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.
RCT Entities:
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.
Authors: G D'haens; S Van Deventer; R Van Hogezand; D Chalmers; C Kothe; F Baert; T Braakman; T Schaible; K Geboes; P Rutgeerts Journal: Gastroenterology Date: 1999-05 Impact factor: 22.682
Authors: Jill P Smith; Heather Stock; Sandra Bingaman; David Mauger; Moshe Rogosnitzky; Ian S Zagon Journal: Am J Gastroenterol Date: 2007-01-11 Impact factor: 10.864
Authors: S Kamphuis; F Eriksson; A Kavelaars; J Zijlstra; M van de Pol; W Kuis; C J Heijnen Journal: J Neuroimmunol Date: 1998-04-01 Impact factor: 3.478
Authors: Stefan Schreiber; Paul Rutgeerts; Richard N Fedorak; Munaa Khaliq-Kareemi; Michael A Kamm; Michel Boivin; Charles N Bernstein; Michael Staun; Ole Østergaard Thomsen; Alison Innes Journal: Gastroenterology Date: 2005-09 Impact factor: 22.682
Authors: Paul Rutgeerts; Robert H Diamond; Mohan Bala; Allan Olson; Gary R Lichtenstein; Weihang Bao; Kamlesh Patel; Douglas C Wolf; Michael Safdi; Jean Frederic Colombel; Bret Lashner; Stephen B Hanauer Journal: Gastrointest Endosc Date: 2006-03 Impact factor: 9.427
Authors: L A Dieleman; M J Palmen; H Akol; E Bloemena; A S Peña; S G Meuwissen; E P Van Rees Journal: Clin Exp Immunol Date: 1998-12 Impact factor: 4.330
Authors: L Peyrin-Biroulet; W Sandborn; B E Sands; W Reinisch; W Bemelman; R V Bryant; G D'Haens; I Dotan; M Dubinsky; B Feagan; G Fiorino; R Gearry; S Krishnareddy; P L Lakatos; E V Loftus; P Marteau; P Munkholm; T B Murdoch; I Ordás; R Panaccione; R H Riddell; J Ruel; D T Rubin; M Samaan; C A Siegel; M S Silverberg; J Stoker; S Schreiber; S Travis; G Van Assche; S Danese; J Panes; G Bouguen; S O'Donnell; B Pariente; S Winer; S Hanauer; J-F Colombel Journal: Am J Gastroenterol Date: 2015-08-25 Impact factor: 10.864
Authors: Tia R Bobo; Leo R Fitzpatrick; Tiffany L Whitcomb; Timothy K Cooper; Sorana Raiciulescu; Jill P Smith Journal: Comp Med Date: 2020-01-22 Impact factor: 0.982