Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial
Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial
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DOI：
10.1016/s2468-1253(19)30198-0
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发表时间：
2019-09-01
影响因子：
35.7
通讯作者：
Keller, Marla J.
中科院分区：
文献类型：
--
作者：
Aroniadis, Olga C.;Brandt, Lawrence J.;Keller, Marla J.
背景粪便微生物群移植（FMT）在缓解肠易激综合征（IBS）症状方面显示出希望;然而，关于该技术的对照数据很少。本临床试验的目的是评估FMT在缓解以腹泻为主的IBS（IBS-D）方面的疗效。方法我们在年龄18-65岁的中重度IBS-D患者中进行了一项双盲、随机、安慰剂对照的交叉试验，该患者的IBS症状严重程度评分（IBS-SSS）超过175，招募自美国三个中心。患者被随机分配（1：1）在四个区组中，使用计算机生成的随机序列接受FMT胶囊，然后是外观相同的安慰剂胶囊，或安慰剂胶囊，然后是FMT胶囊。所有参与者和研究团队成员均对随机化设盲。一名独立的工作人员根据连续编号分配治疗。患者在3天内接受75粒FMT胶囊（每粒胶囊含有约0.38 g最低限度处理的供体粪便）或75粒安慰剂胶囊（每天25粒胶囊）。所有患者在12周时交叉至替代治疗。主要结局是12周时两组IBS-SSS的差异。进行意向治疗分析，所有接受研究药物的患者均纳入不良事件分析。由于中期分析结果显示无效，因此在招募期间终止了试验。该研究注册于ClinicalTrials.gov，编号NCT 02328547。结果从2015年5月28日至2017年4月21日，48名患者被随机分配为先接受FMT（n=25）或先接受安慰剂（n=23）。FMT组有3名参与者失访。在校正基线评分后，12周时FMT接受者（平均221 [SD 105]）和安慰剂接受者（236 [95]）之间的IBS-SSS没有差异（p=0.65）。最常见的药物相关不良事件包括腹痛（接受FMT胶囊的48名参与者中有5名[10%]，接受安慰剂的4名[8%]），恶心（4名[8%] vs 2名[4%]）和腹泻加重（3名[6%] vs 8名[17%]）。1例患者在接受安慰剂胶囊治疗时报告了1例与研究药物无关的严重不良事件（急性胆囊炎），解释FMT是安全的，但与安慰剂相比，在12周时并未引起症状缓解。需要进一步的研究来确定FMT对IBS-D的疗效。版权所有（C）2019 Elsevier Ltd.保留所有权利。
Background Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this dinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D).Methods We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe I BS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0.38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547.Findings From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0.65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules.Interpretation FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D. Copyright (C) 2019 Elsevier Ltd. All rights reserved.