Neurocognitive Effects of FMT in MDD Patients With and Without IBS

Study Overview
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Brief Summary
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This study is a phase 2/3 open-label controlled trial (CT) in which adults with Major Depressive Disorder (MDD) and adults who have MDD plus comorbid Inflammatory Bowel Syndrome (IBS) will be assigned to either receive oral Fecal Microbiota Transplantation (FMT) or to continue with the treatment they are currently receiving in a Treatment As Usual (TAU) arm. An IBS alone group receiving TAU will be recruited as a clinical control group. The primary goals of this study are to determine effectiveness, safety and tolerability of oral FMT in adults with MDD and in MDD who have comorbid IBS. Additional goals are to characterize patterns and progressions of cognitive and neural correlates associated with MDD and with MDD + IBS and to determine if they improve with FMT. It is known that both, individuals with MDD and those with MDD and IBS show cognitive alterations as well as changes in neural structures, but this study is designed to see if those are changed with treatment response to FMT.

Official Title
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Understanding the Neurocognitive Effects of Fecal Microbiota Transplantation in Major Depressive Disorder Patients With and Without Irritable Bowel Syndrome

Conditions
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Major Depressive Disorder, Irritable Bowel Syndrome

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18-60 years of age: Participants should be at least 18 years old and not older than 60 years at the day of screening Have a primary diagnosis of MDD as assessed/confirmed by the M.I.N.I. International Neuropsychiatric Interview (MINI) Have had a well-documented inadequate response to at least 2 approved antidepressants A MADRS score of ≥ 19 at screening and visit 2a Have a comorbid diagnosis of IBS. IBS patients can include any of the following: diarrhea predominant IBS (IBS-D), constipation predominant IBS (IBS-C), IBS with mixed bowel habits (IBS-M), or unclassified with IBS (IBS-U) as confirmed by the referring doctor using ROME III criteria Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity Scoring System (IBS-SSS) Exclusion Criteria: Participant meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5)[1] Criteria for the following conditions according to the M.I.N.I: Substance Use Disorder within the last 3 months. *(Criteria should include Alcohol and non-alcohol substances except Cannabis) Moderate or severe substance use disorder for Cannabis use the last 3 months Active Anorexia Nervosa or Bulimia nervosa Schizophrenia, schizoaffective or bipolar disorder Active suicidality Regular intake of non-steroidal anti-inflammatory drugs, antibiotics, or iron supplements for medical purposes in the three (3) months prior to study entry Use of prebiotics or probiotics for medical purposes for more than two (2) weeks within the last three (3) months Conditions causing immunosuppression Women who are breastfeeding, pregnant or seeking to get pregnant during the course of this study. Not using an acceptable method of birth control (implants, injectable, combined oral contraceptives, IUDs, sexual abstinence or a vasectomized partner)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a phase 2/3 open-label controlled trial (CT) in which adults with MDD with and without IBS who are being treated with an approved antidepressant medication will be assigned to additionally receive either FMT or to continue with their current treatment in a treatment as usual (TAU) arm. An IBS alone group receiving TAU will be recruited as a clinical control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Participants with a confirmed diagnosis of MDD receiving TAU<br>Eligible and consenting patients will be assigned 1:1 to receive either FMT from a healthy donor or continuing on their usual medication for MDD, i.e., treatment as usual (TAU). This arm will continue to receive their usual anti-depressant. | |
| Active Comparator: Participants with a confirmed diagnosis MDD who will receive FMT + TAU<br>Eligible and consenting patients will be assigned 1:1 to receive either FMT from a healthy donor or continuing on their usual medication for MDD, i.e., treatment as usual (TAU). This arm will be assigned to receive FMT provided by healthy donors. | Biological: Fecal Microbiota Transplantation<br>* FMT is a technique in which intestinal microbiota are transferred from a healthy screened donor to a patient, with the goal being to introduce or restore a stable microbial community in the gut.<br>* Other names: FMT;|
| No Intervention: Participants with a confirmed diagnosis of MDD + IBS assigned to continue with TAU<br> | |
| Active Comparator: Participants with a confirmed diagnosis of MDD + IBS assigned to receive FMT + TAU<br> | Biological: Fecal Microbiota Transplantation<br>* FMT is a technique in which intestinal microbiota are transferred from a healthy screened donor to a patient, with the goal being to introduce or restore a stable microbial community in the gut.<br>* Other names: FMT;|
| No Intervention: Participants with a confirmed diagnosis IBS only receiving TAU<br> | |
| No Intervention: Healthy Controls<br>Data from healthy comparison (HC) participants will be drawn from another completed research study. Healthy comparison participants who will best match the patient population enrolled in the current trial and who consented to data sharing will be selected. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Montgomery-Åsberg Depression Rating Scale (MADRS) | a 10-item questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. This will be used to evaluate the effectiveness of adjunct oral FMT as compared to TAU with currently accepted approved therapy for MDD. The MADRS overall score ranges from 0 to 60. Each item yields a score of 0 to 6 and Higher MADRS score indicates more severe depression | Baseline to week 13 | 
| IBS Symptom Severity Scale (IBS-SSS) | The IBS-SSS is a 5-item questionnaire that is used to assess the severity and frequency of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits, and interference with quality of life over the past 10 days. Scores on the IBS-SSS can range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS. | Baseline to week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toronto Side Effect Scale (TSES) | The TSES is a 32-item instrument that is designed to establish incidence, frequency, and severity of CNS, GI, and sexual side effects. For each side effect, frequency and severity are measured on a 5-point scale. intensity is measured by multiplying frequency and severity. | Baseline to Week 13 | 
| IBS specific Quality of Life (IBS-QoL) | is a self-report 34-item instrument used to assess the impact of IBS and its treatment. used to examine GI tolerability in patients with IBS. The individual responses to the 34 items are summed and averaged for a total score and then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS specific quality of life. | Baseline to Week 13 | 
| nuclear magnetic resonance (NMR) spectrometry | To assess the effect of FMT on microbiome profile (community structure and functional metagenome). | Baseline to Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major depression, IBS, Fecal microbiota Transplantation, Gut, Microbiome, fMRI