Gastroenterology

Gastroenterology

Volume 149, Issue 1, July 2015, Pages 102-109.e6
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial

https://doi.org/10.1053/j.gastro.2015.04.001Get rights and content

Background & Aims

Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.

Methods

We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the Data Monitoring and Safety Committee, but all patients already enrolled in the trial were allowed to complete the study.

Results

Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%−33%). There was no significant difference in adverse events between groups. Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC ≤1 year entered remission, compared with 6 of 34 of those with UC >1 year (P = .04, Fisher’s exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo (P = .02, Mann-Whitney U test).

Conclusions

FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number: NCT01545908.

Section snippets

Study Design

This is a double-blind randomized controlled trial of FMT vs placebo in active UC conducted in Hamilton Health Sciences, St Joseph’s Healthcare Hamilton, and McMaster University, Hamilton, Canada. The local research ethics committee at McMaster University approved the trial and Health Canada had no objection to the use of FMT for this study. All participants provided written informed consent and an independent Data Monitoring and Safety Committee evaluated the trial annually.

Study Population

Eligible patients

Patients and Termination of the Trial

Patients were recruited during an 18-month period commencing in July 2012. The Data Monitoring and Safety Committee reviewed the data at the approximate 50% recruitment point of the trial and, at that time, there were 4 of 27 patients in remission in the FMT arm and 2 of 26 in the placebo arm. The Data Monitoring and Safety Committee advised that the trial should be discontinued for futility because the primary end point was unlikely to be achieved as specified in the protocol. They also

Discussion

This is the first randomized, placebo-controlled trial, to evaluate the efficacy of FMT in active UC and suggests that this approach induces remission in a statistically significant proportion of cases. FMT may be more efficacious in patients with a recent diagnosis of UC, and this is biologically plausible, as a perturbation in the microbiome might be more easily restored early in the course of the disease. The efficacy of this approach may also be donor dependent and this may explain why some

Acknowledgments

This trial was supported by grants from Hamilton Academic Health Sciences Organization (HAHSO) and Crohn’s and Colitis Canada (CCC). The authors are grateful to Lisa Dunlop and Rita Taraschi for clerical support of the trial and to Dr Ken Croitoru (chair), Josh Neufeld, and Noori Akhtar-Danesh for the services as the Data Monitoring and Safety Committee.

Author contributions: All authors contributed to the design of the study. PM and MW were responsible for the recruitment and assessment of most

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    Conflicts of interest These authors disclose the following: Dr Moayyedi: Chair partly funded by an unrestricted donation given to McMaster University by AstraZeneca; received honoraria for speaking and/or serving on the advisory board for AstraZeneca, Actavis, and Shire Pharmaceuticals. Dr Marshall served as a speaker and/or served on the advisory board for Abbott/Abbvie, Actavis, Aptalis, Ferring, Janssen, Proctor & Gamble, Shire, and Takeda. Dr Reinisch served as a speaker and/or served on the advisory board for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC. Dr Armstrong has received speakers’ fees, consulting fees, research funding, or unrestricted support for educational events from Abbott, Abbvie, Actavis, Aptalis, AstraZeneca, Cook, Cubist, Ferring, Forest, Janssen, Merck, Olympus, Pendopharm, Pentax, Shire, Takeda. and Warner-Chilcott. Dr Kassam was Chief Medical Officer for OpenBiome (after trial was completed). Dr Lee served as a speaker and/or served on the advisory board for Cubist, Merck, and Rebiotix. The remaining authors disclose no conflicts.

    Funding This work was funded by Hamilton Academic Health Sciences Organization (HAHSO) and Crohn’s and Colitis Canada (CCC).

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