Neurocognitive Effects of FMT in MDD Patients With and Without IBS

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05174273
• Other study ID #: IMA-FMT-MDD/IBS-2020
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 6, 2022
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: University of Calgary
• Contact: Stefanie Hassel, PhD
• Phone: 4032106430
• Email: shassel[@]ucalgary.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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."

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Irritable Bowel Syndrome
• Major Depressive Disorder
• Syndrome

Intervention

Biological:
• Fecal Microbiota Transplantation
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.

Locations

Country	Name	City	State
Canada	University of Calgary, TRW building	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
Valerie Taylor

Country where clinical trial is conducted

Canada, 

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Outcome

Type	Measure	Description	Time frame	Safety issue
Other	structural and functional neuroimaging	fMRI to examine brain imaging changes in response to FMT	Baseline to week 13
Primary	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
Primary	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	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
Secondary	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
Secondary	nuclear magnetic resonance (NMR) spectrometry	To assess the effect of FMT on microbiome profile (community structure and functional metagenome).	Baseline to Week 13