caa a22 4500 445794445 CHVBK 20180317145120.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s10620-011-1653-7 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1653-7 Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn's Disease: A Randomized Placebo-Controlled Trial [Elektronische Daten] [Jill Smith, Sandra Bingaman, Francesca Ruggiero, David Mauger, Aparna Mukherjee, Christopher McGovern, Ian Zagon] 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 12weeks 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 12weeks, 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. Springer Science+Business Media, LLC, 2011 Opioids nationallicence Naltrexone nationallicence IBD nationallicence Mucosal healing nationallicence Smith Jill Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut Bingaman Sandra Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut Ruggiero Francesca Department of Pathology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut Mauger David Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut Mukherjee Aparna Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut McGovern Christopher Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut Zagon Ian Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/7(2011-07-01), 2088-2097 0163-2116 56:7<2088 2011 56 10620 https://doi.org/10.1007/s10620-011-1653-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1653-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Smith Jill Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Bingaman Sandra Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Ruggiero Francesca Department of Pathology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut NATIONALLICENCE 700 1- Mauger David Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut NATIONALLICENCE 700 1- Mukherjee Aparna Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- McGovern Christopher Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Zagon Ian Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/7(2011-07-01), 2088-2097 0163-2116 56:7<2088 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer