Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease in adult patients with constipation: The LUBIPRONE, double-blind, randomised, placebo-controlled study design

• Published in: Contemporary clinical trials 2018-06, Vol.69, p.40-47
• Main Authors: Kessoku, Takaomi, Imajo, Kento, Kobayashi, Takashi, Honda, Yasushi, Kato, Takayuki, Ogawa, Yuji, Tomeno, Wataru, Kato, Shingo, Higurashi, Takuma, Yoneda, Masato, Kirikoshi, Hiroyuki, Kubota, Kazumi, Taguri, Masataka, Yamanaka, Takeharu, Usuda, Haruki, Wada, Koichiro, Saito, Satoru, Nakajima, Atsushi
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Chloride Channel Agonists - administration & dosage; Chloride Channel Agonists - adverse effects; Constipation - diagnosis; Constipation - drug therapy; Constipation - etiology; Constipation - metabolism; Double blind; Double-Blind Method; Elasticity Imaging Techniques - methods; Endotoxin; Female; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - metabolism; Gut permeability; Humans; Japan; Lubiprostone; Lubiprostone - administration & dosage; Lubiprostone - adverse effects; Magnetic Resonance Imaging - methods; Male; Middle Aged; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - physiopathology; Non-alcoholic steatohepatitis; Outcome Assessment, Health Care; Permeability; Placebo controlled; Randomised; Randomized Controlled Trials as Topic
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2018.04.002

This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism. LUB is a type 2 chloride channel activator used as a laxative for the treatment of patients with constipation. LUB suppresses gut permeability induced by non-steroidal anti-inflammatory drugs in healthy volunteers and lowers blood endotoxin levels. There have been no clinical studies of LUB for NAFLD/NASH patients. The study plans to enrol adult patients (20–85 years, planned enrolment, n = 150; planned sample size, n = 120) with NAFLD and constipation, alanine aminotransferase ≥40 IU/L, equivalent steatosis grade ≥1, and equivalent fibrosis stage