ESAN II - Energy Sensing in Depression

Sponsor

Medical University of Graz (Other)

Overall Status

Recruiting

CT.gov ID

NCT05432362

Collaborator

(none)

120

Enrollment

Location

Arms

47.2

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Immune System Tolerance Depression Obesity Microbial Colonization Diet, Healthy	Other: Aronia Juice Other: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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)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 (Participant)

Masking Description:

The randomizer (online tool of the Medical University of Graz) will be used for randomisation of group assignment. The two juices are provided in the same containers.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 25, 2019

Anticipated Primary Completion Date :

Jan 31, 2023

Anticipated Study Completion Date :

Jan 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Verum Normal Weight 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 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.
Experimental: Verum Obesity 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 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.
Experimental: Verum Depression 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 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.
Placebo Comparator: Placebo Normal Weight 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 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.
Placebo Comparator: Placebo Obesity 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 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.
Placebo Comparator: Placebo Depression 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 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.

Outcome Measures

Primary Outcome Measures

Change of baseline regulatory T cells (Tregs) at 6 weeks (after the intervention) [Determination at baseline (day 0) and after 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.
Change of baseline regulatory T cells (Tregs) at 12 weeks (after the intervention and another 6 weeks of wash out) [Determination at baseline and after 12 weeks (after the 6-weeks 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.

Secondary Outcome Measures

Change of baseline gut microbiome at 6 weeks (after the intervention) [Determination at baseline (day 0) and after 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.
Change of baseline gut microbiome at 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out) [Determination at baseline and after 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.

Other Outcome Measures

Change of baseline metabolome at 6 weeks (after the intervention) [Determination at baseline (day 0) and after 6 weeks (after the intervention)]
The metabolome can be identified in various biological materials such as blood (EDTA and serum) Metabolites in blood will be analyzed by using 1H-NMR spectra. A non-targeted approach will be applied to characterize a potential shift in the participants' metabolic profile.
Change of baseline metabolome at 12 weeks (after the 6 weeks intervention and another 6 weeks of wash out) [Determination at baseline and after 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out)]
The metabolome can be identified in various biological materials such as blood (EDTA and serum) Metabolites in blood will be analyzed by using 1H-NMR spectra. A non-targeted approach will be applied to characterize a potential shift in the participants' metabolic profile.The assessment of the change in the metabolome after 12 weeks aims to identify any persisting effects of the intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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)