NCT00498589

Comparison of Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis

A Controlled, Randomized, Double-blind, Multicenter Study, Comparing Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 110 (actual)
• Sponsor: Centre Hospitalier Universitaire de Besancon · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

* PHASE: II * TYPE OF STUDY : With direct benefit * DESCRIPTIVE: Multicenter, randomized, double-blind study * INCLUSION CRITERIA: Steroid-dependent ulcerative colitis * OBJECTIVES: To show superiority of methotrexate vs placebo in inducing steroid-free remission in steroid-dependent ulcerative colitis * STUDY TREATMENTS: Methotrexate 1 intramuscular injection (25 mg) per week Placebo 1 intramuscular injection per week * NUMBERS OF PATIENTS: 55 patients in each group, i.e. a total of 110 patients * INCLUSION PERIOD: 24 months * STUDY DURATION: 36 months * EVALUATION CRITERIA: Remission without steroids, immunosuppressives and without colectomy at 16 weeks of treatment.

Detailed description

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that slightly reduces life expectancy, strongly reduces its quality and can lead to serious complications such as acute colitis, dysplasia and colon cancer. About 40'000 patients are affected in France Among them, 15% suffer from a chronic active form that often leads to an extended steroid therapy, and its known side effects. Azathioprine has already proven its efficacy in this indication but brings a lasting remission without steroid in only 41% of the patients (1-4). What are the medications available for the patients who failed in maintaining a remission with azathioprine ? Cyclosporin is designed for severe or steroid-resistant forms. (5). The results of two recent studies have showed that infliximab is more efficacious than placebo in active UC (6, 7). Infliximab is expensive, its efficacy in steroid-dependent UC has not been specifically tested yet, and its tolerance on the long term remains uncertain. Methotrexate proved its efficacy in Crohn's disease with an intramuscular dose of 25mg/week (8). In UC a controlled trial has been negative with an oral dose of 12.5mg/week (9). Another study compared mercaptopurine, methotrexate (15mg/week) and 5-aminosalicylate in 72 steroid-dependent patients with CD or UC (10). The remission rates obtained were 58% after 30 weeks with methotrexate (not significantly different from 5-ASA) and 14% after 106 weeks (not significantly different from 5-ASA). Few data are available on the efficacy of methotrexate in UC, at a dose which is active in Crohn's disease (25mg intramuscular/week). Several uncontrolled series have been published, including 91 patients whose remission failed under azathioprine. Methotrexate is cheap and its patent has fallen in the public domain. Only institutional research will be able to finance a study in this new indication. This is a prospective, controlled, randomized, double-blind study of methotrexate with an intramuscular dose of 25mg/week vs placebo in patients with steroid-dependent UC. This multicenter study will take place under the aegis of the Therapeutic Study Group for Inflammatory Digestive Diseases (G.E.T.A.I.D.) and with the help of the gastroenterologists network of the CIC. The issue of this study is important. If the hypothesis is borne out, a cheap, efficacious medication will be available for chronic active UC.

Conditions

• Ulcerative Colitis

Interventions

Type	Name	Description
DRUG	methotrexate	25 mg per week IM or SC during 24 weeks
DRUG	placebo	one intramuscular injection per week

Timeline

• Start date: 2007-09-01
• Primary completion: 2014-02-01
• Completion: 2014-06-01
• First posted: 2007-07-10
• Last updated: 2015-02-05

Locations

22 sites across 6 countries: Austria, Belgium, France, Israel, Italy, Netherlands