Adjunctive Probiotic Therapy in Major Depressive Disorder: A Randomized Controlled Trial (ProMOOD)

NCT07786285 | Not Yet Recruiting

• 1 other identifier: 162940992
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

depression; probiotics; randomized controlled study

Outcome Measures

Primary Outcomes (1)

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

  12 weeks

Secondary Outcomes (5)

• Change in Beck Depression Inventory-II (BDI-II) score from baseline to Week 12

  12 weeks

• Change in Perceived Stress Scale (PSS-10) score from baseline to Week 12

  12 weeks

• Changes in gut microbiome composition and diversity (α-diversity, β-diversity and relative abundance of bacterial taxa) between baseline and Week 12

  12 weeks

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

  12 weeks

• Less sick leave days corresponding with a change of HAMD-17 score from baseline to 12 weeks

  12 weeks

Study Arms (2)

OMNi-BiOTiC STRESS Repair

EXPERIMENTAL

Stable antidepressant therapy plus OMNi-BiOTiC STRESS Repair for 12 weeks

Dietary Supplement: OMNi-BiOTiC® STRESS Repair

Control group

PLACEBO COMPARATOR

Other: Matched Placebo Powder for Oral Solution

Interventions

OMNi-BiOTiC® STRESS Repair DIETARY_SUPPLEMENT

Participants will receive one 3-g sachet orally once daily 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.

OMNi-BiOTiC STRESS Repair

Matched Placebo Powder for Oral Solution OTHER

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

Control group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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)

You may not qualify if:

• \- 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

Sponsors & Collaborators

• University Maribor: lead
• Institut AllergoSan: collaborator

Study Sites (1)

Zdravstveni dom Gornja Radgona

Gornja Radgona, 9250, Slovenia

Location

Related Publications (2)

• Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817.

  PMID: 37314797 BACKGROUND

• Morkl S, Narrath M, Schlotmann D, Sallmutter MT, Putz J, Lang J, Brandstatter A, Pilz R, Karl Lackner H, Goswami N, Steuber B, Tatzer J, Lackner S, Holasek S, Painold A, Jauk E, Wenninger J, Horvath A, Spicher N, Barth A, Butler MI, Wagner-Skacel J. Multi-species probiotic supplement enhances vagal nerve function - results of a randomized controlled trial in patients with depression and healthy controls. Gut Microbes. 2025 Dec;17(1):2492377. doi: 10.1080/19490976.2025.2492377. Epub 2025 Apr 29.

  PMID: 40298641 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Solutions

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Central Study Contacts

Tomo Brus Hladen, MD

CONTACT

00386 2 62 10 743; tomo.brus.hladen@zd-gr.si

Andreja Čelofiga, PhD, MD

CONTACT

00386 2 321 1115; andreja.celofiga@ukc-mb.si

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: One group receiving the probiotics, the other placebo. Both groups will receive probiotics/placebo from the psychiatrist, they will look and taste the same and non of them will know what the specific patient received.

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: August 25, 2026

Record last verified: 2026-08

Locations

SL (1)