We propose a prospective placebo controlled study to investigate the safety and efficacy of 25 mg MIX applied subcutaneously once weekly in patients with active UC, who are either 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. In the setting of an implementation-planning (U34) grant we finalized the study protocol and associated formal requirements for this trial. We obtained a lead IRB approval and are currently obtaining IRB approvals of the participating sites. We registered an IND number (108,560) with the FDA and established the study infrastructure for this prospective placebo-controlled multi-center study using the center framework of the Crohn's and Colitis Foundation of America (CCFA) Clinical Research Alliance (CRA).
The Specific Aims of the trial are: 1) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks. 2) To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks. 3) To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission. 4) 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.

Public Health Relevance

Despite MTX being on the market for decades, the therapeutic approach using parenteral administered MTX in patients failing established therapies such as 5-ASA, thiopurines or anti-TNF therapies is pioneering a potential novel therapy. The results of the trial will provide the necessary data for the therapeutic value of MTX in UC patients, which will likely influence the current global therapeutic practice in UC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK092239-02
Application #
8316407
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Program Officer
Serrano, Jose
Project Start
2011-08-15
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$1,670,502
Indirect Cost
$443,742
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599