Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial

Olga C. Aroniadis, Lawrence J. Brandt, Caterina Oneto, Paul Feuerstadt, Alex Sherman, Allan W. Wolkoff, Zain Kassam, Rotem Gura Sadovsky, Ryan J. Elliott, Shrish Budree, Mimi Kim, Marla J. Keller

Research output: Contribution to journalArticle

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Abstract

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 clinical 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 IBS-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. Funding: National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)675-685
Number of pages11
JournalThe Lancet Gastroenterology and Hepatology
Volume4
Issue number9
DOIs
StatePublished - Sep 1 2019

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Irritable Bowel Syndrome
Diarrhea
Capsules
Randomized Controlled Trials
Placebos
Random Allocation
Fecal Microbiota Transplantation
Medical Futility
Intention to Treat Analysis
Acute Cholecystitis
Lost to Follow-Up
National Institutes of Health (U.S.)
Drug-Related Side Effects and Adverse Reactions
Pharmaceutical Preparations
Cross-Over Studies
Nausea
Abdominal Pain
Tissue Donors
Clinical Trials

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome : a double-blind, randomised, placebo-controlled trial. / Aroniadis, Olga C.; Brandt, Lawrence J.; Oneto, Caterina; Feuerstadt, Paul; Sherman, Alex; Wolkoff, Allan W.; Kassam, Zain; Sadovsky, Rotem Gura; Elliott, Ryan J.; Budree, Shrish; Kim, Mimi; Keller, Marla J.

In: The Lancet Gastroenterology and Hepatology, Vol. 4, No. 9, 01.09.2019, p. 675-685.

Research output: Contribution to journalArticle

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AU - Feuerstadt, Paul

AU - Sherman, Alex

AU - Wolkoff, Allan W.

AU - Kassam, Zain

AU - Sadovsky, Rotem Gura

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