as possible to their home. Visits will last approximately three hours and involve clinical examination, assessment of quality of life, a cheek swab, and a blood test after fasting for six hours. Adult patients will have the option of providing a hair sample and/or undergoing a skin biopsy. Participants will be asked whether they would be willing to participate in an indepth interview about their life experiences. 3034 participants would then be selected and interviewed at a later date in a location convenient to the participant. The research study is funded by the National Institute for Health Research for three years and aims to answer the question of whether GH is beneficial in RSS so that families and doctors have more guidance.

Inclusion criteria:
The eligible participants will be people diagnosed with RussellSilver syndrome (RSS). The lower age limit is 13 in order to increase the number of potential participants. If a potential recruit has not had a genetic diagnosis, we will help to arrange testing by the GP or hospital clinician before inclusion in the study. Qualified clinical genetics members of the research team can discuss the diagnosis with the GP and testing can be offered by the Wessex Regional Genetics Service from saliva samples sent by post.

Exclusion criteria:
Excluding people who do not have a genetically proven cause of RSS will make the study group more uniform. This will make the results more reliable.

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 13/SC/0630

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Exploring the biological processes underlying mutational signatures identified in patients with inherited disorders and in patients exposed to mutagens

Summary:
Recently, my colleagues and I searched for every mutation in the DNA of breast cancers from 21 women. Using computerbased tools we showed that many patterns exist in breast cancers which were not appreciated before. However, our knowledge and understanding of these mutation patterns is limited. In this project, we aim to understand how and why mutation patterns are generated and whether these patterns occur because of internal or externally arising DNA damage or because the essential DNA repair toolkit in the cell is awry. Because some people are born with naturally occurring defects in genes involved in repair of DNA, these patients provide a rare insight into the mutation patterns that can arise in human beings. Patients with inherited DNA repair/replication disorders and patients with a history of strong exposure to DNA damaging agents will be recruited and consented into this study by staff at clinical genetics services in the UK and around the world. Linked anonymised blood and saliva samples and skin biopsies will be taken from these patients and sent to the Wellcome Trust Sanger Institute for whole genome sequencing to explore the biological basis of DNA damage and repair signatures. A resource of linked anonymised induced pluripotent stem cells (iPSCs) and/or lymphoblastoid cell lines (LCLs) from the patients will be established to study mutational patterns under different experimental conditions. Ultimately, but outside the scope of this current study, data will be compared to mutational signatures extracted from largescale sequencing of cancer genomes, giving us insight into the perturbations that happen during cancer development.

Inclusion criteria:
Consented. Suffering from an inherited DNA repair/replication disorder as identified by the Clinical Genetics Service or history of strong exposure to a potential DNA damaging compound. Less than 80 years of age. A set of healthy agematched individuals will also be required to serve as controls.

Exclusion criteria:
Not consented. Not suffering from an inherited disorder or other strong chemical exposure that could produce mutational patterns in the DNA of cells. Over 80 years old.

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 13/EE/0302

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Exploring the biological processes underlying mutational signatures identified in patients with inherited disorders and in patients exposed to mutagens

Summary:
Recently, my colleagues and I searched for every mutation in the DNA of breast cancers from 21 women. Using computerbased tools we showed that many patterns exist in breast cancers which were not appreciated before. However, our knowledge and understanding of these mutation patterns is limited. In this project, we aim to understand how and why mutation patterns are generated and whether these patterns occur because of internal or externally arising DNA damage or because the essential DNA repair toolkit in the cell is awry. Because some people are born with naturally occurring defects in genes involved in repair of DNA, these patients provide a rare insight into the mutation patterns that can arise in human beings. Patients with inherited DNA repair/replication disorders and patients with a history of strong exposure to DNA damaging agents will be recruited and consented into this study by staff at clinical genetics services in the UK and around the world. Linked anonymised blood and saliva samples and skin biopsies will be taken from these patients and sent to the Wellcome Trust Sanger Institute for whole genome sequencing to explore the biological basis of DNA damage and repair signatures. A resource of linked anonymised induced pluripotent stem cells (iPSCs) and/or lymphoblastoid cell lines (LCLs) from the patients will be established to study mutational patterns under different experimental conditions. Ultimately, but outside the scope of this current study, data will be compared to mutational signatures extracted from largescale sequencing of cancer genomes, giving us insight into the perturbations that happen during cancer development.

Inclusion criteria:
Consented. Suffering from an inherited DNA repair/replication disorder as identified by the Clinical Genetics Service or history of strong exposure to a potential DNA damaging compound. Less than 80 years of age. A set of healthy agematched individuals will also be required to serve as controls.

Exclusion criteria:
Not consented. Not suffering from an inherited disorder or other strong chemical exposure that could produce mutational patterns in the DNA of cells. Over 80 years old.

Principal Investigator for this trial: Dr Rachel Harrison

Research Ethics Committee Reference: 13/EE/0302

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

LEUCOPATCHTM IN THE MANAGEMENT OF HARD-TO-HEAL DIABETIC FOOT ULCERS

Summary:
Diabetic foot ulcers are the source of considerable suffering and cost and there are currently no wound care products
available that have been demonstrated to improve healing, or that are cost effective. There have however been a small
number of studies which have examined the use of platelets or fluid derived from platelets, either from the patients own
blood or from blood bank products. These have suggested some promise, but have suffered from technical difficulties
in making a suitable wound care product or the volume of blood required to derive the product. It is thought that the
reason why they may work is that growth factors released by the platelets may stimulate the wound to heal.
This study will be a formal, randomised controlled trial to assess a new device for creating a wound care product which
is a plug or patch conprising fibrin, white cells and platelets derived from 18 mls of the patients own blood. The
application of this fibrin/white cell/platelet patch to the patients wound on a weekly basis will be compared with usual
best care in patients with hard to heal Diabetic Foot Ulcers in a secondary care setting in 25 centres in the UK,
Denmark and Sweden..

Inclusion criteria:
1.People aged 18 years and over who have diabetes complicated by one or more ulcers of on a foot or both feet below the level of the malleoli, excluding ulcers confined to the interdigital cleft.
2. Those with more than one eligible ulcer will have one ­ -usually the largest or more clinically significant ­ selected at
screening as the index ulcer.
3. Eligible ulcers will be hard-to-heal, meaning that the cross-sectional area will decrease by less than 50 % during a four week runin period.
3. HbA1c 108 mmol/mol at screening
4. The cross-sectional area of the index ulcer will be 50 and 1000 mm2 at the end of the 4 week runin period.
5. The index ulcer will be clinically non-infected according to IDSA criteria
6. Either the ankle-brachial index (ABPI) in the affected limb will be between 0.50 and 1.40 or the dorsalis pedis pulse and/or tibialis posterior pulse will be palpable.
7. Participants will have the capacity to understand study procedures, and will be able to provided written informed
consent.

Exclusion criteria:
1.Haemoglobin concentration Principal Investigator for this trial: Professor William Jeffcoate

Research Ethics Committee Reference: 13/WM/0202

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

H@N: Liberation through technology means more time for direct clinical activity

NUH implemented a novel technological solution to address communication issues outside usual working hours in a highly successful project led by Dominick Shaw and Andrew Fearn. The wireless system has won an innovation award from Cisco. The data from the programme is being used by John Blakey to quantify and compare clinical activity, providing rapid and relevant information to improve services and training. Continue reading

The Extended Biologic Study – The long-term Safety and Efficacy of Biologic Therapies in Children with Rheumatic Diseases

Summary:
This study will document the use of “biologic drugs” in children with Juvenile Idiopathic Arthritis (JIA) to assess their benefit and safety. Examples of these drugs include etanercept, infliximab, adalimumab, anakinra, abatacept and rituximab. A blood or saliva sample from each child will also be stored for future studies (called a “BioBank”) to allow us to test whether there are variations in genes which can predict who will respond and who may get serious side effects. Until the emergence of biologic drugs, treatment options for severe JIA were limited to methotrexate (MTX) and steroids although many children failed to respond adequately or developed side effects. The new biologic drugs have revolutionised the treatment of JIA although they are not a cure and children need longterm treatment. Parents and children ask about side effects and whether or not the treatment will work for them the answer to such questions is currently lacking and the longterm risk of serious adverse events, such as infections or cancers is unknown. There has been a long track record of the use of biologic drugs in adults with rheumatoid arthritis. Increasingly these drugs are being used in children with arthritis. However, other than for the biologic drug etanercept, little information about their longterm effectiveness or safety in children exists. Following ethical approval, this study will follow children with JIA starting biologic drugs (other than etanercept) and record outcomes using data collected in routine clinical practice, such as improvement in arthritis, as well as serious side effects and compare these outcomes with those observed in a group of children receiving the nonbiologic drug, MTX. Access to clinical data and samples in the BioBank will be subject to rigorous security measures and will comply with national regulations for Good Clinical Practice.

Inclusion criteria:
Biologic Exposed cohort: 1. Patients either satisfying the revised ILAR classification criteria for Juvenile Idiopathic Arthritis (JIA) at the time of registration or diagnosed with JIA by the consultant rheumatologist 2. About to start therapy with a biologic drug, 3. Time from start of biologic agent to enrolment Exclusion criteria:
There are no specific exclusion criteria.

Principal Investigator for this trial: Dr Satyapal Rangaraj

Research Ethics Committee Reference: 09/H1008/137

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

The Extended Biologic Study – The long-term Safety and Efficacy of Biologic Therapies in Children with Rheumatic Diseases

Summary:
This study will document the use of “biologic drugs” in children with Juvenile Idiopathic Arthritis (JIA) to assess their benefit and safety. Examples of these drugs include etanercept, infliximab, adalimumab, anakinra, abatacept and rituximab. A blood or saliva sample from each child will also be stored for future studies (called a “BioBank”) to allow us to test whether there are variations in genes which can predict who will respond and who may get serious side effects. Until the emergence of biologic drugs, treatment options for severe JIA were limited to methotrexate (MTX) and steroids although many children failed to respond adequately or developed side effects. The new biologic drugs have revolutionised the treatment of JIA although they are not a cure and children need longterm treatment. Parents and children ask about side effects and whether or not the treatment will work for them the answer to such questions is currently lacking and the longterm risk of serious adverse events, such as infections or cancers is unknown. There has been a long track record of the use of biologic drugs in adults with rheumatoid arthritis. Increasingly these drugs are being used in children with arthritis. However, other than for the biologic drug etanercept, little information about their longterm effectiveness or safety in children exists. Following ethical approval, this study will follow children with JIA starting biologic drugs (other than etanercept) and record outcomes using data collected in routine clinical practice, such as improvement in arthritis, as well as serious side effects and compare these outcomes with those observed in a group of children receiving the nonbiologic drug, MTX. Access to clinical data and samples in the BioBank will be subject to rigorous security measures and will comply with national regulations for Good Clinical Practice.

Inclusion criteria:
Biologic Exposed cohort: 1. Patients either satisfying the revised ILAR classification criteria for Juvenile Idiopathic Arthritis (JIA) at the time of registration or diagnosed with JIA by the consultant rheumatologist 2. About to start therapy with a biologic drug, 3. Time from start of biologic agent to enrolment Exclusion criteria:
There are no specific exclusion criteria.

Principal Investigator for this trial: Dr Helen E Venning

Research Ethics Committee Reference: 09/H1008/137

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

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