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Imuran Dosing in Crohn's Disease Study

This study has been terminated.
(Insufficient enrollment)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00113503
First Posted: June 9, 2005
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Prometheus Laboratories
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  Purpose
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.

Condition Intervention Phase
Crohn's Disease Drug: Azathioprine weight-based dose Drug: Azathioprine individualised dose Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-site Trial of Azathioprine Dosing in Crohn's Disease

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 50
Actual Study Start Date: July 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Azathioprine weight-based dose Drug: Azathioprine weight-based dose
Other Name: Imuran
Experimental: Azathioprine individualised dose Drug: Azathioprine individualised dose
Other Name: Imuran

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   10 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00113503


Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Georgia
Atlanta Gastroenterology Associates, LLC
Atlanta, Georgia, United States, 30342
United States, Illinois
University of Chicago Pediatric Gastroenterology
Chicago, Illinois, United States, 60637
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Minnesota
Duluth Clinic
Duluth, Minnesota, United States, 55805
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Long Island Clinical Research Assoc.
Great Neck, New York, United States, 11021
Mt. Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G2X8
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A5A5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Prometheus Laboratories
Investigators
Principal Investigator: Stephen B Hanauer, MD University of Chicago
  More Information

Publications:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00113503     History of Changes
Other Study ID Numbers: DK60083 (terminated)
U01DK060083 ( U.S. NIH Grant/Contract )
First Submitted: June 8, 2005
First Posted: June 9, 2005
Last Update Posted: October 6, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Inflammatory Bowel Disease, Crohn's disease, Crohn's Colitis

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Azathioprine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents