Mediterranean Diet and the Microbiota Gut Brain Axis in Major Depression

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of a Mediterranean diet on the function of the vagal nerve in patients with depression.

Detailed Description
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After being informed about the study and potential risks, all patients giving written informed consent will be screened for eligibility. Subjects meeting the inclusion criteria will be randomized in a group recieiving a Mediterranean diet (3 mediterranean meals a day) and dietary coaching (1 session per week for 4 weeks) or a group with conventional hospital food and psychoeducation on depression (1 session per week for 4 weeks).

Official Title
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Mediterranean Diet and the Microbiota Gut Brain Axis- Does Diet Interact With the Function of Vagal Nerve in Major Depression?

Conditions
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Depression

Intervention / Treatment
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* Other: Mediterranean Diet
* Other: Normal hospital diet
* Other: dietary coaching
* Other: Psychoeducation on depression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: legally competent persons aged 18-80 years diagnosis of depression according to ICD-10 or DSM. Exclusion Criteria: other neurologic or psychiatric disorders (epilepsy, brain tumor, head injury, head surgery, trauma) drug or alcohol dependency acute suicidality heart disorders, disorders of the circulatory system pregnancy and period of breastfeeding severe mental disability, dementia (MMST<20) autoimmune disorder, severe immunosuppression (Lupus, HIV, multiple sclerosis) therapy with antibiotics in the last month chronic laxative abuse acute infectious diarrhea GI surgeries (except appendectomy) regular intake of probiotics, antibiotics and food supplements (1 month before and during the study) food allergies or other food intolerances which are incompatible with a mediterranean diet vegetarians, vegans

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mediterranean Diet and dietary coaching<br>Patients receive 3 Mediterranean meals a day for 4 weeks and dietary coaching sessions (á 50 minutes once a week for 4 weeks) | Other: Mediterranean Diet<br>* Diet meeting the requirements for mediterranean style (rich in vegetables, fruit, olive oil, fish) (Davis et al., 2015)<br>Other: dietary coaching<br>* dietary coaching<br>|
| Placebo Comparator: Diet as usual and psychoeducation for depression<br>Patients receive normal hospital diet with 3 meals a day for 4 weeks and psychoeducation sessions (á 50 minutes once a week for 4 weeks) | Other: Normal hospital diet<br>* Normal hospital diet<br>Other: Psychoeducation on depression<br>* Psychoeducation on depression (50minutes once a week for 4 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vagal function | Vagal function measured by 24-hr ECG (logRSA, SDNN) | at study entry, after 7 days, after 4 weeks and after 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of C-reactive protein (CRP) | CRP will be measured from serum samples at the Institute of laboratory diagnostics (Cobas analyzer) | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Interleukine-6 | Interleukine-6 will be measured from serum samples at the Institute of laboratory diagnostics | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Oxytocin | measured from serum samples with ELISA | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change of Gut microbiome | 16S sequencing of a stool sample, gut microbiome data will be analyzed with QIIME2 with regard to diversity metrices (alpha-diversity, beta-diversity) and differential bacterial abundance. | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change of Body mass Index | Weight will be measured with a calibrated scale, height will be measured with a non-expandable measuring tape. BMI will be calculated according to the formula [kg/m2]. | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Hamilton Scale for Depression (HAMD) | Scale to rate severity of depressive symptoms; 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 | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Beck Depression Inventory (BDI) | Self-rated scale to rate severity of depressive symptoms; Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depression. | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Pittsburgh Sleep Quality Inventory (PSQI) | Questionnaire to assess sleep quality; global PSQI score is calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in Adult Attachment Scale | Questionnaire to assess attachment style in adults; 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 Mediterranean Diet Score | Questionnaire rating the diet according to Mediterranean dietary style; three categories of adherence to the Mediterranean diet can be calculated (≤5, 6-9 and ≥10 points of the 14-item questionnaire) | at study entry, after 7 days, after 4 weeks and after 3 months | 
| Change in International Physical Acitivity Questionnaire | Questionnaire to rate physical activity; Physical activity is given in MET-minutes (METs are multiples of the resting metabolic rate) | 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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nutrition, mediterranean diet, vagal function, heart rate variability