The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial

Noah C A Cooke, Asem Bala, Johane P Allard, Susy Hota, Susan Poutanen, Valerie H Taylor, Noah C A Cooke, Asem Bala, Johane P Allard, Susy Hota, Susan Poutanen, Valerie H Taylor

Abstract

Background: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population.

Methods and design: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months.

Discussion: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression.

Trial registration: Clinical Trials Gov NCT03279224.

Keywords: Bipolar disorder; FMT; Microbiome; Mood.

Conflict of interest statement

The principal investigator and site investigators have no competing interests to declare. The funding agencies had no role in the conduct of the study.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Trial design. Randomization schema of a pilot randomized controlled trial on the feasibility, safety and efficacy of FMT for Bipolar Disorder. FMT, fecal microbiota transplant; MADRS, Montgomery–Asberg Depression Rating Scale; YMRS, Young Mania Rating Scale; STAI, State Trait Anxiety Index; CGI, Clinical Global Impressions; SDS, Sheehan Disability Scale; WHOQOL, World Health Organization Quality of Life; TSES, Toronto Side Effect Scale

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