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
Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Contemp Clin Trials. 2018 Jun;69:40-47. doi: 10.1016/j.cct.2018.04.002. Epub 2018 Apr 5.
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 <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.
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.
This study will determine whether LUB improves gut permeability in NAFLD patients with constipation.
This trial is registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000026635).
本文报告了一项随机、双盲、安慰剂对照研究的方案，旨在测试鲁比前列酮（LUB）与安慰剂相比，在抑制非酒精性脂肪性肝病（NAFLD）合并便秘患者肠道通透性方面的疗效、安全性和耐受性。NAFLD，包括非酒精性脂肪性肝炎（NASH），是一种常见的慢性肝脏疾病。疾病进展与肠道通透性增加和肠道源性内毒素有关。大多数NAFLD/NASH临床试验药物旨在改善肝功能或全身代谢。LUB是一种2型氯离子通道激活剂，用作泻药治疗便秘患者。LUB可抑制健康志愿者中非甾体抗炎药诱导的肠道通透性，并降低血液内毒素水平。目前尚无针对NAFLD/NASH患者使用LUB的临床研究。
该研究计划招募年龄在20 - 85岁之间的成年患者（计划入组人数n = 150；计划样本量n = 120），这些患者患有NAFLD且合并便秘，丙氨酸氨基转移酶≥40 IU/L，使用非侵入性振动控制瞬时弹性成像和磁共振成像测量的等效脂肪变性分级≥1，等效纤维化分期<4。参与者将被随机分为三组：LUB 12μg组、LUB 24μg组和安慰剂组。
主要终点将是12周时丙氨酸氨基转移酶相对于基线的变化。主要次要终点将是使用乳果糖甘露醇比值评估的12周时肠道通透性相对于基线的变化。
本研究将确定LUB是否能改善NAFLD合并便秘患者的肠道通透性。
本试验已在大学医院医学信息网络（UMIN）临床试验注册中心注册（UMIN000026635）。
