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

Contemp Clin Trials. 2018 Jun:69:40-47. doi: 10.1016/j.cct.2018.04.002. Epub 2018 Apr 5.

Abstract

Background: 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.

Methods: 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 <4 measured using non-invasive vibration-controlled transient elastography and magnetic resonance imaging. Participants will be randomly allocated into three groups: LUB 12 μg, LUB 24 μg, and a placebo group.

Results: The primary endpoint will be changes in alanine aminotransferase from baseline at 12 weeks. The main secondary endpoint will be changes in intestinal permeability from baseline at 12 weeks using the lactulose mannitol ratio.

Conclusions: This study will determine whether LUB improves gut permeability in NAFLD patients with constipation.

Trial registration: This trial is registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000026635).

Keywords: Double blind; Endotoxin; Gut permeability; Lubiprostone; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Placebo controlled; Randomised.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood*
  • Chloride Channel Agonists / administration & dosage
  • Chloride Channel Agonists / adverse effects
  • Constipation* / diagnosis
  • Constipation* / drug therapy
  • Constipation* / etiology
  • Constipation* / metabolism
  • Double-Blind Method
  • Elasticity Imaging Techniques / methods
  • Female
  • Gastrointestinal Tract* / drug effects
  • Gastrointestinal Tract* / metabolism
  • Humans
  • Japan
  • Lubiprostone* / administration & dosage
  • Lubiprostone* / adverse effects
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / physiopathology
  • Outcome Assessment, Health Care
  • Permeability
  • Randomized Controlled Trials as Topic

Substances

  • Chloride Channel Agonists
  • Lubiprostone
  • Alanine Transaminase

Associated data

  • JPRN/UMIN000026635