Clinical trial NCT03279224: Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder
Official title: A Randomized Controlled Trial of the Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Bipolar Depression
Keywords: Bipolar, Depression, FMT, Microbiome
Lead sponsor: Women's College Hospital
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2017-09-12
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Adults with BD depression being treated with an approved medication will be assigned to either allogenic FMT (from a healthy, screened individual with no personal or family history of an Axis 1 disorder) or autologous FMT (re-infusion of own feces)
Primary purpose: TREATMENT

Brief summary: Every human harbors complex microbial communities (collectively, the human 'microbiome') that cover the skin and the body's mucosal surfaces. There is mounting evidence of an interaction between the intestinal microbiota, the gut, and the central nervous system (CNS) in what is recognized as the microbiome-gut-brain axis. Based on this compelling body of evidence, there is growing enthusiasm for work that is focused on translating this emerging association into novel therapies for psychiatric illness.

Fecal microbiota transplantation(FMT) is a technique in which gut bacteria are transferred from a healthy screened donor to a patient, with the goal to introduce or restore a stable microbial community in the gut.There are no clinical trials examining the impact of FMT on Bipolar Disorder (BD). However, there is biological rationale to support this type of treatment, given the known inflammatory underpinnings of this illness.

The objective of this study is to assess the effectiveness of this very novel therapy targeting the gut-brain axis, FMT, to treat bipolar depression.

Study Hypotheses:

Main hypothesis: FMT from healthy donors to patients with BD depression will improve depression symptoms as an adjunct to approved medication.

Secondary hypotheses:

1. FMT will also reduce anxiety and global function
2. FMT is safe and will be well tolerated by the patients
3. Improvements in clinical parameters will be associated with specific changes in the intestinal microbiome and/or metabolites in stool and serum

Detailed description: The primary goals of this proof of concept study are to determine the effectiveness, safety and tolerability of FMT in adults with BD depression.

Objective 1: To evaluate the effectiveness of the combination of a currently accepted approved therapy for BD depression + FMT in individuals with BD depression. This will be assessed through a change in the Montgomery-Ãsberg Depression Rating Scale (MADRS) total score from baseline (pre-intervention) to the final visit (week 24). The investigators will also assess the proportion of patients withdrawing from study due to inadequate control of depressive symptoms.

Secondary objective 2: To evaluate the effectiveness of FMT on anxiety symptoms and global function/overall improvement in participants with BD depression. Secondary objective 3: To determine the safety and tolerability of FMT in individuals with BD depression. Safety will be evaluated by solicited and unsolicited adverse events, including serious adverse events, throughout the study period. Tolerability will be assessed using the Toronto Side Effect Scale (TSES). This is a 32-item instrument that is designed to establish incidence, frequency, and severity of CNS, gastrointestinal, and sexual side effects.

Secondary objective 4: To assess the effect of FMT on microbiome profile (community structure and functional metagenome) and fecal metabolome. Changes in fecal microbiome profile and fecal metabolome from baseline to the final visit will be assessed using next generation sequencing and nuclear magnetic resonance (NMR) spectrometry, respectively. Changes in mood rating scales will be correlated with a specific microbiome and metabolome signature. Intestinal microbiome and metabolome of healthy donors will also be assessed.

Eligibility criteria: Inclusion Criteria:

1. Between 18-65 years of age
2. Outpatient status
3. Have a diagnosis of bipolar disorder (BD) (type I or II) according to the Mini International Neuropsychiatric Interview (MINI)
4. Have been on a stable first line treatment for BD depression at an adequate dose for at least 8 weeks prior to study entry
5. Suffer from a current depressive episode (Montgomery-Åsberg Depression Rating Scale (MADRS) score at screening and baseline of ≥ 12)

Exclusion Criteria:

1. DSM-IV criteria for substance abuse within the last 6 months or lifetime dependency
2. Active eating disorders
3. Schizophrenia or schizoaffective disorder
4. Current psychotic symptoms
5. A Young Mania Rating Scale (YMRS) score of ≥12 at screening
6. Active suicidality
7. Regular intake of non-steroidal anti-inflammatory drugs or iron supplements in the 3 months prior to study entry
8. Use of prebiotics or probiotics for medical purposes, use of antibiotics or any experimental drug in the 3 months prior to study entry
9. Chronic gastrointestinal diseases
10. Conditions causing immunosuppression
11. A significant bleeding disorder
12. Any contraindication to colonoscopy
13. Pregnancy or breastfeeding

Primary outcomes:
measure: Change in the MADRS total score from baseline (pre-intervention) to the final visit (week 24).
timeFrame: Every 2 weeks for 24 weeks
Secondary outcomes:
measure: Changes in the the Clinical Global Impression (CGI) scale
timeFrame: Every 2 weeks for 24 weeks
measure: Changes in the the World Health Organization Quality of life (WHOQOL-BREF) rating
timeFrame: Every 2 weeks for 24 weeks
measure: Side effects as reported on the Toronto Side Effect Scale (TSES)
timeFrame: Every 2 weeks for 24 weeks
measure: Changes in fecal microbiome profile
timeFrame: stool sample collected at Baseline (Visit 2), week 12 and at week 24
measure: Changes in fecal Metabolome
timeFrame: stool sample collected at Baseline (Visit 2), week 12 and at week 24
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Women's college Research Institute
state: Ontario
Study officials:
affiliation: Women's College Hospital
name: Valerie Taylor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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