Imuran Dosing in Crohn's Disease Study

NCT00113503 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: DK60083 (terminated)U01DK060083
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 15

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.

Conditions

Crohn's Disease

Keywords

Inflammatory Bowel Disease, Crohn's disease, Crohn's Colitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Proportion of subjects maintaining clinical remission at week #28

  28 weeks

• Proportion of subjects maintaining clinical remission at week #52

  52 weeks

Study Arms (2)

Azathioprine weight-based dose

ACTIVE COMPARATOR

Drug: Azathioprine weight-based dose

Azathioprine individualised dose

EXPERIMENTAL

Drug: Azathioprine individualised dose

Interventions

Azathioprine weight-based dose DRUG

Also known as: Imuran

Azathioprine weight-based dose

Azathioprine individualised dose DRUG

Also known as: Imuran

Azathioprine individualised dose

Eligibility Criteria

• Age: 10 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Prometheus Laboratories: collaborator

Study Sites (15)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Atlanta Gastroenterology Associates, LLC

Atlanta, Georgia, 30342, United States

Location

University of Chicago Pediatric Gastroenterology

Chicago, Illinois, 60637, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Duluth Clinic

Duluth, Minnesota, 55805, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Long Island Clinical Research Assoc.

Great Neck, New York, 11021, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Alberta

Edmonton, Alberta, T6G2X8, Canada

Location

London Health Sciences Centre

London, Ontario, N6A5A5, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (1)

• 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.

  PMID: 24237037 RESULT

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Stephen B Hanauer, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2005
• First Posted: June 9, 2005
• Study Start: July 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: October 6, 2017

Record last verified: 2017-10

Locations

US (12); CA (3)