Therapy with the opioid antagonist naltrexone promotes mucosal healing in active
Crohn's disease: a randomized placebo-controlled trial.
Author(s): Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS.
Affiliation(s): Department of Medicine, The Pennsylvania State University, College of Medicine,
GI Medicine H-045, 500 University Drive, Hershey, PA 17033, USA. jsmith2@psu.edu
Publication date & source: 2011, Dig Dis Sci. , 56(7):2088-97
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.
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