PB-18 Probiotic for Mild to Moderate Depression

Official title

A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Evaluate the Efficacy and Safety of Bifidobacterium PB-18 in Adults With Mild to Moderate Depressive Disorder and to Explore Its Gut-Brain Axis Mechanisms

Overview

The goal of this clinical trial is to learn if Bifidobacterium PB-18 can treat mild to moderate depressive disorder in adults aged 18 to 65 years who are not taking antidepressants or other psychotropic medications during the study. It will also learn about the safety of Bifidobacterium PB-18 and explore its potential effects on the gut-brain axis. The main questions it aims to answer are: Does Bifidobacterium PB-18 increase the response rate at Week 8, defined as a reduction of at least 50% from baseline in the 17-item Hamilton Depression Rating Scale (HAMD-17)? What adverse events occur in participants receiving Bifidobacterium PB-18? How do gut microbiota, metabolite profiles, and related biological markers change after treatment with Bifidobacterium PB-18? Researchers will compare Bifidobacterium PB-18 with a placebo, a look-alike powder that does not contain PB-18, to see if Bifidobacterium PB-18 improves depressive symptoms. Participants will: Be randomly assigned to receive Bifidobacterium PB-18 or placebo in a 1:1 ratio Take the assigned study product once daily for 8 weeks Visit the study site at baseline, Week 4, and Week 8 for symptom and safety assessments Complete study questionnaires, including HAMD-17, HAMA, PSQI, and CBCT Provide blood and stool samples at baseline and Week 8 for exploratory biological analyses

Detailed description

This clinical trial is designed to evaluate whether Bifidobacterium PB-18 can improve symptoms in adults with mild to moderate depressive disorder who are not taking antidepressants or other psychotropic medications during the study. The study will also assess the safety of Bifidobacterium PB-18 and explore whether treatment-related changes in gut microbiota, metabolites, and other biological markers may help explain its potential effects through the gut-brain axis.

Depressive disorder is associated with a substantial disease burden, and many people with mild to moderate symptoms are reluctant to start antidepressant treatment because of concerns about adverse effects, delayed onset of action, or long-term medication use. Increasing evidence suggests that the gut-brain axis may play an important role in mood regulation. Bifidobacteria are probiotics that may influence emotional symptoms through effects on neurotransmitter-related pathways, inflammation, and stress responses. Based on preclinical findings and the study rationale described in the protocol, this trial will evaluate PB-18 as a potential non-drug intervention for this patient population.

This is a single-center, randomized, double-blind, placebo-controlled, parallel-group exploratory study. A total of 88 eligible participants will be enrolled and randomly assigned in a 1:1 ratio to receive either Bifidobacterium PB-18 or placebo for 8 weeks. Participants in the active treatment group will take a daily powder containing 1 × 10\^10 colony-forming units of PB-18. Participants in the placebo group will take a matching maltodextrin powder with the same appearance, color, smell, and taste but without PB-18. Study product allocation and coding will be managed independently, and participants, investigators, and outcome assessors will remain blinded during the study.

Eligible participants are adults 18 to 65 years of age who meet DSM-5 diagnostic criteria for depressive disorder and have a baseline HAMD-17 score from 7 to 24. Participants must be willing to complete study visits and must not use antidepressants or other psychotropic medications during the trial. The study includes three visits: baseline, Week 4, and Week 8. At these visits, participants will undergo clinical efficacy and safety assessments, and information on concomitant medications, prohibited medications, and adverse events will be recorded throughout the study.

The main efficacy endpoint is the difference between groups in response rate at Week 8, defined as the proportion of participants with at least a 50% reduction from baseline in the 17-item Hamilton Depression Rating Scale (HAMD-17). Secondary outcomes include remission rate at Week 8, response and remission at Week 4, and changes from baseline in HAMD-17, HAMA, PSQI, and CBCT scores across follow-up visits. Safety will be evaluated by monitoring adverse events and serious adverse events during the study.

To explore potential gut-brain axis mechanisms, blood and stool samples will be collected at baseline and Week 8. These samples will be used for exploratory analyses of gut microbiota, metabolite profiles, and related biological markers, and their relationships with changes in depressive symptoms may also be examined.

Interventions

• Dietary supplement Bifidobacterium
  Participants receive Bifidobacterium PB-18 powder orally once daily for 8 weeks. Each daily dose contains 1 × 10\^10 CFU of PB-18. The study product is administered from baseline through Week 8.
• Other Placebo
  Participants receive a matching placebo powder orally once daily for 8 weeks. The placebo is maltodextrin and matches the PB-18 product in dose schedule, appearance, color, smell, taste, packaging, and administration, but does not contain PB-18.

Primary outcome measures

• Response Rate at Week 8 Based on the 17-Item Hamilton Depression Rating Scale [Time frame: Week 8]

Secondary outcome measures (7)

• Remission Rate at Week 8 Based on the 17-Item Hamilton Depression Rating Scale [Time frame: Week 8]
• Response Rate at Week 4 Based on the 17-Item Hamilton Depression Rating Scale [Time frame: Week 4]
• Remission Rate at Week 4 Based on the 17-Item Hamilton Depression Rating Scale [Time frame: Week 4]
• Change From Baseline in Total Score on the 17-Item Hamilton Depression Rating Scale [Time frame: Baseline, Week 4, and Week 8]
• Change From Baseline in Total Score on the Hamilton Anxiety Rating Scale [Time frame: Baseline, Week 4, and Week 8]
• Change From Baseline in Total Score on the Pittsburgh Sleep Quality Index [Time frame: Baseline, Week 4, and Week 8]
• Change From Baseline in Subscale Scores on the CBCT [Time frame: Baseline, Week 4, and Week 8]

Eligibility criteria

Inclusion criteria

• Outpatient or inpatient participants, aged 18 to 65 years (inclusive), of any sex
• Current episode meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for depressive disorder
• Baseline score on the 17-Item Hamilton Depression Rating Scale is 7 to 24, inclusive
• No concomitant use of antidepressants or other psychotropic medications during the study
• Elementary school education or above, able to understand the study requirements and complete the rating scales
• Participant personally signs the informed consent form and is willing to complete follow-up according to the study protocol

Exclusion criteria

• Current or past diagnosis, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, of bipolar disorder, schizophrenia spectrum and other psychotic disorders, neurocognitive disorders, neurodevelopmental disorders, or substance-related and addictive disorders
• Presence of significant psychotic symptoms, such as delusions or hallucinations
• Severe or unstable diseases of the central nervous system, cardiovascular system, respiratory system, liver, kidneys, endocrine system, hematologic system, or other systems that, in the investigator's judgment, make the participant unsuitable for the study
• Evident suicide risk, defined as a score of 1 or higher on the suicide item of the 17-Item Hamilton Depression Rating Scale
• Active inflammatory disease
• Gastrointestinal infection, tumor, or other organic digestive disease, including but not limited to irritable bowel syndrome, Crohn disease, ulcerative colitis, or celiac disease
• History of major gastrointestinal surgery
• Use of antibiotics, probiotics, prebiotics, or related functional products within 1 month before study entry
• Allergy to the study product or any of its components
• Pregnant or breastfeeding women
• Unable or unwilling to take the study product as required by the protocol
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07562516 · IIT20260039C-R1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗