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



Status:Completed
Conditions:Colitis, Gastrointestinal
Therapuetic Areas:Gastroenterology
Healthy:No
Age Range:18 - 70
Updated:4/26/2017
Start Date:February 2012
End Date:April 2017

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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.


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 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).

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.
We found this trial at
31
sites
Baltimore, Maryland 20742
(301) 405-1000
Principal Investigator: Mark Flasar, MD
Phone: 410-706-3397
University of Maryland As a globally-connected university offering a world-class education, the University of Maryland...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Vijay Yajnik, MD
Phone: 617-724-3238
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5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: David Rubin, MD
Phone: 773-824-7414
University of Chicago One of the world's premier academic and research institutions, the University of...
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
Principal Investigator: Steven Polyak, MD
Phone: 319-353-7723
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Los Angeles, California 90033
213) 740-2311
Principal Investigator: Caroline Hwang, MD
Phone: 818-331-5695
University of Southern California The University of Southern California is one of the world’s leading...
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: John Valentine, MD
Phone: 801-587-9060
University of Utah Research is a major component in the life of the U benefiting...
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Seattle, Washington 98104
(206) 543-2100
Principal Investigator: Timothy Zisman, MD
Phone: 206-685-3913
Univ of Washington Founded in 1861 by a private gift of 10 acres in what...
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Asheville, North Carolina 28801
Principal Investigator: William Harlan, MD
Phone: 828-254-0881
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Atlanta, Georgia 30308
Principal Investigator: Douglas Wolf, MD
Phone: 404-257-9000
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Chapel Hill, North Carolina 27599
(919) 962-2211
Principal Investigator: Hans Herfarth, MD, PhD
Phone: 919-966-6806
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Nilesh Lodhia, MD
Phone: 843-876-7212
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Charlotte, North Carolina 28207
Principal Investigator: Sanjib Mohanti, MD
Phone: 704-375-9485
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Chevy Chase, Maryland 20815
Principal Investigator: Robert Hardi, MD
Phone: 301-652-5520
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303 East Superior Street
Chicago, Illinois 60611
Principal Investigator: Stephen Hanauer, MD
Phone: 312-695-4513
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10900 Euclid Ave
Cleveland, Ohio 44106
216-368-2000
Principal Investigator: Jeffry Katz, MD
Phone: 216-844-7214
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
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Denver, Colorado 80210
Principal Investigator: Mark Gerich, MD
Phone: 303-724-7875
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Houston, Texas 77030
Principal Investigator: Manreet Kaur, MD
Phone: 713-798-7616
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Indianapolis, Indiana 46202
Principal Investigator: Monika Fischer, MD
Phone: 317-948-9212
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Lebanon, New Hampshire 03756
Principal Investigator: Campbell Levy, MD
Phone: 603-653-3668
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Lexington, Kentucky
859) 257-9000
Principal Investigator: Deborah Flomenhoft, MD
Phone: 859-323-1086
University of Kentucky The University of Kentucky is a public, land grant university dedicated to...
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500 S Preston St
Louisville, Kentucky
(502) 852-5555
Principal Investigator: Gerald Dryden, MD
Phone: 502-852-7407
University of Louisville The University of Louisville is a state supported research university located in...
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Madison, Wisconsin 53792
(608) 263-2400
Principal Investigator: Sumona Saha, MD
Phone: 608-262-5404
University of Wisconsin In achievement and prestige, the University of Wisconsin–Madison has long been recognized...
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Mentor, Ohio 44060
Principal Investigator: Don Brinberg, MD
Phone: 440-205-1225
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New York, New York 10029
Principal Investigator: Bruce Sands, MD
Phone: 212-241-1617
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Novi, Michigan 48377
Principal Investigator: Nirmal Kaur, MD
Phone: 248-344-2357
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: Mark Osterman, MD
Phone: 215-662-8919
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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Plymouth, Minnesota 55446
Principal Investigator: Robert McCabe, MD
Phone: 612-870-5595
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Rochester, Minnesota 55905
Principal Investigator: Edward Loftus, MD
Phone: 507-284-0535
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325 9th Ave
Seattle, Washington 98104
(206) 744-3300
Principal Investigator: Anita Afzali, MD
Phone: 206-685-3913
Harborview Medical Center Harborview Medical Center is the only designated Level 1 adult and pediatric...
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State College, Pennsylvania 16802
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Phone: 717-531-5226
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Winter Park, Florida 32789
Principal Investigator: Ira Shafran, MD
Phone: 407-629-8121
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