Ulcerative ColitisPhase 2METEORNCT00498589
Comparison of Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis
A Phase 2 study testing methotrexate in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Besancon at 22 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 22 sitesin 6 countries
- Study dates
- Sep 2007to Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
France16 sites
CHU Amiens - Hôpital Nord
Amiens, 84000
CH Avignon
Avignon, 84000
Centre Hospitalier Universitaire de Besançon
Besançon, 25000
CHU Clermont-Ferrand - Hôpital Hotel Dieu
Clermont-Ferrand, 63000
APHP - Hôpital Beaujon
Clichy, 92110
APHP - Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
CHRU Lille - Hôpital Huriez
Lille, 59037
CHU Nantes - Hôpital Hôtel Dieu
Nantes, 44000
CHU Nice - Hôpital de l'Archet 2
Nice, 06202
APHP - Hôpital Saint Louis
Paris, 75010
APHP - Hôpital Saint Antoine
Paris, 75012
APHP - Hôpital Cochin
Paris, 75014
CHU Bordeaux - Hôpital Haut L'Eveque
Pessac, 33604
CHU Rouen - Hôpital Charles Nicolle
Rouen, 76000
CHU St Etienne - Hôpital NOrd
Saint-Priest, 42270
CHU Toulouse - Hôpital Rangueil
Toulouse, 31403
Italy2 sites
Istituto Clinico Humanitas
Rozzano , Milano, 20089
Ospedale Casa Sollievo Della Sofferenza
San Giovanni Rotondo, 71013
About this study
Official title: 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.
Read the 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
- Being tested
- methotrexate, placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
25 mg per week IM or SC during 24 weeks
placeboDrug
one intramuscular injection per week
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Methotrexate IM or SC 25 mg/week vs placebo IM or SC for 24 weeks Receives: Drug: methotrexate |
| 2 | Placebo comparator | 1 IM or SC of placebo per week during 24 weeks Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission without steroids, immunosuppressives and without colectomy
Measured: week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2007 (estimated)
- Study startSep 2007
- Primary completionFeb 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Franck Carbonnel, Centre Hospitalier Universitaire de Besancon
- Investigators
- Franck Carbonnel, Principal investigator, CHU Besançon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498589
- Sponsor's protocol ID
- GETAID 2006-1
- Acronym
- METEOR
- Status last verified
- Feb 2015
- First submitted
- 9 Jul 2007
- Last updated
- 5 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Carbonnel F, Colombel JF, Filippi J, Katsanos KH, Peyrin-Biroulet L, Allez M, Nachury M, Novacek G, Danese S, Abitbol V, Bossa F, Moreau J, Bommelaer G, Bourreille A, Fumery M, Roblin X, Reinisch W, Bouhnik Y, Brixi H, Seksik P, Malamut G, Farkkila M, Coulibaly B, Dewit O, Louis E, Deplanque D, Michetti P, Sarter H, Laharie D; European Crohn's and Colitis Organisation; Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives. Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis. Gastroenterology. 2016 Feb;150(2):380-8.e4. doi: 10.1053/j.gastro.2015.10.050. Epub 2015 Nov 26.
PubMed 26632520
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled, Randomized, Double-blind, Multicenter Study, Comparing Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT00498589
- Acronym / sponsor ID
- METEOR / GETAID 2006-1
- Conditions
- Ulcerative Colitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Feb 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 10 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: methotrexateMethotrexate IM or SC 25 mg/week vs placebo IM or SC for 24 weeks |
| 2 | Placebo comparator | Drug: placebo1 IM or SC of placebo per week during 24 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methotrexate25 mg per week IM or SC during 24 weeks | Drug | 1 |
| placeboone intramuscular injection per week | Drug | 2 |
Primary outcome
Remission without steroids, immunosuppressives and without colectomy
Time frame: week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2015.
- Derived from this study: PubMed 26632520Carbonnel F, Colombel JF, Filippi J, Katsanos KH, Peyrin-Biroulet L, Allez M, Nachury M, Novacek G, Danese S, Abitbol V, Bossa F, Moreau J, Bommelaer G, Bourreille A, Fumery M, Roblin X, Reinisch W, Bouhnik Y, Brixi H, Seksik P, Malamut G, Farkkila M, Coulibaly B, Dewit O, Louis E, Deplanque D, Michetti P, Sarter H, Laharie D; European Crohn's and Colitis Organisation; Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives. Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis. Gastroenterology. 2016 Feb;150(2):380-8.e4. doi: 10.1053/j.gastro.2015.10.050. Epub 2015 Nov 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Franck Carbonnel principal investigator
CHU Besançon
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing methotrexate in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Besancon at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in France, Italy, Austria, Belgium, Israel and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission without steroids, immunosuppressives and without colectomy (time frame: week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00498589, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2015.