Comparison of Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis (METEOR)

February 4, 2015 updated by: Franck Carbonnel, Centre Hospitalier Universitaire de Besancon

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

  • 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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Vienna, Austria, 1090
        • University Hospital of Vienna
      • Bruxelles, Belgium, 1200
        • ULB - Cliniques Saint Luc
      • Amiens, France, 84000
        • CHU Amiens - Hopital NORD
      • Avignon, France, 84000
        • CH Avignon
      • Besançon, France, 25000
        • Centre Hospitalier Universitaire de Besancon
      • Clermont-Ferrand, France, 63000
        • CHU Clermont-Ferrand - Hôpital Hotel Dieu
      • Clichy, France, 92110
        • Aphp - Hopital Beaujon
      • Le Kremlin Bicetre, France, 94270
        • APHP - Hôpital Bicêtre
      • Lille, France, 59037
        • CHRU Lille - Hopital Huriez
      • Nantes, France, 44000
        • CHU NANTES - Hôpital Hôtel Dieu
      • Nice, France, 06202
        • CHU Nice - Hôpital de l'Archet 2
      • Paris, France, 75010
        • APHP - Hopital Saint Louis
      • Paris, France, 75012
        • APHP - Hopital Saint Antoine
      • Paris, France, 75014
        • APHP - Hôpital Cochin
      • Pessac, France, 33604
        • CHU Bordeaux - Hôpital Haut L'Eveque
      • Rouen, France, 76000
        • CHU Rouen - Hôpital Charles Nicolle
      • Saint Priest, France, 42270
        • CHU St Etienne - Hôpital Nord
      • Toulouse, France, 31403
        • CHU Toulouse - Hôpital Rangueil
      • Tel aviv, Israel, 52621
        • Sheba Medical Center
      • Rozzano , Milano, Italy, 20089
        • Istituto Clinico Humanitas
      • San Giovanni Rotondo, Italy, 71013
        • Ospedale Casa Sollievo della Sofferenza
      • Leiden, Netherlands, 2333
        • LUMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • UC diagnosed according to the Lennard-Jones criteria (Appendix 1) with endoscopic colorectal lesions, whatever their extension may be
  • A Mayo Disease Activity Index £ 4, with no item >1 for the clinical part of the score and from 0 to 2 for the endoscopic part at the time of inclusion
  • Steroid-dependence defined by at least 1 unsuccessful attempt to stop systemic steroid therapy during the last 12 weeks. Steroid therapy might have been completely stopped if it has been restarted within the last 30 days
  • To be receiving a treatment of prednisone at a dose between 10 and 40mg, stable for at least 2 weeks at the time of inclusion
  • Under an adequate contraception for male or female subjects of childbearing potential

Exclusion Criteria:

  • Indication to a colectomy.
  • Alcoholism (more than 21 glasses per week for male subjects and 14 glasses per week for female subjects). 1 glass corresponds to 3 cl of strong alcohol, 10 cl glass of wine or a half pint of beer.
  • Pregnant or breast-feeding female subjects.
  • No efficacious contraception.
  • NSAIDS or cotrimoxazole intake upon inclusion, or probenecid intake within 1 month prior to inclusion.
  • Anti-TNFa treatment within 2 months prior to inclusion.
  • Azathioprine, mercaptopurine, cyclosporin or thalidomide within 1 month prior to inclusion.
  • Modification of mesalazine or olsalazine dosage within 1 month prior to inclusion.
  • Chronic (broncho) pneumopathy.
  • Renal failure (creatinaemia > upper limit of normal laboratory values limit).
  • Liver disease apart from primary sclerosing cholangitis.
  • Unexplained rise higher than twice the normal level for transaminases, alkaline phosphatases and/or bilirubin.
  • Folate level < normal level.
  • Past history of malignant condition (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
Methotrexate IM or SC 25 mg/week vs placebo IM or SC for 24 weeks
25 mg per week IM or SC during 24 weeks
Placebo Comparator: 2
1 IM or SC of placebo per week during 24 weeks
one intramuscular injection per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Remission without steroids, immunosuppressives and without colectomy
Time Frame: week 16
week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Franck Carbonnel, CHU Besançon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

July 9, 2007

First Submitted That Met QC Criteria

July 9, 2007

First Posted (Estimate)

July 10, 2007

Study Record Updates

Last Update Posted (Estimate)

February 5, 2015

Last Update Submitted That Met QC Criteria

February 4, 2015

Last Verified

February 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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