ESAN II - Energy Sensing in Depression

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of polyphenols from natural aronia juice on the immune system. Therefore, the study aims to distinguish the effects of natural juices that are rich in phytonutrients such as polyphenols and carotenoids in healthy and depressive subjects in order to use the known positive effects of these food sources in the therapeutic setting. The consumption of natural fruit juices that are rich in polyphenols and carotenoids mirror a model of vegetarian diet due to the increased micronutrient density derived from plant food. Results obtained here can be seen as preliminary explanation models for the beneficial effects of vegetarian diet. It is hypothesized, that the consumption of naturally polyphenol rich aronia juice changes the expression of regulatory T cells, specific cells of the immunesystem that contribute to immunomodulation. Furthermore, beneficial changes in the gut microbiome, the metabolome and the nutritional status are expected in the studied groups. The study was registered retrospectively (after start of recruitment) on Clinicaltrials.gov.

Official Title
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ESAN II - Energy Sensing in Depression. Effects of Aronia Melanocarpa on Immunomodulation in Patients With Obesity, Depression, and Normal Weight Controls.

Conditions
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Immune System Tolerance, Depression, Obesity, Microbial Colonization, Diet, Healthy

Intervention / Treatment
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* Other: Aronia Juice
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Socio-demographic criteria: Gender: female Age: 18-40 years Confirmation of the study settings receives of information on the aims, methods, anticipated benefits, potential risks, and entailed discomforts of the study signed declaration of consent Subgroup of depressive patients: diagnosis of depression according to the ICD-10 criteria for depression diagnosed by an experienced psychiatrist a structured diagnostic interview voluntarily agreement to participate signed informed consent Subgroup of normal weight participants: WHO criteria for normal weight (body mass index (BMI) 18.5-24.99 kg/m2) Subgroup of obese participants WHO criteria for obesity (BMI < 30.0 kg/m2) Exclusion Criteria: Formal criteria: lack of informed consent Health criteria alcohol- or drug abuse major cognitive deficits (which do not allow adequate testing) according to Mini Mental Status Examination (MMSE) <20 patients which are currently in the locked ward of the clinic acute or chronic diseases or infections within the previous two months upper respiratory tract infections fever chronic inflammatory disorders autoimmune-disorders blood diseases mitochondrial diseases Digestive disorders fructose intolerance history of digestive diseases such as inflammatory bowel disease irritable bowel syndrome treatment that may has influenced the microbiome antibiotic or antifungal treatment within the previous two months daily or irregular intake of prebiotics or probiotics within the previous two months (the intake of yoghurt and dairy products are permitted) history of gastrointestinal surgery (other than appendectomy) Pregnancy and period of breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This monocentric study is a food product study (comparison between in trade available polyphenol-rich juice and a placebo). Aronia juice is a locally produced, commercially available natural source of various secondary plant nutrients. It naturally contains high amounts of polyphenols. The placebo juice is prepared according to a published recipe and contains comparable amounts of nutrients such as vitamins and minerals but is totally polyphenol-free. Six study groups are designated: Group VN = normal weight participants receiving polyphenol-rich juice (verum) (n=20) Group VA = adipose participants receiving polyphenol-rich juice (verum) (n=20) Group VD = depressive patients receiving polyphenol-rich juice (verum) (n=20) Group CN = normal weight participants receiving placebo (control) (n=20) Group CA = adipose participants receiving placebo (control) (n=20) Group CD = depressive patients receiving placebo (control) (n=20)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum Normal Weight<br>Normal weight participants receiving polyphenol-rich Aronia juice (verum) (n=20) The aronia juice is derived from a local producer, a common food and commercially available. | Other: Aronia Juice<br>* The intervention is based an the additional consumption of 200 ml natural juice a day for a period of six weeks. The participants are asked to drink the natural and commercially availabe juice in addition to their regular diet. Further, they are asked not to change their diets and lifestyle behaviour during the intervention.<br>|
| Experimental: Verum Obesity<br>Adipose participants receiving polyphenol-rich Aronia juice (verum) (n=20) The aronia juice is derived from a local producer, a common food and commercially available. | Other: Aronia Juice<br>* The intervention is based an the additional consumption of 200 ml natural juice a day for a period of six weeks. The participants are asked to drink the natural and commercially availabe juice in addition to their regular diet. Further, they are asked not to change their diets and lifestyle behaviour during the intervention.<br>|
| Experimental: Verum Depression<br>Depressive participants receiving polyphenol-rich Aronia juice (verum) (n=20) The aronia juice is derived from a local producer, a common food and commercially available. | Other: Aronia Juice<br>* The intervention is based an the additional consumption of 200 ml natural juice a day for a period of six weeks. The participants are asked to drink the natural and commercially availabe juice in addition to their regular diet. Further, they are asked not to change their diets and lifestyle behaviour during the intervention.<br>|
| Placebo Comparator: Placebo Normal Weight<br>Normal weight participants receiving placebo (control) (n=20) The placebo drink is prepared according to a published recipe and contains nutrients such as sugars, vitamins and minerals. It has a comparable nutrients profile as the aronia juice but is completely polyphenol-free. | Other: Placebo<br>* A beverage is prepared according to a known recipe. It contains macro- and micronutrients in comparable amounts like the aronia juice. It is completely polyphenol free.<br>|
| Placebo Comparator: Placebo Obesity<br>Obese participants receiving placebo (control) (n=20) The placebo drink is prepared according to a published recipe and contains nutrients such as sugars, vitamins and minerals. It has a comparable nutrients profile as the aronia juice but is completely polyphenol-free | Other: Placebo<br>* A beverage is prepared according to a known recipe. It contains macro- and micronutrients in comparable amounts like the aronia juice. It is completely polyphenol free.<br>|
| Placebo Comparator: Placebo Depression<br>Depressive participants receiving placebo (control) (n=20) The placebo drink is prepared according to a published recipe and contains nutrients such as sugars, vitamins and minerals. It has a comparable nutrients profile as the aronia juice but is completely polyphenol-free | Other: Placebo<br>* A beverage is prepared according to a known recipe. It contains macro- and micronutrients in comparable amounts like the aronia juice. It is completely polyphenol free.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of baseline regulatory T cells (Tregs) at 6 weeks (after the intervention) | Tregs are involved in modulating the immune system and maintaining tolerance to self-antigens and preventing autoimmune diseases. Regulatory T cells (Treg) will be quantified using multiparameter flow cytometry. Monoclonal antibodies specific for surface markers such as CD3, CD4, CD45RA, CD39 and CD25 will be combined with intracellular anti-Foxp3 for the identification of human Treg. | Determination at baseline (day 0) and after 6 weeks (after the intervention) | 
| Change of baseline regulatory T cells (Tregs) at 12 weeks (after the intervention and another 6 weeks of wash out) | Tregs are involved in modulating the immune system and maintaining tolerance to self-antigens and preventing autoimmune diseases. The assessment of Trges after 12 weeks aims to identify any persisting effects of the intervention. | Determination at baseline and after 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of baseline gut microbiome at 6 weeks (after the intervention) | Stool samples will be collected with the PSP spin stool DNA stool collection kit (Stratec, Birkenfeld, GER) and processed according to the suppliers recommendations. Subsequently to DNA extraction the variable V1-V2 region of the bacterial 16S rRNA gene is amplified with PCR using oligonucleotide primers BSF8 and BSR357. | Determination at baseline (day 0) and after 6 weeks (after the intervention) | 
| Change of baseline gut microbiome at 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out) | Stool samples will be collected with the PSP spin stool DNA stool collection kit (Stratec, Birkenfeld, GER) and processed according to the suppliers recommendations. Subsequently to DNA extraction the variable V1-V2 region of the bacterial 16S rRNA gene is amplified with PCR using oligonucleotide primers BSF8 and BSR357. The assessment of the change in the gut microbiome after 12 weeks aims to identify any persisting effects of the intervention. | Determination at baseline and after 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polyphenols, Aronia melanocarpa, immunomodulation, plant based food, natural food