The Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Major Depressive Disorder

Sponsor

University of Calgary (Other)

Overall Status

Recruiting

CT.gov ID

NCT04805879

Collaborator

Cumming school of medicine (Other), The W. Garfield Westin Foundation (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary goals of this proof of concept clinical trial are to determine the effectiveness, safety and tolerability of oral FMT in adults with Treatment Resistant Depression (TRD).

Condition or Disease	Intervention/Treatment	Phase
Depression Treatment Resistant Depression	Biological: FMT oral Capsules Biological: Placebo Capsules	Phase 2/Phase 3

Detailed Description

This study is a phase 2/3, double-blinded, randomized controlled trial (RCT) in which 80 adults with TRD being treated with an approved antidepressant medication will be assigned to either FMT capsules or identically appearing placebo capsules. Participant will be followed for f for 14 weeks post FMT. This extended observation period will allow us to see, whether FMT leads to sustainable improvements in depression and changes in intestinal microbiome

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Clinical Trial to Evaluate the Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Major Depressive Disorder

Actual Study Start Date :

Mar 4, 2021

Anticipated Primary Completion Date :

Mar 4, 2023

Anticipated Study Completion Date :

Mar 4, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FMT capsules Each dose of FMT capsules consists of 20 capsules. The 20 over encapsulated capsules are derived from 100 grams of stool and each containing 0.67 ml of pelleted intestinal microbes. PArticipants will recieve a loading dose of 60 capsules over 3 consecutive days followed by a booster dose of 20 caspules 1 month after and a second similar booster dose a month after that	Biological: FMT oral Capsules Each dose of FMT capsules consists of 20 capsules. The 20 over encapsulated capsules are derived from 100 grams of stool donated by a healthy indvidual that was screened to have no mental health issues or chronic or contagious doseases. Each capsule will contain 0.67 ml of pelleted intestinal microbes. Therefore it is considered that the 20 capsules are equivalent to 100 grams of stool
Placebo Comparator: Placebo oral Capsules Placebo casules are inactive capsules that look and weigh the same as the Active FMT caspules. Participants will follow the same schedule as the Active arm.	Biological: Placebo Capsules Placebo Capsules that will look and weigh the same as the FMT oral capsules.

Arm

Intervention/Treatment

Active Comparator: FMT capsules

Each dose of FMT capsules consists of 20 capsules. The 20 over encapsulated capsules are derived from 100 grams of stool and each containing 0.67 ml of pelleted intestinal microbes. PArticipants will recieve a loading dose of 60 capsules over 3 consecutive days followed by a booster dose of 20 caspules 1 month after and a second similar booster dose a month after that

Biological: FMT oral Capsules

Each dose of FMT capsules consists of 20 capsules. The 20 over encapsulated capsules are derived from 100 grams of stool donated by a healthy indvidual that was screened to have no mental health issues or chronic or contagious doseases. Each capsule will contain 0.67 ml of pelleted intestinal microbes. Therefore it is considered that the 20 capsules are equivalent to 100 grams of stool

Placebo Comparator: Placebo oral Capsules

Placebo casules are inactive capsules that look and weigh the same as the Active FMT caspules. Participants will follow the same schedule as the Active arm.

Biological: Placebo Capsules

Placebo Capsules that will look and weigh the same as the FMT oral capsules.

Outcome Measures

Primary Outcome Measures

Change in the MADRS total score [from baseline (pre-intervention) to the final visit (week 13)]
To evaluate the effectiveness of adjunct oral FMT as compared to placebo with currently accepted approved therapy for depression

Secondary Outcome Measures

Side effects as reported on the Toronto Side Effect Scale (TSES) [from baseline (pre-intervention) to the final visit (week 13)]
The tolerability of FMT will be assessed using the Toronto Side effects Scale (TSES)
GI tolerability of patients with Irritable Bowel Syndrome (IBS) [from baseline (pre-intervention) to the final visit (week 13)]
GI tolerability will be assessed using the IBS Symptom Severity Scale (IBS SSS) and IBS specific Quality of Life (IBS-QoL) questionnaire

Other Outcome Measures

To assess the effect of FMT on microbiome profile [from baseline (pre-intervention) to the final visit (week 13)]
Changes will be assessed using next generation sequencing and nuclear magnetic resonance (NMR) spectrometry
changes in inflammatory markers (Blood) [from baseline (pre-intervention) to the final visit (week 13)]
To study the changes in inflammatory markers (blood CRP)
changes in inflammatory markers (stool) [from baseline (pre-intervention) to the final visit (week 13)]
To study the changes in inflammatory markers (fecal calprotectin)
changes in serum cytokines [from baseline (pre-intervention) to the final visit (week 13)]
To study the changes in serum cytokines (IL-6, IL-10, IL-8, IFNγ and TNF)
To examine imaging changes [from baseline (pre-intervention) to the final visit (week 13)]
examine imaging changes via a structural and functional neuroimaging scan associated with FMT

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 18-65 years of age:

Participants should be at least 18 years old and not older than 65 years at the day of screening

Have a primary diagnosis of MDD according to the M.I.N.I. International Neuropsychiatric Interview (MINI)47
Medical history suggestive of Treatment Resistant Depression (TRD). (inadequate response to at least 2 approved antidepressants. at least one of which is in the current episode of depression)48
Have been on a current treatment with a approved antidepressant at an adequate dose for at least 8 weeks
A MADRS score of ≥ 19 at screening and visit 2

Additional Inclusion Criteria:

Participants who will be included in the IBS-D cohort should have a confirmed diagnosis of IBS-D as indicated by the referring gastroenterologist.

Exclusion Criteria:

1. Participant meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5)1 Criteria for the following conditions according to the M.I.N.I: f) Substance Use Disorder within the last 3 months. *(Criteria should include Alcohol and non-alcohol substances except Cannabis) g) Moderate or severe Substance use disorder for Cannabis use the last 3 months h) Active Anorexia Nervosa or Bulimia nervosa i) Schizophrenia or schizoaffective disorder j) Active suicidality 2. Regular intake of non-steroidal anti-inflammatory drugs, antibiotics, or iron supplements for medical purposes in the 3 months prior to study entry 3. Use of prebiotics or probiotics for medical purposes for more than 2 weeks within the last 3 months 4. Clinically diagnosed chronic gastrointestinal diseases (IBD, Crohn's disease, Ulcerative colitis, Celiac disease)

Conditions causing immune suppression 6. Not breastfeeding, pregnant or seeking to get pregnant during the course of this study. Be using an acceptable method of birth control (implants, injectable, combined oral contraceptives, IUDs, sexual abstinence or a vasectomized partner) 7. Reported allergy to Vancomycin or Nitazoxanide