Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder

NCT03279224 | Unknown Phase 2 DMC

• 1 other identifier: STAN-FMT-WCH-2016
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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

Conditions

Bipolar Depression

Keywords

Bipolar, Depression, FMT, Microbiome

Outcome Measures

Primary Outcomes (1)

• Change in the MADRS total score from baseline (pre-intervention) to the final visit (week 24).

  The MADRS score will be used to assess the effectiveness of the combination of a currently accepted approved therapy plus FMT on depression symptoms. The MADRS score will also help assess the percentage of patients who show inadequate control of depressive symptoms

  Every 2 weeks for 24 weeks

Secondary Outcomes (5)

• Changes in the the Clinical Global Impression (CGI) scale

  Every 2 weeks for 24 weeks

• Changes in the the World Health Organization Quality of life (WHOQOL-BREF) rating

  Every 2 weeks for 24 weeks

• Side effects as reported on the Toronto Side Effect Scale (TSES)

  Every 2 weeks for 24 weeks

• Changes in fecal microbiome profile

  stool sample collected at Baseline (Visit 2), week 12 and at week 24

• Changes in fecal Metabolome

  stool sample collected at Baseline (Visit 2), week 12 and at week 24

Study Arms (2)

Allogenic FMT

ACTIVE COMPARATOR

Participants Randomized to this arm will receive FMT (Fecal Microbiota Transplantation) from a healthy, screened individual with no personal or family history of an Axis 1 disorder.

Biological: Allogenic FMT

Autologous FMT

PLACEBO COMPARATOR

Participants Randomized to this arm will receive FMT (Fecal Microbiota Transplantation) by re-infusion of their own feces donated earlier in the study.

Biological: Autologous FMT

Interventions

Allogenic FMT BIOLOGICAL

Fifty (50) g of screened donor feces will be weighed and homogenized with 30 mL of sterile 0.9 N NaCl + 10% glycerol using a sterile 330 micron micro-filter-separated double-compartment polyethylene bag in the Stomacher® Paddle Blender. 2.The volume of fecal filtrate corresponding to fifty (50) g of donor stools will be transferred into a 50 mL Falcon tube with screw top and frozen at -80oC. 3\. For colonoscopy administration, three (3) Falcon tubes of thawed FMT concentrated will be diluted to a total volume of 300 mL with 0.9N NaCl and will be transported to the endoscopy suite. In the endoscopy suite, the FMT product will be packaged into 6 x 50 ml syringes for patient delivery by colonoscopy.

Allogenic FMT

Autologous FMT BIOLOGICAL

1\. Fifty (50) g of the participant's feces will be weighed and homogenized with 30 mL of sterile 0.9 N NaCl + 10% glycerol using a sterile 330 micron micro-filter-separated double-compartment polyethylene bag in the Stomacher® Paddle Blender. 3.The volume of fecal filtrate corresponding to fifty (50) g of participant's stools will be transferred into a 50 mL Falcon tube with screw top and frozen at -80oC. 3\. For colonoscopy administration, three (3) Falcon tubes of thawed FMT concentrated will be diluted to a total volume of 300 mL with 0.9N NaCl and will be transported to the endoscopy suite. In the endoscopy suite, the FMT product will be packaged into 6 x 50 ml syringes for patient delivery by colonoscopy.

Autologous FMT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Valerie Taylor: lead
• University Health Network, Toronto: collaborator

Study Sites (1)

Women's college Research Institute

Toronto, Ontario, M5G1N8, Canada

Location

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Related Links

• Microbiota Therapeutics Outcomes Program (MTOP)

MeSH Terms

Conditions

Bipolar Disorder; Depression

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Valerie Taylor, MD, PhD

  Women's College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both the patient and the study team (clinical team, study coordinator, data analyst) will be blinded to group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychiatrist-in-Chief

Model Details: 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)

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 12, 2017
• Study Start: January 1, 2018
• Primary Completion: March 15, 2022
• Study Completion: December 31, 2022
• Last Updated: May 4, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Data will be uploaded every 6 months through the study and released Within 4 months
• Access Criteria: Researchers approved for access to NDCT have the ability to download shared data from all clinical trials available in the repository

Locations

CA (1)