Lay Summary

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

The treatment of IBD always has been directed toward the inflammation. Drugs (e.g., steroids or azathioprine) are used to decrease the inflammatory response in the bowel by suppressing the patient’s immune system. Most recently, a specific antibody has been developed called anti-tumor necrosis factor (TNF), and a new era of treatment is arising to combat specific inflammatory agents. These medications are however extremely expense and may have side effects.

Opioids (enkephalins and endorphins) have also been found to have immunologic properties, and infusions of these compounds have been utilized in subjects with AIDS and cancer to improve immune function. Recently, a drug that increases endogenous enkephalin levels has been successfully used in Europe to treat cholera-toxin induced diarrhea and AIDS-associated diarrhea with success. We have shown in animals that low doses of a compound naltrexone, a drug approved for systemic use by the FDA, stimulates the production of elevated tissue levels of enkephalins/endorphins and opioid receptors. We have also showed, in a small number of patients with active Crohn’s disease, that naltrexone improved inflammation scores and possibly promoted mucosal healing. The purpose of this study is to evaluate the effects of low dose naltrexone in a blinded placebo controlled study to determine the safety and efficacy of this compound in those with active Crohn’s disease.

Forty subjects with active Crohn's disease will be treated with either 4.5 mg of naltrexone orally each evening or a placebo. Parameters of measurement include an Activity Index score, laboratory tests, colonoscopies, and quality of life. Subjects will be treated for three or six months. These studies are part of our plans to improve the therapy for Crohn’s disease and lessen the cost and toxicity. Since it is unethical to keep subjects with active Crohn’s disease on a placebo for more than three months, subjects receiving placebo will be rolled over to active drug for the second three-month period and those who flare on placebo will be allowed to roll prematurely into the active arm of the study. The effects of naltrexone will be compared to placebo and treatment for three months will be compared to six months.