Depression, Treatment Resistant Depression
Conditions
Keywords
FMT, Fecal Microbiota Transplantation, Microbiome, gut brain axis, Major depression
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).
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
Interventions
BIOLOGICALFMT 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
BIOLOGICALPlacebo Capsules
Placebo Capsules that will look and weigh the same as the FMT oral capsules.
Sponsors
Cumming school of medicine
The W. Garfield Westin Foundation
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Have a primary diagnosis of MDD according to the M.I.N.I. International Neuropsychiatric Interview (MINI)47 3. 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 4. Have been on a current treatment with a approved antidepressant at an adequate dose for at least 8 weeks 5. 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) 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 |
| 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) |
Countries
Canada
Contacts
Primary ContactAsem Bala, BDS, MSc
Backup ContactVivek Kumar, MBBS
Outcome results
None listed