Imuran Dosing in Crohn's Disease Study

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00113503

Collaborator

Prometheus Laboratories (Industry)

Enrollment

Locations

Arms

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

50 participants

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

Actual Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Azathioprine weight-based dose	Drug: Azathioprine weight-based dose Other Names: Imuran
Experimental: Azathioprine individualised dose	Drug: Azathioprine individualised dose Other Names: Imuran

Arm

Intervention/Treatment

Active Comparator: Azathioprine weight-based dose

Drug: Azathioprine weight-based dose

Other Names:

Imuran

Experimental: Azathioprine individualised dose

Drug: Azathioprine individualised dose

Other Names:

Imuran

Outcome Measures

Primary Outcome Measures

Proportion of subjects achieving clinical remission at week #16. [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 [28 weeks]
Proportion of subjects maintaining clinical remission at week #52 [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	Atlanta Gastroenterology Associates, LLC	Atlanta	Georgia	United States	30342
3	University of Chicago Pediatric Gastroenterology	Chicago	Illinois	United States	60637
4	University of Chicago	Chicago	Illinois	United States	60637
5	Johns Hopkins University	Baltimore	Maryland	United States	21287
6	Duluth Clinic	Duluth	Minnesota	United States	55805
7	Mayo Clinic	Rochester	Minnesota	United States	55905
8	Long Island Clinical Research Assoc.	Great Neck	New York	United States	11021
9	Mt. Sinai Medical Center	New York	New York	United States	10029
10	University of North Carolina Chapel Hill	Chapel Hill	North Carolina	United States	27514
11	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
12	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
13	University of Alberta	Edmonton	Alberta	Canada	T6G2X8
14	London Health Sciences Centre	London	Ontario	Canada	N6A5A5
15	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

ClinicalTrials.gov Identifier:

NCT00113503

Other Study ID Numbers:

DK60083 (terminated)
U01DK060083

First Posted:

Jun 9, 2005

Last Update Posted:

Oct 6, 2017

Last Verified:

Oct 1, 2017

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

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

Azathioprine

Study Results

No Results Posted as of Oct 6, 2017