Probiotics and the Gut Brain Axis- Do Probiotics Interact With the Vagal Nerve? (ProBIO-HRV)

Pilot-study: Probiotics and the Gut Brain Axis- Do Probiotics Interact With the Vagal Nerve? ProBIO-HRV-study

The purpose of this study is to investigate the effects of a multispecies probiotic on the function of the vagal nerve in patients with major depression and healthy participants in a single-center, randomized, placebo-controlled trial.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Dietary supplement: Multispecies-Probiotic; Dietary supplement: Placebo Supplement

Detailed Description

After being informed about the study and potential risks, all participants giving written informed consent will be screened for eligibility for study entry and will be randomized in a double-blind manner to receive either a multistrain probiotic or a placebo for 3 months. At entry, 1 week after inclusion, 4 weeks after inclusion and 3 months (end of study) vagal activity will be measured using a 24hr electrocardiogram.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• informed consenct
• confirmed diagnosis of depression according to ICD-10 or DSM-V
• age between 18 and 65 years

Exclusion Criteria:

• Suicidality
• no informed consent or no ability to provide consent
• cardiovascular disease
• pregnancy, breastfeeding
• alcohol or drug dependency
• other severe psychiatric or organic conditions (epilepsy, brain tumor, recent surgery)
• malignant diseases
• dementia (MMST<20)
• severe autoimmune-disorder or immunosuppression (systemic lupus, HIV, multiple sclerosis)
• antibiotic therapy in the last month
• misuse of laxative
• acute infections
• diarrhoea
• gastrointestinal surgeries (except appendectomy)
• no probiotic intake in the last 6 months
• no regular intake of other supplements, probiotics or antibiotics during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Major Depression receiving a multi-strain probiotic	Dietary supplement: Multispecies-Probiotic; Participants in intervention group receive 2x3g of a multistrain probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W22, Lactobacillus casei W56, Lactobacillus paracasei W20, Lactobacillus plantarum W62, Lactobacillus salivarius W24, Lactococcus lactis W19.; Other Names: Omnibiotic-SR
Placebo Comparator: Participants mit Major Depression receiving a placebo	Dietary supplement: Placebo Supplement; Participants in the placebo group receive 2x3 gram of a placebo supplement not containing probiotic strains.; Other Names: Placebo
Experimental: Healthy volunteers receiving a multi-strain probiotic	Dietary supplement: Multispecies-Probiotic; Participants in intervention group receive 2x3g of a multistrain probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W22, Lactobacillus casei W56, Lactobacillus paracasei W20, Lactobacillus plantarum W62, Lactobacillus salivarius W24, Lactococcus lactis W19.; Other Names: Omnibiotic-SR
Placebo Comparator: Healthy volunteers receiving a placebo	Dietary supplement: Placebo Supplement; Participants in the placebo group receive 2x3 gram of a placebo supplement not containing probiotic strains.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Vagal function	Heart rate variability parameters (logRSA; SDNN)	4 measurements with 24-hr heart rate variability at study entry, one week after, 1 month after and after 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of C-reactive protein (CRP)	CRP is measured from serum samples with a Cobas analyzer.	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Change of Interleukine-6 (IL-6)	IL-6 is measured from serum samples with a Cobas analyzer.	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Change of Oxytocin	Oxytocin will be measured from serum samples using ELISA	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Change of Gut microbiome analysis	16S sequencing of gut microbiome samples, gut microbiota composition will be investigated with QIIME2 and characterized in terms of diversity (alpha-diversity, beta diversity) and differential bacterial abundance between time points.	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Change of Body mass index	Weight will be measured with a calibrated scale, height will be measured with a non expandable tape. BMI will be calculated using the formula [kg/m2].	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Mini-international neuropsychiatric interview (M.I.N.I.)	short structured clinical interview which enables researchers to make diagnoses of psychiatric disorders according to DSM-IV or ICD-10	at study entry
Change in Hamilton Scale for Depression (HAMD)	Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression	4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Beck Depression Inventory (BDI)	21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. The rating is as follows: 0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression	Change in 4 time points at study entry, one week after, 1 month after and 3 months (completion of the study)
Change in Pittsburgh Sleep Quality Inventory (PSQI)	The PSQI is used to rate sleep quality. It includes a scoring key for calculating a patient's seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a "global" score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality.	at study entry, after 7 days, after 4 weeks and after 3 months
Change in Adult Attachment Scale	The scale consists of 18 items scored on a 5 point likert-type scale. It measures adult attachment styles named "Secure", "Anxious" and "Avoidant", defined as: Secure = high scores on Close and Depend subscales, low score on Anxiety subscale; Anxious = high score on Anxiety subscale, moderate scores on Close and Depend subscales; Avoidant = low scores on Close, Depend, and Anxiety subscales	at study entry, after 7 days, after 4 weeks and after 3 months
Change in "Wiener Ernährungsprotokoll"	24-hr food recall	at study entry, after 7 days, after 4 weeks and after 3 months
Change in International Physical Activity Questionnaire	The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients. There are no validated cut-offs.	at study entry, after 7 days, after 4 weeks and after 3 months

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Allergosan

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: depression; heart rate variability; vagal function; multispecies probiotic
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: EK1019/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No