Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03279224
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
Valerie Taylor, Women's College Hospital

Tracking Information
First Submitted Date  ICMJE September 5, 2017
First Posted Date  ICMJE September 12, 2017
Last Update Posted Date February 19, 2019
Actual Study Start Date  ICMJE January 1, 2018
Estimated Primary Completion Date September 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
Change in the MADRS total score from baseline (pre-intervention) to the final visit (week 24). [ Time Frame: Every 2 weeks for 24 weeks ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03279224 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Changes in the the Clinical Global Impression (CGI) scale [ Time Frame: Every 2 weeks for 24 weeks ]
    The effectiveness of Approved treatment + FMT in controlling anxiety symptoms and global function/Overall improvement will be assessed through the CGI
  • Changes in the the World Health Organization Quality of life (WHOQOL-BREF) rating [ Time Frame: Every 2 weeks for 24 weeks ]
    The effectiveness of Approved treatment + FMT in improving the quality of life of bipolar depression patients will be assessed through the World Health Organization Quality of life (WHOQOL-BREF) questionnaire.
  • Side effects as reported on the Toronto Side Effect Scale (TSES) [ Time Frame: Every 2 weeks for 24 weeks ]
    The tolerability of FMT will be assessed using the Toronto Side effects Scale (TSES)
  • Changes in fecal microbiome profile [ Time Frame: stool sample collected at Baseline (Visit 2), week 12 and at week 24 ]
    Stool samples will be collected and analysed using next generation sequencing to examine changes in Changes in fecal microbiome profile
  • Changes in fecal Matabolome [ Time Frame: stool sample collected at Baseline (Visit 2), week 12 and at week 24 ]
    Stool samples will be collected and analysed using nuclear magnetic resonance (NMR) spectrometry
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder
Official Title  ICMJE A Randomized Controlled Trial of the Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Both the patient and the study team (clinical team, study coordinator, data analyst) will be blinded to group assignments.
Primary Purpose: Treatment
Condition  ICMJE Bipolar Depression
Intervention  ICMJE
  • Biological: 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.

  • 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.

Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Biological: Allogenic FMT
  • Placebo Comparator: 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.
    Intervention: Biological: Autologous FMT
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 8, 2017)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 20, 2019
Estimated Primary Completion Date September 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Teresa Bianco, BA 416-323-6400 ext 2301 teresa.bianco@wchospital.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03279224
Other Study ID Numbers  ICMJE STAN-FMT-WCH-2016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: both the descriptive and analyzed data, including individual patient data, will be submitted to the National Database for Clinical Trials related to Mental Illness (NDCT), which is part of the National Institute of Mental Health Data Archive (NDA). The data are de-identified and will be made available to qualified researchers, who have to request access to the dataset.
Supporting Materials: Clinical Study Report (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
URL: https://data-archive.nimh.nih.gov/ndct
Responsible Party Valerie Taylor, Women's College Hospital
Study Sponsor  ICMJE Valerie Taylor
Collaborators  ICMJE University Health Network, Toronto
Investigators  ICMJE
Principal Investigator: Valerie Taylor, MD, PhD Women's College Hospital
PRS Account Women's College Hospital
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP