NCT02957591

Brief Summary

Recent research demonstrates that the composition of the gut microbiome is a master regulator of key neurophysiological processes that are affected in depression. Indeed, contemporary studies showed that faecal microbiota is altered in patients with major depressive disorder (MDD). Furthermore, it has also been shown that supplementation of probiotics ameliorated depressive symptoms in unmedicated patients with mild to moderate depression. However, no study has yet explored the efficacy of a probiotic-based therapy in patients with severe MDD in addition to a standard antidepressant treatment. As dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and adjuvant therapy (in addition to antidepressant treatment) in depression, this project is aimed at investigating for the first time if probiotic supplementation compared to a placebo treatment improves the effect of standard antidepressant medication on depressive symptoms (i.e. better and faster remission) in patients with severe MDD. Furthermore, this study will further test if probiotic supplementation modulates immune signalling and inflammatory processes (macrophage migration inhibitory factor and interleukin 1 beta), hypothalamic-pituitaryadrenal (HPA) axis responses (saliva cortisol), neurogenesis (brain-derived neurotrophic factor (BDNF) expression), the release of appetite-regulating hormones (leptin and ghrelin), the composition of gut microbiota (in particular levels of Enterobacteriaceae, Alistipes and Faecalibacterium) and brain perfusion, structure and activation and if these changes are associated with the probiotic-induced effect on depressive symptoms.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Mar 2017

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 1, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 8, 2016

Completed
5 months until next milestone

Study Start

First participant enrolled

March 24, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 11, 2019

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 3, 2020

Completed
Last Updated

April 23, 2021

Status Verified

April 1, 2021

Enrollment Period

2.7 years

First QC Date

November 1, 2016

Last Update Submit

April 21, 2021

Conditions

Severe Depression

Keywords

Depressionprobiotic supplementationAdjuvant TherapyGut microbiomePsychological functioningBrain imagingBrain-Gut interactionsSleep

Outcome Measures

Primary Outcomes (1)

  • Hamilton Depression Score

    Change from baseline at week four

Secondary Outcomes (16)

  • Brain perfusion

    Change from baseline at week four

  • Brain structure

    Change from baseline at week four

  • Brain activation

    Change from baseline at week four

  • HPA axis function

    Change from baseline at week four

  • Neurogenesis

    Change from baseline at week four

  • +11 more secondary outcomes

Study Arms (2)

Probiotic Group

EXPERIMENTAL

Over a period of 4 weeks, depressive patients will ingest a probiotic food supplementation (Vivomixx®) 4 times a day. Primary and secondary endpoints will be assessed before and after the intervention.

Dietary Supplement: Vivomixx®

Placebo Group

PLACEBO COMPARATOR

Subjects in the placebo group will receive a placebo 4 times a day over 4 weeks. Primary and secondary endpoints will be assessed before and after the intervention.

Other: Placebo

Interventions

Vivomixx®DIETARY_SUPPLEMENT

Streptococcus thermophilus Bifidobacterium breve Bifidobacterium longum Bifidobacterium infantis Lactobacillus acidophilus Lactobacillus plantarum Lactobacillus paracasei Lactobacillus delbrueckii subsp. bulgaricus

Probiotic Group
PlaceboOTHER

Subjects in the placebo group will receive a placebo that contains starch but no bacteria. The appearance of the placebo will be indistinguishable in color, shape, size, packaging, smell, and taste from that of the probiotic supplement.

Placebo Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18.
  • Mild depression (Hamilton Depression Rating Scale (HAM-D) \> 7).
  • Inpatient with antidepressant treatment at the UPK Basel.
  • Treatment as usual for depression

You may not qualify if:

  • Comorbid psychiatric disturbances such as substance abuse disorder, bipolar disorder, schizophrenia.
  • Current medical conditions such as acute infectious disease, dietary restrictions.
  • Immunosuppressed patients
  • Pregnancy, breast-feeding.
  • Inability to read and understand the participant's information.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Psychiatric Clinics (UPK)

Basel, 4012, Switzerland

Location

Related Publications (3)

  • Sempach L, Doll JPK, Limbach V, Marzetta F, Schaub AC, Schneider E, Kettelhack C, Mahlmann L, Schweinfurth-Keck N, Ibberson M, Lang UE, Schmidt A. Examining immune-inflammatory mechanisms of probiotic supplementation in depression: secondary findings from a randomized clinical trial. Transl Psychiatry. 2024 Jul 24;14(1):305. doi: 10.1038/s41398-024-03030-7.

    PMID: 39048549DERIVED

  • Schneider E, Doll JPK, Schweinfurth N, Kettelhack C, Schaub AC, Yamanbaeva G, Varghese N, Mahlmann L, Brand S, Eckert A, Borgwardt S, Lang UE, Schmidt A. Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial. J Psychiatry Neurosci. 2023 Jan 18;48(1):E23-E33. doi: 10.1503/jpn.220117. Print 2023 Jan-Feb.

    PMID: 36653035DERIVED

  • Schaub AC, Schneider E, Vazquez-Castellanos JF, Schweinfurth N, Kettelhack C, Doll JPK, Yamanbaeva G, Mahlmann L, Brand S, Beglinger C, Borgwardt S, Raes J, Schmidt A, Lang UE. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial. Transl Psychiatry. 2022 Jun 3;12(1):227. doi: 10.1038/s41398-022-01977-z.

    PMID: 35654766DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehavior

Study Officials

  • André Schmidt, Ph.D.

    University Psychiatric Clinics (UPK)

    PRINCIPAL INVESTIGATOR

  • Laura Mählmann, M.Sc.

    University Psychiatric Clinics (UPK)

    PRINCIPAL INVESTIGATOR

  • Stefan Borgwardt, Professor

    University Psychiatric Clinics (UPK)

    PRINCIPAL INVESTIGATOR

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
Ph.D.

Study Record Dates

First Submitted

November 1, 2016

First Posted

November 8, 2016

Study Start

March 24, 2017

Primary Completion

December 11, 2019

Study Completion

January 3, 2020

Last Updated

April 23, 2021

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)