Assessment of the Efficacy and Safety of Fecal Microbiota Transplantation (FMT) in Patients With Major Depressive Disorder

Assessment of the Effectiveness and Safety of Fecal Microbiota Transplantation (FMT) in Patients With Major Depressive Disorder Who Do Not Show Early Improvement Following Antidepressant Treatment: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

This study aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in patients with major depressive disorder (MDD) who exhibit suboptimal early response to antidepressant treatment. Additionally, it sought to investigate the impact of FMT on biological indicators, including intestinal microbiota and metabolites, in individuals with MDD

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD); Depression - Major Depressive Disorder
• Intervention / Treatment: Biological: FMT capsule; Drug: Escitalopram (Lexapro); Biological: Corn Starch capsules

Detailed Description

This multicenter, randomized, double-blind, placebo-controlled study aims to compare the efficacy and safety of adjunctive FMT in patients with major depressive disorder (MDD) who show limited response to initial drug therapy.

A total of 600 patients experiencing depressive episodes will be screened, with all receiving escitalopram oxalate for an initial 2-week period. Of these, 214 participants who exhibit suboptimal therapeutic response to early antidepressant treatment will be enrolled and randomized in a 1:1 ratio to either the experimental group or control group.

During the intervention, participants will continue their existing antidepressant regimen and receive a 4-week treatment with either microbiota capsules or placebo. An additional 20-week follow-up assessment will then be conducted to evaluate outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 214
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gang Wang; Phone Number: 86 + 010-86430066

Study Locations

• China
  • Anhui
    • Wuhu, Anhui, China, 241002
      • Recruiting
      • Wuhu Fourth People's Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100088
      • Recruiting
      • Beijing Anding Hospital
      • Contact: Gang Wang; Phone Number: 86 + 010-86430066
  • Guangdong
    • Guangzhou, Guangdong, China, 510450
      • Not yet recruiting
      • Nangfang Hospital Affiliated of Southern Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The First Affiliated Hospital of Hebei Medical University
  • Shandong
    • Jining, Shandong, China, 272000
      • Recruiting
      • Shandong Daizhuang Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital Affiliated of Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300202
      • Recruiting
      • Tianjin Anding Hospital
  • Yunnan
    • Dali, Yunnan, China, 671003
      • Recruiting
      • The Second People's Hospital of Dali Bai Autonomous Prefecture
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (All 8 criterion are met):

• Outpatient or inpatient, aged 18 to 65 years (inclusive), regardless of gender;
• At the start of the screening phase, participants must meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) diagnostic criteria for recurrent major depressive disorder (MDD) or single-episode MDD;
• At the start of the screening phase, participants' score on the 17-item Hamilton Depression Rating Scale (HAMD-17) must be ≥ 17;
• At the start of the screening phase, participants have not been treated with medication for their current depressive episode;
• At the start of the screening phase, participants are intended to be treated with a single antidepressant medication, Escitalopram;
• The HAMD-17 score after two weeks of treatment with the maximum tolerated dose of escitalopram was reduced by less than 20% compared with the HAMD-17 score at screening;
• Participants must have an education level above primary school and be able to understand the content of the scale;
• Participants sign the informed consent form.

Exclusion Criteria (Exclude if 1 criterion is met):

• According to DSM-5 criteria, currently or previously diagnosed as bipolar disorder, neurodevelopmental disorder, neurocognitive disorder, schizophrenia spectrum and other psychotic disorders, substance-related and addiction disorders;
• Accompanied by significant psychotic symptoms (delusions, hallucinations, etc.);
• The patient currently has severe or unstable central nervous system, cardiovascular, respiratory, liver, kidney, endocrine, blood system or other system diseases, and the researcher believes that the patient is not suitable for inclusion in this study;
• The patient currently has a serious suicide risk, and the HAMD-17 suicide risk item is ≥3 points;
• Suffering from inflammation-related diseases;
• Suffering from gastrointestinal infections, tumors and other structural abnormalities of the digestive system, including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis, celiac disease, etc.;
• Previous history of gastrointestinal surgery;
• Continuous use of antibiotics, probiotics, prebiotics or traditional Chinese medicine products for medical purposes for more than 2 weeks within 3 months before enrollment in the study;
• Those who are allergic to capsule ingredients and contents;
• Pregnant or lactating patients;
• Patients who are unable (such as difficulty swallowing) or unwilling to swallow capsules;
• Patients who received MECT treatment in the past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escitalopram + FMT; The experimental group will receive escitalopram + FMT capsules (using Oral capsules derived from healthy human fecal microbiota)	Biological: FMT capsule; The experimental group will maintain escitalopram treatment and take 1.0 g of FMT capsules orally with breakfast every day for 4 weeks.; Other Names: FMT; microbiota capsule; Drug: Escitalopram (Lexapro); Both the experimental group and the placebo group were treated with the maximum tolerated dose of escitalopram.; Other Names: Escitalopram
Placebo Comparator: Escitalopram + placebo; The control group will be treated with escitalopram + placebo (using capsules containing only corn starch)	Drug: Escitalopram (Lexapro); Both the experimental group and the placebo group were treated with the maximum tolerated dose of escitalopram.; Other Names: Escitalopram; Biological: Corn Starch capsules; The placebo group will maintain escitalopram treatment and take corn starch capsules 1.0 g orally with breakfast every day for 4 weeks.; Other Names: Corn starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The differences in efficacy(HAMD-17 score reduction rate ≥50%) between the two groups	The Hamilton Depression Rating Scale-17(HAMD-17) was used to assess the severity of depression in patients. If the HAMD-17 score reduction rate was ≥50%, the treatment was considered effective. 4 weeks after 4-week treatments, the differences in the effective rate of treatment between the two groups will be compared.	Baseline, Week 4, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The differences in complete remission rate(HAMD-17 ≤ 7 points) between the two groups	The Hamilton Depression Rating Scale-17 (HAMD-17) was used to assess the severity of depression in patients. 4 weeks after 4-week treatments, the differences in complete remission rate (HAMD-17 ≤ 7 points) between the two groups will be compared.	Baseline, Week 4, Week 8
The differences in effective rate(HAMD-17 score reduction rate ≥50%)	At the end of 4-week treatments, the differences in effective rate(HAMD-17 score reduction rate ≥ 50%) between the two groups will be compared.	Baseline and Week 4
The differences in complete remission rate(HAMD-17 ≤ 7 points) between the two groups	At the end of 4-week treatments, the differences in complete remission rate(HAMD-17 ≤ 7 points) between the two groups will be compared.	Baseline and Week 4
Changes in total score of GAD-7 scale	Changes in the total score of the Generalized Anxiety Disorder-7(GAD-7) scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in total score of QIDS-SR scale	Quick Inventory of Depressive Symptoms-Self Rated(QIDS-SR) is mainly used to assess the severity of depressive symptoms. It includes 9 symptoms for depression diagnosis. QIDS-SR is very sensitive to changes in depressive symptoms. Changes in the total score of QIDS-SR scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
The differences in the reduction scores of the HAMD-17 scale in 4 symptom dimensions	The differences in the reduction scores of the HAMD-17 scale in 4 different symptom dimensions at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) was recorded: depression (1/2/3/7/8 items), anxiety (9/10/11/15/17 items), insomnia (4/5/6 items), and somatic (12/13/14/16 items).	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in total score of GSRS scale	The investigators will use the 7-level rating version of the Gastrointestinal Symptom Rating Scale(GSRS). Changes in the total score of the GSRS scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in total score of SF-12 scale	Changes in the total score of the Short Form 12 Health Survey(SF-12) scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in total score of SDS scale	Changes in the total score of the Sheehan Disability Scale(SDS) scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in total score of PDQ-5D scale	Changes in the total score of the Perceived Deficit Questionnaire for Depression 5-item(PDQ-5D) scale at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes of each subscale of CBCT	Changes of each subscale of the Cognitive Behavioral Assessment Tool(CBCT) at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes of each subscale of CGI	Changes of each subscale of the Clinical Global Impressions(CGI) at each follow-up time (0,4,8 and 20 weeks after 4-weeks treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes of each subscale of PSQI	Changes of each subscale of the Pittsburgh sleep quality index(PSQI) at each follow-up time (0,4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Changes in brain imaging and EEG indicators	Changes in brain imaging and Electroencephalogram(EEG) indicators at each follow-up time (4,8 and 20 weeks after 4-week treatments) will be compared with the total score at baseline.	Baseline, Week 4, Week 8, Week 12, Week 24
Evaluation of the safety of the treatments	The investigators will record any adverse events reported by participants, after treatments at each follow-up time (4,8 and 20 weeks after 4-week treatments).	Baseline, Week 4, Week 8, Week 12, Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore changes in intestinal microbiota and metabolomics indicators related to FMT efficacy	Explore the changes in biological indicators at each follow-up time (0, 4, 8, and 20 weeks after 4-week treatments): Blood test: 1 procoagulant tube (5 ml), 1 PAXgene RNA collection tube (2.5 ml), 2 EDTA anticoagulant tubes (6 ml/tube);; Urine test: 1 urine cup (40 ml);; Feces test: 4 sets of feces samples and 2/3 of the 15 ml feces tube are used for microbiome, metabolome, proteome, transcriptome, epigenome and other omics detection and analysis.	Baseline, Week 4, Week 8, Week 12, Week 24

Collaborators and Investigators

• Sponsor: Gang Wang
• Collaborators: West China Hospital; The First Hospital of Hebei Medical University; Tianjin Anding Hospital; Shandong Daizhuang Hospital; The First Affiliated Hospital, Zhejiang University; Wuhu Fourth People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: major depressive disorder; RCT; microbiome; faecal microbiota transplantation
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Environment and Public Health; Dietary Carbohydrates; Carbohydrates; Amines; Nitriles; Polymers; Macromolecular Substances; Microbiological Phenomena; Biota; Biodiversity; Ecosystem; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Polysaccharides; Glucans; Biological Therapy; Propylamines; Biopolymers; Benzofurans; Escitalopram; Starch; Fecal Microbiota Transplantation; Microbiota
• Other Study ID Numbers: No. 2024-58

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No