Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial

Dig Dis Sci. 2011 Jul;56(7):2088-97. doi: 10.1007/s10620-011-1653-7. Epub 2011 Mar 8.

Abstract

Background: Endogenous opioid peptides have been shown to play a role in the development and/or perpetuation of inflammation. We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease, and antagonism of the opioid-opioid receptor will lead to reversal of inflammation.

Aims: A randomized double-blind placebo-controlled study was designed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn's disease.

Methods: Forty subjects with active Crohn's disease were enrolled in the study. Randomized patients received daily oral administration of 4.5-mg naltrexone or placebo. Providers and patients were masked to treatment assignment. The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn's Disease Activity Index score (CDAI). The secondary outcome included mucosal healing based upon colonoscopy appearance and histology.

Results: Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40% of placebo-treated patients (p = 0.009). After 12 weeks, 78% of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn's disease endoscopy index severity score (CDEIS) from baseline compared to 28% response in placebo-treated controls (p = 0.008), and 33% achieved remission with a CDEIS score <6, whereas only 8% of those on placebo showed the same change. Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo.

Conclusions: Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn's disease compared to placebo-treated controls. Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn's disease.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Colonoscopy
  • Crohn Disease / drug therapy*
  • Fatigue / chemically induced
  • Female
  • Humans
  • Intestinal Mucosa / drug effects*
  • Male
  • Middle Aged
  • Naltrexone / adverse effects
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / therapeutic use*
  • Remission Induction
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Narcotic Antagonists
  • Naltrexone