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Imuran Dosing in Crohn's Disease Study

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ClinicalTrials.gov Identifier: NCT00113503
Recruitment Status : Terminated (Insufficient enrollment)
First Posted : June 9, 2005
Last Update Posted : October 6, 2017
Sponsor:
Collaborator:
Prometheus Laboratories
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information
First Submitted Date  ICMJE June 8, 2005
First Posted Date  ICMJE June 9, 2005
Last Update Posted Date October 6, 2017
Actual Study Start Date  ICMJE July 2005
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2017)
Proportion of subjects achieving clinical remission at week #16. [ Time Frame: 16 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2005)
  • The primary outcome measure will be the proportion of subjects achieving clinical remission at week #16.
  • For the steroid-dependent subjects, clinical remission is 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 subjects, clinical remission is 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.
Change History Complete list of historical versions of study NCT00113503 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2017)
  • Proportion of subjects maintaining clinical remission at week #28 [ Time Frame: 28 weeks ]
  • Proportion of subjects maintaining clinical remission at week #52 [ Time Frame: 52 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2005)
  • Proportion of subjects maintaining clinical remission at week #28
  • Proportion of subjects maintaining clinical remission at week #52
  • Frequency of any adverse events (AE): • Frequency of AEs requiring dose reduction. • Frequency of AEs requiring drug cessation.
  • Corticosteroid use in the two treatment arms.
  • Adult and pediatric health-related quality of life (HRQOL) index scores in the two treatment arms (Inflammatory Bowel Disease Questionnaire (IBDQ) in adults and IMPACT in children).
  • Levels of TPMT at 28 weeks compared to baseline to determine if TPMT activity is induced during therapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imuran Dosing in Crohn's Disease Study
Official Title  ICMJE A Multi-site Trial of Azathioprine Dosing in Crohn's Disease
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Azathioprine weight-based dose
    Other Name: Imuran
  • Drug: Azathioprine individualised dose
    Other Name: Imuran
Study Arms  ICMJE
  • Active Comparator: Azathioprine weight-based dose
    Intervention: Drug: Azathioprine weight-based dose
  • Experimental: Azathioprine individualised dose
    Intervention: Drug: Azathioprine individualised dose
Publications * Dassopoulos T, Dubinsky MC, Bentsen JL, Martin CF, Galanko JA, Seidman EG, Sandler RS, Hanauer SB. Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease. Aliment Pharmacol Ther. 2014 Jan;39(2):163-75. doi: 10.1111/apt.12555. Epub 2013 Nov 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 4, 2017)
50
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
262
Actual Study Completion Date  ICMJE December 2007
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

      1. Despite treatment with aminosalicylates and/or antibiotics for the previous 4 weeks prior to the screening evaluation, who are candidates for prednisone or budesonide.
      2. Not currently on therapy, who are candidates for prednisone or budesonide
      3. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00113503
Other Study ID Numbers  ICMJE DK60083 (terminated)
U01DK060083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE Prometheus Laboratories
Investigators  ICMJE
Principal Investigator: Stephen B Hanauer, MD University of Chicago
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP