Scientific Abstract

Proposal No. IBD-0180R
Principal Investigator:  Jill P. Smith, M.D.
Applicant Organization:  The Pennsylvania State University  (Hershey, U.S.A.)
Project Title:   Effects of naltrexone on active Crohn's disease
Period of Award:  August 1, 2006 – February 28, 2009

We have shown in a mouse with chemically-induced colitis that naltrexone significantly decreases inflammation of the bowel and improves the inflammatory index. A pilot study tested the clinical response to oral naltrexone in subjects with active Crohn’s disease and found significant improvement in the Crohn’s Disease Activity Index (CDAI) as well as endoscopic reversal of inflammation. It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn’s disease compared to placebo. In order to test this hypothesis the following specific aims are proposed:

• Evaluate the effects of low dose naltrexone compared to placebo on the activity of Crohn's disease by the following end points: CDAI, pain assessment, laboratory values (CRP and ESR), endoscopic appearance, histology, and quality of life surveys;
• Examine the effects of naltrexone given over three months compared to six months for durability of response;
• Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease; and
• Study the mechanism by which naltrexone exerts its effect by measuring plasma enkephalin levels of subjects on therapy.