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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Franck Carbonnel, Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier:
NCT00498589
First received: July 9, 2007
Last updated: February 4, 2015
Last verified: February 2015
  Purpose
  • 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.

Condition Intervention Phase
Ulcerative Colitis
Drug: methotrexate
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Controlled, Randomized, Double-blind, Multicenter Study, Comparing Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Besancon:

Primary Outcome Measures:
  • Remission without steroids, immunosuppressives and without colectomy [ Time Frame: week 16 ] [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: September 2007
Study Completion Date: June 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498589

Locations
Austria
University Hospital of Vienna
Vienna, Austria, 1090
Belgium
ULB - Cliniques Saint Luc
Bruxelles, Belgium, 1200
France
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 Cochin
Paris, France, 75014
APHP - Hôpital Saint Antoine
Paris, France, 75012
APHP - Hôpital Saint Louis
Paris, France, 75010
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
Israel
Sheba Medical Center
Tel aviv, Israel, 52621
Italy
Istituto Clinico Humanitas
Rozzano , Milano, Italy, 20089
Ospedale Casa Sollievo Della Sofferenza
San Giovanni Rotondo, Italy, 71013
Netherlands
LUMC
Leiden, Netherlands, 2333
Sponsors and Collaborators
Centre Hospitalier Universitaire de Besancon
Investigators
Principal Investigator: Franck Carbonnel CHU Besançon
  More Information

No publications provided

Responsible Party: Franck Carbonnel, PU-PH, Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT00498589     History of Changes
Other Study ID Numbers: GETAID 2006-1
Study First Received: July 9, 2007
Last Updated: February 4, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on August 30, 2015