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.
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.
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.
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.
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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This research was supported by NIH DK073614 from the National Institutes of Health and IBD-0180R from the Broad Medical Research Program. The University GCRC was funded by M01 RR010732 & C06-RR016499 grants from the National Institutes of Health.
Conflict of interest
Drs. Smith and Zagon have intellectual property rights and have a patent for the use of naltrexone in IBD. This disclosure was provided to all study participants. The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy endpoints) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician who has no conflict of interest.
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Smith, J.P., Bingaman, S.I., Ruggiero, F. et al. Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial. Dig Dis Sci 56, 2088–2097 (2011). https://doi.org/10.1007/s10620-011-1653-7
- Mucosal healing