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

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. Identifier: NCT00498589
Recruitment Status : Completed
First Posted : July 10, 2007
Last Update Posted : February 5, 2015
Information provided by (Responsible Party):
Franck Carbonnel, Centre Hospitalier Universitaire de Besancon

Brief Summary:
  • 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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: methotrexate Drug: placebo Phase 2

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  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Controlled, Randomized, Double-blind, Multicenter Study, Comparing Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis
Study Start Date : September 2007
Actual Primary Completion Date : February 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: 1
Methotrexate IM or SC 25 mg/week vs placebo IM or SC for 24 weeks
Drug: methotrexate
25 mg per week IM or SC during 24 weeks

Placebo Comparator: 2
1 IM or SC of placebo per week during 24 weeks
Drug: placebo
one intramuscular injection per week

Primary Outcome Measures :
  1. Remission without steroids, immunosuppressives and without colectomy [ Time Frame: week 16 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT00498589

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Franck Carbonnel, PU-PH, Centre Hospitalier Universitaire de Besancon Identifier: NCT00498589     History of Changes
Other Study ID Numbers: GETAID 2006-1
First Posted: July 10, 2007    Key Record Dates
Last Update Posted: February 5, 2015
Last Verified: February 2015

Additional relevant MeSH terms:
Colitis, Ulcerative
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors