Imuran Dosing in Crohn's Disease Study

Study Overview
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Brief Summary
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This study will compare two different dosing methods of azathioprine (IMURAN) in participants with Crohn's disease who are currently taking steroids (e.g. prednisone or budesonide)or who have just started steroids. The study can be up to 54 weeks long. All participants enrolled will receive active drug. Participants will take doses either based upon weight or based on the patient's ability to breakdown the drug (monitored by 6-thioguanine nucleotides (6-TGN) metabolite levels in the blood). All patients enrolled in the study will receive active study drug.

Detailed Description
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This multi-center, double blind (patients and doctors do not know treatment group assignment), randomized (patients are put in 1 of 2 groups) clinical trial which will compare two 52-week-long azathioprine(AZA) dosing methods. The patients enrolled will all be taking steroids (prednisone or budesonide)or have just been prescribed a steroid. The patients will be either in remission on steroids, but cannot taper off without a flare, patients who are on steroids and are still having Crohn's symptoms, or patients who need to start taking steroids. After a two week screening period, patients fitting enrollment criteria will be begin taking study drug. Patients will begin to taper steroids per a set schedule, and taper off steroids completely by week 13. Patients who need to go back on steroids because of returned symptoms are allowed to, per a set schedule in the protocol. Patients will have monthly visits that include physical exams, blood tests and a quality of life questionnaire. Patients will be required to keep a diary of abdominal pain, liquid or soft stools and general well being. After 6 months, only patients in remission (patients not on steroids, and not having active symptoms) will be allowed to continue for last 6 months of the study. Study visits during the last 6 months will be every 2 months, and include physical exams and blood tests, and a quality of life questionnaire. Patients in the study may receive dose changes, and this will require additional blood tests for safety.

Official Title
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A Multi-site Trial of Azathioprine Dosing in Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Azathioprine weight-based dose
* Drug: Azathioprine individualised dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 10-70 years-old., Weigh 20-100 kg (44-220 lbs). CD of the ileum, colon or ileocolon, verified by colonoscopy, barium enema, or small bowel series performed within 36 months Perianal fistulae will be eligible provided that the perianal disease does not account for the preponderance of symptoms. Have steroid-dependent, steroid-refractory or steroid naive CD. Steroid-dependent CD: CDAI or mCDAI of < 150 while receiving prednisone 10-40 mg/day or budesonide 3-9 mg/day for at least 12 weeks prior to screening, but unable to taper prednisone below 10 mg/day or budesonide below 3 mg/day without experiencing a flare within the previous 6 months. Steroids must be at a stable dose for 2 weeks prior to screening (week #-2), prednisone at a dose of 10-40 mg/day and budesonide at a dose of 3-9 mg/day. Steroid-refractory CD: currently moderately active CD (CDAI or mCDAI 200 - 450) despite treatment with 40 kg) or 0.5 mg/kg/day (if weighing 20 mg/day (if weighing prednisone <40 9 mg/day for the previous 4 weeks prior to the screening kg), or budesonide evaluation. Prednisone or budesonide must be at a stable dose for 2 weeks prior to screening (week #-2). Steroid-naïve CD: currently moderately active CD, (CDAI or mCDAI 200 - 450) and one of the following: Despite treatment with aminosalicylates and/or antibiotics for the previous 4 weeks prior to the screening evaluation, who are candidates for prednisone or budesonide. Not currently on therapy, who are candidates for prednisone or budesonide Patients with prior exposure to steroids, who have not been treated with steroids for 4 weeks prior to screening, and are candidates for prednisone or budesonide Prednisone or budesonide will be started at the screening visit, at a dose of 40 mg/day or 9 mg/day and tapered per the steroid taper. Patients who have started steroids up to 14 days prior to screening will also qualify as steroid naïve, however patient needs to be on 40 mg prednisone or 9 mg budesonide. Discontinue oral or rectal 5-Aminosalicylic acid (5-ASA) therapies, rectal steroids, ciprofloxacin or metronidazole at the screening visit. Exclusion Criteria: CDAI > 450 CD requiring hospitalization and intravenous (iv) corticosteroids, iv antibiotics or total parenteral nutrition (TPN). TPN or enteral nutrition of >1000 Calories/day (both TPN and elemental diets impact the CDAI). History of resection of more than 100 cm of small bowel, total proctocolectomy, or subtotal colectomy with ileorectal anastomosis Ileostomy or colostomy Severe fixed symptomatic stenosis of the small or large intestine Blood transfusion within 3 months before screening Treatment with 6-MP or AZA within the 6 months prior to screening Immunosuppressants or biologics 3 months before screening Treatment 2 weeks before screening: Allopurinol; Trimethoprim-sulfamethoxazole; NSAIDs or aspirin >81mg/day; Cholestyramine or other drugs interfering with enterohepatic circulation; Furosemide and thiazide diuretics; Fish-oil preparations. Discontinue use at screening: Oral or rectal 5-ASA, rectal steroids, metronidazole or quinolones Any prior treatment with natalizumab Presence of abnormal laboratory parameters: Carriage of hepatitis B surface antigen or positive hepatitis C antibody Lack of one acceptable form of contraception while receiving AZA Low TPMT activity

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azathioprine weight-based dose<br> | Drug: Azathioprine weight-based dose<br> <br> * Other names: Imuran;|
| Experimental: Azathioprine individualised dose<br> | Drug: Azathioprine individualised dose<br> <br> * Other names: Imuran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving clinical remission at week #16. | For the steroid-dependent subjects, clinical remission was defined as complete withdrawal of corticosteroids, and Crohn's Disease Activity Index (CDAI) score <150 in adults, or modified CDAI (mCDAI) score <150 in children. For the steroid-refractory and the steroid-naıve subjects, clinical remission was defined as CDAI score <150 (or mCDAI <150 in children), and a reduction of at least 70 points from the baseline score (CDAI or mCDAI), and complete withdrawal of corticosteroids. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects maintaining clinical remission at week #28 |  | 28 weeks | 
| Proportion of subjects maintaining clinical remission at week #52 |  | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease, Crohn's disease, Crohn's Colitis