Neurocognitive Effects of FMT in MDD Patients With and Without IBS

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

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. Additionally, trial feasibility will be monitored via recruitment rate, study visits adherence and participant retention to inform future trial scalability."

Inclusion Criteria:

1. 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

2. Have a primary diagnosis of MDD as assessed/confirmed by the M.I.N.I. International Neuropsychiatric Interview (MINI)

3. Have had a well-documented inadequate response to at least 2 approved antidepressants

4. A MADRS score of ≥ 19 at screening and visit 2a

5. 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

6. Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity Scoring System (IBS-SSS)

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:

   1. Substance Use Disorder within the last 3 months. *(Criteria should include Alcohol and non-alcohol substances except Cannabis)
   2. Moderate or severe substance use disorder for Cannabis use the last 3 months
   3. Active Anorexia Nervosa or Bulimia nervosa
   4. Schizophrenia, schizoaffective or bipolar disorder
   5. Active suicidality

2. Regular intake of non-steroidal anti-inflammatory drugs, antibiotics, or iron supplements for medical purposes in the three (3) months prior to study entry

3. Use of prebiotics or probiotics for medical purposes for more than two (2) weeks within the last three (3) months

4. Conditions causing immunosuppression

5. 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)