Adjunctive Probiotic Therapy in Major Depressive Disorder (ProMOOD)

Summary

A double-blind, randomized controlled trial (RCT) aimed at evaluating the efficacy of probiotic supplementation in patients undergoing concurrent antidepressant therapy.

The study will also assess gut microbiome composition and function, and correlate microbiome changes with clinical and psychological outcomes.

Participants will be evaluated by a psychiatrist/clinician, alongside standardized psychological assessments at:

* Baseline (inclusion)
* Week 4
* Week 12

The following validated instruments will be used:

* HAM-D - Hamilton Depression Rating Scale (clinician-rated depression severity)
* BDI - Beck Depression Inventory (self-reported severity of depression)
* PSS - Perceived Stress Scale (self-reported stress perception)

Inclusion Criteria

* Age 18-65 years
* Confirmed diagnosis of depression according to ICD 11 (International Classification of Diseases) criteria
* Written informed consent
* Stable antidepressant therapy (same medication for at least 6 weeks to ensure stable clinical response)

Exclusion Criteria

* Acute suicidality
* Severe cardiovascular disease
* Pregnancy or breastfeeding
* Substance/ alcohol abuse
* Severe neurological or systemic disease
* Recent antibiotic use
* Probiotic use in past year
* Treatment resistant depression
* Psychotic depression

Sample Size

* Initial recruitment target: 150-200 participants
* Expected dropout rate: approximately 50%, based on similar studies
* Final expected sample size: \~100 participants
* Sample size calculation based on Nikolova et al., 2023.

Primary outcome Change in Hamilton Depression Rating Scale (HAM-D-17) score from baseline to Week 12.

Secondary outcomes Change in Beck Depression Inventory-II (BDI-II) score from baseline to Week 12. Change in Perceived Stress Scale (PSS-10) score from baseline to Week 12. Changes in gut microbiome composition and diversity (α-diversity, β-diversity and relative abundance of bacterial taxa) between baseline and Week 12.

Safety and tolerability of probiotic supplementation, assessed by adverse events and treatment discontinuation.

Intervention:

OmniBiotic Stress Repair

Microbiome Analysis Subgroup

Stool samples will be collected at:

* Baseline
* 1 month
* 3 months Analysis will follow methodologies similar to Mörkl S et al. (2025).

Remark: Additional sampling at 1 week (as done in the referenced study) is considered unnecessary, as it falls outside routine clinical monitoring.

Antidepressant Strategy

* Include patients receiving SSRI (Selective Serotonin Reuptake Inhibitors) and possibly SNRI (Serotonin-Norepinephrine Reuptake Inhibitors)
* Advantage: broader applicability
* Limitation: increased variability

Conditions

• Depression / Major Depressive Disorder

Interventions

DIETARY_SUPPLEMENT

OMNi-BiOTiC® STRESS Repair

Participants will receive one 3-g sachet orally twice per day for 12 weeks, in addition to their existing stable antidepressant therapy. Each 3-g sachet contains at least 7.5 × 10⁹ viable bacteria from nine strains: Lactobacillus casei W56, Lactobacillus acidophilus W22, Lactobacillus paracasei W20, Bifidobacterium animalis subsp. lactis W51, Lactobacillus salivarius W24, Lactococcus lactis W19, Bifidobacterium animalis subsp. lactis W52, Lactobacillus plantarum W62, and Bifidobacterium bifidum W23. The powder will be mixed with 100-200 mL of water, allowed to activate for at least one minute, stirred again, and consumed, preferably on an empty stomach. Participants will continue the same antidepressant medication and dose throughout the intervention period unless a change is clinically required.

OTHER

Matched Placebo Powder for Oral Solution

Participants will continue stable antidepressant therapy and receive a matched placebo for 12 weeks.

Sponsors & Collaborators

• Institut AllergoSan

  collaborator UNKNOWN

• University Maribor

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-31

Primary Completion

2029-10-31

Completion

2030-10-31

Countries

• Slovenia

Study Locations