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Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis (Merit-UC)

This study is currently recruiting participants.
Verified March 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Hans Herfarth, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01393405
First received: July 11, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Relapse free survival [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Relapse-free survival, comprised of three components: total week 32 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 (2) and no steroid use or other immunosuppressive medication throughout the 32 week maintenance period.


Secondary Outcome Measures:
  • Mucosal healing defined as an absolute subscore for endoscopy of 0 or 1 at week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Relapse of disease [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 220
Study Start Date: February 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methotrexate
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Drug: Methotrexate

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

Placebo Comparator: Placebo
Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Drug: Methotrexate

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


  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 *
  • Primary failure or loss of response to infliximab 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).

Exclusion Criteria:

  • 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
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01393405

Contacts
Contact: Hans Herfarth, MD, PhD 919-966-6806 hherf@med.unc.edu
Contact: Susan Jackson, MS 919-843-9071 susan_jackson@med.unc.edu

  Hide Study Locations
Locations
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80045
Contact: Katelyn Cowan    303-724-7875    KATELYN.COWAN@ucdenver.edu   
Contact: Mark Gerich, MD    (303) 724-1857    Mark.Gerich@ucdenver.edu   
Principal Investigator: Mark Gerich, MD         
United States, Florida
Shafran Gastroenterology Recruiting
Winter Park, Florida, United States, 32789
Contact: Renee DePanicis    407-629-8121    rmdrn74@yahoo.com   
Contact: Ira Shafran, MD    407-629-8121    Iranita@aol.com   
Principal Investigator: Ira Shafran, MD         
United States, Georgia
Atlanta Gastroenterology Recruiting
Atlanta, Georgia, United States, 30342
Contact: Lamia Mereby    404-257-9000    lamia.mereby@atlantagastro.com   
Contact: Doug Wolf, MD    404-257-9000    M4desk@aol.com   
Principal Investigator: Douglas Wolf, MD         
United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Kristi Milam    773-824-7414    kmilam@medicine.bsd.uchicago.edu   
Contact: David Rubin, MD       drubin@medicine.bsd.uchicago.edu   
Principal Investigator: David Rubin, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Betty Musgrave    319-353-7723    betty-musgrave@uiowa.edu   
Contact: Steven Polyak, MD    319-384-3663    steven-polyak@uiowa.edu   
Principal Investigator: Steven Polyak, MD         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Krystal Walton-Davis    859-323-6423    k.davisRN@uky.edu   
Contact: Deborah Flomenhoft, MD       drflom0@email.uky.edu   
Principal Investigator: Deborah Flomenhoft, MD         
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Lisa Hatter    502-852-3383    lisa.hatter@louisville.edu   
Contact: Gerald Dryden, MD    502-852-6992    gerald.dryden@louisville.edu   
Principal Investigator: Gerald Dryden, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Guru Jambaulikar    410-706-3397    gjambaulikar@medicine.umaryland.edu   
Contact: Mark Flasar, MD    410-706-3387    mflasar@umaryland.edu   
Principal Investigator: Mark Flasar, MD         
Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research Recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Alexa White    301-652-5520    alexa.white@capitaldigestivecare.com   
Contact: Robert Hardi, MD    301-652-5520    robert.hardi@metrogastro.com   
Principal Investigator: Robert Hardi, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Melissa Cohen    617-724-3238    MCOHEN4@PARTNERS.ORG   
Contact: Vijay Yajnik, MD    617-726-1306    vyajnik@PARTNERS.ORG   
Principal Investigator: Vijay Yajnik, MD         
United States, Michigan
Henry Ford Health System Recruiting
Novi, Michigan, United States, 48377
Contact: Dana Drysdale    248-344-2357    DDRYSDA1@hfhs.org   
Contact: Nirmal Kaur, MD       NKAUR1@hfhs.org   
Principal Investigator: Nirmal Kaur, MD         
United States, Minnesota
Minnesota Gastroenterology Recruiting
Plymouth, Minnesota, United States, 55446
Contact: Amy Waller    612-870-5595    Amy.Waller@mngastro.com   
Contact: Robert McCabe, MD    (612) 871-1145    RMcCabe@mngastro.com   
Principal Investigator: Robert McCabe, MD         
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Denise Dahle    507-284-0535    Dahle.Denise2@mayo.edu   
Contact: Edward Loftus, MD    507-284-0959    loftus.edward@mayo.edu   
Principal Investigator: Edward Loftus, MD         
United States, Missouri
Center for Digestive and Liver Diseases, Inc. Recruiting
Mexico, Missouri, United States, 65265
Contact: Matt Burkemper    573-581-7196    matt.burkemper@gutdoc.us   
Contact: Glenn Gordon, MD       glgordonmd@gutdoc.us   
Principal Investigator: Glenn Gordon, MD         
United States, New Hampshire
Dartmouth College Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Lisa Mack    603-653-3667    Lisa.Mack@hitchcock.org   
Contact: Campbell Levy, MD    603-650-8101    L.Campbell.Levy@hitchcock.org   
Principal Investigator: Campbell Levy, MD         
United States, New York
Mt Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Ghimja Berhanu    212-241-1617    ghimja.berhanu@mssm.edu   
Contact: Bruce Sands, MD    212-241-4028    bruce.sands@mssm.edu   
Principal Investigator: Bruce Sands, MD         
Beth Israel Medical Center Recruiting
New York City, New York, United States, 10003
Contact: Duyang Kim    212-844-6446    dukim@chpnet.org   
Contact: David Hudesman    (212) 420-4521    DHudesma@chpnet.org   
Principal Investigator: David Hudesman, MD         
United States, North Carolina
Asheville Gastroenterology Associates Recruiting
Asheville, North Carolina, United States, 28801
Contact: Kylee Diaz    828-254-0881 ext 3426    kylee.diaz@ashevillegastro.com   
Contact: William Harlan, MD    (828) 254-0881    wrharlan@gmail.com   
Principal Investigator: William Harlan, MD         
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Hans Herfarth, MD, PhD    919-966-6806    hherf@med.unc.edu   
Contact: Lucy Goble    919-843-8105    lucy_goble@med.unc.edu   
Principal Investigator: Hans Herfarth, MD, PhD         
Charlotte Gastroenterology & Hepatology Recruiting
Charlotte, North Carolina, United States, 28207
Contact: Lori Sell    704-375-9485    Lori.Sell@charlottegastro.com   
Contact: John Hanson, MD    704-375-9485    john.hanson@charlottegastro.com   
Principal Investigator: John Hanson, MD         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Stacy Smith    919-681-9870    stacey.d.smith@duke.edu   
Contact: Nancy McGreal, MD    919-684-1817    nancy.mcgreal@duke.edu   
Principal Investigator: Nancy McGreal, MD         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Lynn Richardson    216-844-7214    Lynn.Richardson@UHhospitals.org   
Contact: Jeffry Katz, MD    216-844-7214    jeffry.katz@uhhospitals.org   
Principal Investigator: Jeffry Katz, MD         
United States, Oregon
The Oregon Clinic - West Hills Gastroenterology Recruiting
Portland, Oregon, United States, 97225
Contact: Sally Murray    503-517-9659    smurray@orclinic.com   
Contact: David Grunkemeier, MD    503-517-9694    dgrunkemeier@orclinic.com   
Principal Investigator: David Grunkemeier, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Susan Parrott    215-662-8919    Susan.Parrott@uphs.upenn.edu   
Contact: Mark Osterman, MD    215-662-8919    Mark.Osterman@uphs.upenn.edu   
Principal Investigator: Mark Osterman, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Kim Goldby-Reffner    412-648-9173    goldbyreffnerka@upmc.edu   
Contact: Miguel Regueiro, MD    412- 648-9083    RegueiroM@dom.pitt.edu   
Principal Investigator: Miguel Regueiro, MD         
Penn State University Recruiting
State College, Pennsylvania, United States, 17033
Contact: Laurie Peiffer    717-531-5226    lpeiffer@psu.edu   
Contact: Emmanuelle Williams, MD    717-531-6770    ewilliams3@hmc.psu.edu   
Principal Investigator: Emmanuel Williams, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Christine Davis    843-876-7212    davisct@musc.edu   
Contact: Nilesh Lodhia, MD    843-876-7233    nlodhia@gmail.com   
Principal Investigator: Nilesh Lodhia, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Eric Howard    615-322-7403    eric.f.howard@vanderbilt.edu   
Contact: David Schwartz, MD    615-936-1745    david.a.schwartz@vanderbilt.edu   
Principal Investigator: David Schwartz, MD         
United States, Texas
Baylor University Recruiting
Houston, Texas, United States, 77030
Contact: Mustafa Noorbhai    713-798-7616    mustafa.noorbhai@bcm.edu   
Contact: Manreet Kaur, MD    713-798-7616    manreet.kaur@bcm.edu   
Principal Investigator: Manreet Kaur, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Cameron Hill    801-587-3608    Cameron.hill@hsc.utah.edu   
Contact: John Valentine    (801) 587-9092    john.valentine@hsc.utah.edu   
Principal Investigator: John Valentine, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Kelly Crowder    206-543-3220    KCrowder@medicine.washington.edu   
Contact: Timothy Zisman    (206) 685-7174    TZisman@medicine.washington.edu   
Principal Investigator: Timothy Zisman, MD         
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53792
Contact: Kelly Richie    608-262-5404    kr2@medicine.wisc.edu   
Contact: Sumona Saha, MD    608-263-1995    ssaha@medicine.wisc.edu   
Principal Investigator: Sumona Saha, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Hans Herfarth, MD, PhD University of North Carolina, Chapel Hill
  More Information

Publications:
Responsible Party: Hans Herfarth, MD, Professor of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01393405     History of Changes
Other Study ID Numbers: 09-2044, 1U01DK092239-01
Study First Received: July 11, 2011
Last Updated: March 6, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 20, 2014