ESAN II - Energy Sensing in Depression

NCT05432362 | Recruiting

• 1 other identifier: ESANII
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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 immune system 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.

Conditions

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

Keywords

polyphenols; Aronia melanocarpa; immunomodulation; plant based food; natural food

Outcome Measures

Primary Outcomes (2)

• 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 Tregs 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 Outcomes (2)

• Change of baseline gut microbiome at 6 weeks (after the intervention)

  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)

  Determination at baseline and after 12 weeks (after the 6-weeks intervention and another 6 weeks of wash out)

Other Outcomes (2)

• Change of baseline metabolome at 6 weeks (after the intervention)

  Determination at baseline (day 0) and after 6 weeks (after the intervention)

• 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)

Study Arms (6)

Verum Normal Weight

EXPERIMENTAL

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

Verum Obesity

EXPERIMENTAL

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

Verum Depression

EXPERIMENTAL

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

Placebo Normal Weight

PLACEBO COMPARATOR

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

Placebo Obesity

PLACEBO COMPARATOR

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

Placebo Depression

PLACEBO COMPARATOR

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

Interventions

Aronia Juice OTHER

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 available juice in addition to their regular diet. Further, they are asked not to change their diets and lifestyle behaviour during the intervention.

Verum Depression; Verum Normal Weight; Verum Obesity

Placebo OTHER

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 Depression; Placebo Normal Weight; Placebo Obesity

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical Universtiy of Graz

Graz, Styria, 8010, Austria

RECRUITING

Related Publications (16)

• Meyrel M, Varin L, Detaint B, Mouaffak F. [The intestinal microbiota: A new player in depression?]. Encephale. 2018 Feb;44(1):67-74. doi: 10.1016/j.encep.2017.03.005. Epub 2017 Apr 24. French.

  PMID: 28438331 BACKGROUND

• Koopman M, El Aidy S; MIDtrauma consortium. Depressed gut? The microbiota-diet-inflammation trialogue in depression. Curr Opin Psychiatry. 2017 Sep;30(5):369-377. doi: 10.1097/YCO.0000000000000350.

  PMID: 28654462 BACKGROUND

• De Rosa V, Galgani M, Santopaolo M, Colamatteo A, Laccetti R, Matarese G. Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function. Semin Immunol. 2015 Sep;27(5):300-9. doi: 10.1016/j.smim.2015.10.001. Epub 2015 Oct 29.

  PMID: 26527507 BACKGROUND

• Abella V, Scotece M, Conde J, Pino J, Gonzalez-Gay MA, Gomez-Reino JJ, Mera A, Lago F, Gomez R, Gualillo O. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol. 2017 Feb;13(2):100-109. doi: 10.1038/nrrheum.2016.209. Epub 2017 Jan 5.

  PMID: 28053336 BACKGROUND

• Perez-Perez A, Vilarino-Garcia T, Fernandez-Riejos P, Martin-Gonzalez J, Segura-Egea JJ, Sanchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017 Jun;35:71-84. doi: 10.1016/j.cytogfr.2017.03.001. Epub 2017 Mar 4.

  PMID: 28285098 BACKGROUND

• Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006 May 11;441(7090):235-8. doi: 10.1038/nature04753. Epub 2006 Apr 30.

  PMID: 16648838 BACKGROUND

• Kim W, Lee H. Advances in nutritional research on regulatory T-cells. Nutrients. 2013 Oct 28;5(11):4305-15. doi: 10.3390/nu5114305.

  PMID: 24169507 BACKGROUND

• Kim YS, Sayers TJ, Colburn NH, Milner JA, Young HA. Impact of dietary components on NK and Treg cell function for cancer prevention. Mol Carcinog. 2015 Sep;54(9):669-78. doi: 10.1002/mc.22301. Epub 2015 Apr 1.

  PMID: 25845339 BACKGROUND

• Xue Z, Li D, Yu W, Zhang Q, Hou X, He Y, Kou X. Mechanisms and therapeutic prospects of polyphenols as modulators of the aryl hydrocarbon receptor. Food Funct. 2017 Apr 19;8(4):1414-1437. doi: 10.1039/c6fo01810f.

  PMID: 28287659 BACKGROUND

• Shanahan F, van Sinderen D, O'Toole PW, Stanton C. Feeding the microbiota: transducer of nutrient signals for the host. Gut. 2017 Sep;66(9):1709-1717. doi: 10.1136/gutjnl-2017-313872. Epub 2017 Jun 29.

  PMID: 28663354 BACKGROUND

• Vauzour D, Rodriguez-Mateos A, Corona G, Oruna-Concha MJ, Spencer JP. Polyphenols and human health: prevention of disease and mechanisms of action. Nutrients. 2010 Nov;2(11):1106-31. doi: 10.3390/nu2111106. Epub 2010 Nov 8.

  PMID: 22254000 BACKGROUND

• Mullan A, Delles C, Ferrell W, Mullen W, Edwards CA, McColl JH, Roberts SA, Lean ME, Sattar N. Effects of a beverage rich in (poly)phenols on established and novel risk markers for vascular disease in medically uncomplicated overweight or obese subjects: A four week randomized placebo-controlled trial. Atherosclerosis. 2016 Mar;246:169-76. doi: 10.1016/j.atherosclerosis.2016.01.004. Epub 2016 Jan 6.

  PMID: 26797134 BACKGROUND

• Aguirre L, Fernandez-Quintela A, Arias N, Portillo MP. Resveratrol: anti-obesity mechanisms of action. Molecules. 2014 Nov 14;19(11):18632-55. doi: 10.3390/molecules191118632.

  PMID: 25405284 BACKGROUND

• Chrubasik C, Li G, Chrubasik S. The clinical effectiveness of chokeberry: a systematic review. Phytother Res. 2010 Aug;24(8):1107-14. doi: 10.1002/ptr.3226.

  PMID: 20572194 BACKGROUND

• Morkl S, Lackner S, Muller W, Gorkiewicz G, Kashofer K, Oberascher A, Painold A, Holl A, Holzer P, Meinitzer A, Mangge H, Holasek S. Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls. Int J Eat Disord. 2017 Dec;50(12):1421-1431. doi: 10.1002/eat.22801. Epub 2017 Nov 13.

  PMID: 29131365 RESULT

• Lackner S, Mahnert A, Moissl-Eichinger C, Madl T, Habisch H, Meier-Allard N, Kumpitsch C, Lahousen T, Kohlhammer-Dohr A, Morkl S, Strobl H, Holasek S. Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes-secondary analysis of a randomized placebo-controlled parallel intervention trial. Microbiome. 2024 Mar 9;12(1):49. doi: 10.1186/s40168-024-01774-4.

  PMID: 38461313 DERIVED

MeSH Terms

Conditions

Depression; Obesity; Communicable Diseases

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections; Disease Attributes; Pathologic Processes

Study Officials

• Sandra Holasek, Prof.

  Medical Universtiy of Graz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sonja Lackner, Dr.

CONTACT

+43 316 385 711 66; sonja.lackner@medunigraz.at

Sandra Holasek, Prof.

CONTACT

+43 316 385 71153; sandra.holasek@medunigraz.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 27, 2022
• Study Start: February 25, 2019
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: November 27, 2024

Record last verified: 2024-11

Locations

AU (1)