Probiotics and the Gut Brain Axis- Do Probiotics Interact With the Vagal Nerve?

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Dietary Supplement: Multispecies-Probiotic
* Dietary Supplement: Placebo Supplement


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Major Depression receiving a multi-strain probiotic<br>Participants with Major Depression receiving a multi-strain probiotic | Dietary Supplement: Multispecies-Probiotic<br>* 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.<br>* Other names: Omnibiotic-SR;|
| Placebo Comparator: Participants mit Major Depression receiving a placebo<br>Participants mit Major Depression receiving a placebo | Dietary Supplement: Placebo Supplement<br>* Participants in the placebo group receive 2x3 gram of a placebo supplement not containing probiotic strains.<br>* Other names: Placebo;|
| Experimental: Healthy volunteers receiving a multi-strain probiotic<br>Healthy volunteers receiving a multi-strain probiotic | Dietary Supplement: Multispecies-Probiotic<br>* 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.<br>* Other names: Omnibiotic-SR;|
| Placebo Comparator: Healthy volunteers receiving a placebo<br>Healthy volunteers receiving a placebo | Dietary Supplement: Placebo Supplement<br>* Participants in the placebo group receive 2x3 gram of a placebo supplement not containing probiotic strains.<br>* Other names: Placebo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, vagal function, multispecies probiotic, heart rate variability