Miguel Regueiro, M.D. Chair, Department of Gastroenterology and Hepatology Professor of Medicine, Lerner College of Medicine Cleveland Clinic Cleveland, OH

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

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)

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

 Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease

The purpose of this study is to determine if either a targeted type of talk therapy (Phase I) or medication, Wellbutrin, (Phase II) improve sleep disturbance and/or fatigue in individuals with Inflammatory Bowel Disease (IBD).

Estimated Enrollment: 100
Study Start Date: July 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

 Evaluating a Shared Decision Making Program for Crohn's Disease

Specific Aim: Study the impact of the Crohn's Disease Shared Decision Making Program on patients' treatment choice, persistence with chosen therapy, decision quality, cost of care, and outcomes

Hypothesis: The Crohn's Disease Shared Decision Making Program will help patients understand which treatments are right for them and will lead to a higher acceptance of appropriate therapy, improved persistence with chosen therapy, lower costs and improved clinical outcomes.

To accomplish this aim, Investigators will perform a randomized controlled trial to:

Determine how the shared decision making program influences patients' choice of therapy
Evaluate how the shared decision making program affects persistence with chosen therapy
Determine how the shared decision making program affects decision quality
Determine how the shared decision making program influences cost of care and clinical outcomes

Expected Outcome and Impact: Investigators expect that this program will influence patients' choice of therapy, persistence with their preferred therapy, and lead to improved clinical outcomes. Investigators believe that this product can be successfully operationalized in the clinic to establish a new paradigm of how providers can communicate personalized treatment options to patients across a broad range of diseases.

Estimated Enrollment: 300
Study Start Date: March 2014
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)