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

NCT ID: NCT03279224

Last Updated: 2022-05-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2022-12-31

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.

Conditions

Bipolar Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Allogenic FMT

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.

Group Type: ACTIVE_COMPARATOR

Allogenic FMT

Intervention Type: 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.

Autologous FMT

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

Group Type: PLACEBO_COMPARATOR

Autologous FMT

Intervention Type: 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.

Interventions

Allogenic FMT

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.

Intervention Type: BIOLOGICAL

Autologous FMT

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Valerie Taylor

OTHER

Sponsor Role: lead

Responsible Party

Valerie Taylor

Psychiatrist-in-Chief

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Valerie Taylor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Women's College Hospital

Locations

Women's college Research Institute

Toronto, Ontario, Canada

Countries

Canada

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Related Links

https://mtop.ca/funded-projects/

Microbiota Therapeutics Outcomes Program (MTOP)

Other Identifiers

STAN-FMT-WCH-2016

Identifier Type: -

Identifier Source: org_study_id