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Ulcerative ColitisPhase 2Merit-UCNCT01393405

Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis

A Phase 2 study testing Methotrexate in people with Ulcerative Colitis, run by University of North Carolina, Chapel Hill at 31 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

There are fewer therapeutic options for patients with active ulcerative colitis (UC) compared to patients with active Crohn's disease (CD) and the investigators are facing a persistent unmet need for additional effective and affordable therapies for patients with UC. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Ulcerative Colitis
What is being tested?
Methotrexate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
179 participants
Where
31 sitesUnited States
Study dates
Feb 2012to Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent.
  • Man or woman between 18 and 70 years of age.
  • UC diagnosed by routine clinical, radiographic, endoscopic, and pathological criteria.
  • Active UC with a Mayo score of 6 to 12 points and moderate-to severe active disease on sigmoidoscopy (Mayo endoscopic subscore of at least 2)
  • and at least ONE of the following criteria:
  • Steroid dependent UC *
Show all 11Show fewer
  • Primary failure or loss of response to an anti-TNF (infliximab, adalimumab, golimumab) in the past
  • Primary failure or loss of response to vedolizumab in the past
  • Intolerance/failure of azathioprine/6-MP therapy in the past
  • Failure of 5-ASA therapy
  • Steroid dependence is defined as a clinical response to treatment with prednisone 40 to 60 mg/day and relapse within 30 days after prednisone treatment was completed or as a requirement for a daily dosage of not less than 10 mg of prednisone and impossibility of weaning the patient off steroid without clinical relapses (two attempts to discontinue the medication within the preceding six months of the start of the study).

Who cannot join

  • Failure to respond to 40 mg of prednisone or higher/day in the last 2 weeks before inclusion
  • Concomitant use of azathioprine (AZA) or 6-mercaptopurine (6-MP) must be discontinued at least 2 weeks before inclusion into the study (Week 0 visit)
  • Anti-TNF therapy in the 2 weeks before the Week 0 visit
  • Failure of cyclosporine therapy in the previous 6 months prior to Screening visit
  • Patients with serum albumin < 2.5 g/dl at baseline
  • Low serum folate defined as decrease of >10% below normal range
Show all 29Show fewer
  • Patients with WBC< 3.0 x109th/L at baseline
  • Patients with platelet count < 100 x109th/L
  • Patients with an underlying infection with C. difficile at Screening visit
  • Patients with pre-existing hepatic disease
  • Patients with known non-alcoholic fatty liver disease (NAFLD)
  • Patients with known Hepatitis B or Hepatitis C
  • Patients with pre-existing renal dysfunction (creatinine >1.5 mg/dl).
  • Patients with a pre-existing chronic lung disease other than well controlled asthma
  • Patients with interstitial lung disease of unknown cause
  • Patients with a BMI >35
  • Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years - basal cell does not exclude)
  • Existing pregnancy, lactation, or planned pregnancy* (men and women) within the next 12 months. (*Methotrexate should not be used for at least 3 months before planned pregnancy for men and women and should not be used during pregnancy or breast feeding)
  • High alcohol consumption (more than seven drinks per week)
  • Non - steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use for at least 4 days a week each month
  • Continuous treatment with one of the following drugs:
  • Probenecid,
  • Trimethoprim/sulfamethoxazole
  • Sulfasalazine
  • Acitretin
  • Streptozocin
  • Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device {IUD}, hormonal contraception, or other means considered adequate by the responsible investigator) or in males with a child-fathering potential (condoms, or other means considered adequate by the responsible investigator during treatment
  • Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial
  • Well-founded doubt about the patient's cooperation.

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United States31 sites

  • Asheville Gastroenterology Associates

    Asheville, North Carolina, 28801

  • Atlanta Gastroenterology

    Atlanta, Georgia, 30342

  • University of Maryland

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Charlotte Gastroenterology & Hepatology

    Charlotte, North Carolina, 28207

  • Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research

    Chevy Chase, Maryland, 20815

  • Northwestern University

    Chicago, Illinois, 60611

  • The University of Chicago

    Chicago, Illinois, 60637

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • University of Colorado

    Denver, Colorado, 80045

  • Baylor University

    Houston, Texas, 77030

  • Indiana University IU Health

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • Dartmouth College

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Southern California

    Los Angeles, California, 90033

  • University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Great Lakes Gastroenterology

    Mentor, Ohio, 44060

  • Mt Sinai School of Medicine

    New York, New York, 10029

  • Henry Ford Health System

    Novi, Michigan, 48377

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Minnesota Gastroenterology

    Plymouth, Minnesota, 55446

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Utah

    Salt Lake City, Utah, 84132

  • Harborview Medical Center

    Seattle, Washington, 98104

  • University of Washington

    Seattle, Washington, 98195

  • Penn State University

    State College, Pennsylvania, 17033

  • Shafran Gastroenterology

    Winter Park, Florida, 32789

Other trials in United States

About this study

Official title: Randomized, Double Blind, Prospective Trial Investigating the Efficacy of Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis (MEthotrexate Response In Treatment of UC - MERIT-UC)

There are fewer therapeutic options for patients with active ulcerative colitis (UC) compared to patients with active Crohn's disease (CD) and the investigators are facing a persistent unmet need for additional effective and affordable therapies for patients with UC. Methotrexate (MTX) 25 mg once weekly administered subcutaneously (sq) or intramuscularly (im) is an efficient therapy to induce and maintain steroid free remission in patients with CD. To evaluate the efficacy of a similar approach in patients with active ulcerative colitis the investigators conduct a double-blind, placebo controlled, randomized, multicenter, parallel group trial to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once weekly in patients with active UC, who either failed 5-ASA therapy, or are steroid dependent or are intolerant or not responding to azathioprine/6-mercaptopurine therapy or have no response/ lost response to infliximab prior to the study inclusion. The study is designed as a drug withdrawal trial and includes two periods, the Induction Period (week 0-16) and the Maintenance Period (week 17-48). In the open label Induction Period every patient will receive a steroid taper, MTX 25 mg sq once weekly + daily folic acid 1 mg tablets for the induction of clinical response or remission. Patients responding to the open label MTX therapy and being off steroids between week 12-16 will be randomized at week 16 1:1 to Placebo sq once weekly + daily folic acid 1 mg tablets + 2.4 g mesalamine or to MTX 25 mg sq once weekly + daily folic acid 1 mg tablets+ 2.4 g mesalamine. The Specific Aims of the trial are: i) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks; ii) To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks; iii) To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission; iiii) To establish a DNA, plasma and serum library to enable the evaluation of clinical and pharmacogenomic models to predict the response to MTX therapy in patients with UC. With 25-30 participating centers actively enrolling, the investigators anticipate to complete enrollment for this study in a time period of 3 years. Completion of this trial will define the therapeutic value of MTX in UC, potentially changing the current therapeutic strategy in UC.

Being tested
Methotrexate
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

    Also called Placebo

    Induction period (week 1-16) (Open label):

    25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily

    Maintenance period (week 17-48) (Randomization):

    25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine or Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine

Study groups in NCT01393405
Study groupRoleWhat they receive
MethotrexateActive comparator25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Receives: Drug: Methotrexate
PlaceboPlacebo comparatorPlacebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Receives: Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Relapse Free Survival Week 17-48

    Relapse-free survival: Total week 48 Mayo score not exceeding 2 points, with all individual subscores not exceeding 1 point and relapse free survival defined by a numerical stable Mayo score throughout 32 weeks of maintenance therapy without increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) compared to the partial Mayo score of the individual patient at randomization at week 16 and no steroid use or other immunosuppressive medication throughout the 32 week maintenance period.

    Measured: 48 weeks

Secondary outcomes (2)

  1. Mucosal Healing at Week 48.

    Mucosal healing is defined as an absolute Mayo subscore for endoscopy of 0 or 1

    Measured: 48 weeks

  2. Relapse of Disease Between Week 17-48

    Relapse of disease in the Maintenance period as defined as an increase of 3 or more points in the partial Mayo clinic score (excluding sigmoidoscopy) with an absolute clinical Mayo score ≥ 4 or need for retreatment with steroids.

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completionApr 2017
  4. Study completionApr 2017

Resources

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
179 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01393405
Sponsor's protocol ID
09-2044
Other IDs
1U01DK092239-01
Acronym
Merit-UC
Status last verified
Mar 2018
First submitted
11 Jul 2011
Last updated
17 Apr 2018
Data monitoring committee
Yes

Publications

  • Herfarth HH, Osterman MT, Isaacs KL, Lewis JD, Sands BE. Efficacy of methotrexate in ulcerative colitis: failure or promise. Inflamm Bowel Dis. 2010 Aug;16(8):1421-30. doi: 10.1002/ibd.21246.

    PubMed 20186931

  • Herfarth H, Barnes EL, Valentine JF, Hanson J, Higgins PDR, Isaacs KL, Jackson S, Osterman MT, Anton K, Ivanova A, Long MD, Martin C, Sandler RS, Abraham B, Cross RK, Dryden G, Fischer M, Harlan W, Levy C, McCabe R, Polyak S, Saha S, Williams E, Yajnik V, Serrano J, Sands BE, Lewis JD; Clinical Research Alliance of the Crohn's and Colitis Foundation. Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis. Gastroenterology. 2018 Oct;155(4):1098-1108.e9. doi: 10.1053/j.gastro.2018.06.046. Epub 2018 Jun 30.

    PubMed 29964043

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate in people with Ulcerative Colitis, run by University of North Carolina, Chapel Hill at 31 sites in United States.

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 11 inclusion and 29 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 17 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States. 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?

Yes. Results are posted in the registry (first posted 17 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Relapse Free Survival Week 17-48 (time frame: 48 weeks). 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 NCT01393405, which also lists 2 linked publications.

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 17 Apr 2018.

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