Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol

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2025

Authors

Fehily, S.R.
Wright, E.K.
Basnayake, C.
Wilson-O'Brien, A.L.
Stanley, A.
Marks, E.P.
Russell, E.E.
Hamilton, A.L.
Bryant, R.V.
Costello, S.P.

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BMJ Open, 2025; 15(4):e094714-1-e094714-10

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Sasha R. Fehily, Emily K. Wright, Chamara Basnayake, Amy L. Wilson-O'Brien, Annalise Stanley, Elise P. Marks, Erin E. Russell, Amy L. Hamilton, Robert V. Bryant, Sam P. Costello, Michael A. Kamm

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Abstract

Introduction: The enteric microbiota drives inflammation in Crohn’s disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn’s disease. The Microbial Restoration (MIRO) study aims to establish this evidence. Methods and analysis: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn’s Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8–16. Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study. The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn’s disease. Ethics and dissemination: Ethical approval has been received by the St Vincent’s Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences. Trial registration number: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.

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© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. Open access This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/.

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