Immunometabolic Effects of Non-drug Strategies in the Clinical Management of Obesity: Translational Study

NCT04436419 | Completed

• 1 other identifier: 3573-I
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Forty women aged between 18 and 75 years-old with a BMI\> 30kg/m2 are recruited to participate in the evaluation of their medical management. They participate in an 8-week protocol as part of hospital medical treatment for weight loss at the Oxford Polyclinic in Cannes (IPOCA). The effects of 2 independent variables will be studied: (1) an adapted physical activity program and (2) nutritional supplementation with R-α-Lipoic acid (2x300mg/d) versus placebo (double-blind). The volunteers are randomly assigned to the different groups: Placebo with or without exercise groups and ALA with or without exercise groups. At the start of the protocol (T0), at 4 weeks (T4) and at 8 weeks (T8), various measurements are carried out (physical capacities, nutritional status, body composition, distribution of adipose mass by CT-scan). A venous sample taken for all participants is done at T0, T4 and T8 to investigate the immune profile of circulating T lymphocytes. This project is part of a translational research project to assess current care and to investigate the immunometabolic effects of a non-drug medical care of obesity (adapted physical activities, nutritional supplementation with α-lipoic acid, quality of food intake).

Conditions

Obesity; Obesity, Abdominal; Obesity, Visceral; Female

Keywords

Regulatory T cells; Immunometabolic; Alpha lipoic acid; Physical activity; Non-drug strategy; Obesity

Outcome Measures

Primary Outcomes (3)

• Variation in the prevalence of regulatory T cells from Peripheral Blood Mononuclear Cells (PBMCs) drawn from whole blood at the beginning (T0), mid-course (T4) and the end of the course (T8).

  Cells were gently washed twice and resuspended in PBS. Stained cell preparations were analyzed using a BD FACS Canto II flow cytometer. The staining and gating strategy were used for traited human PBMCs by utilizing CD3+, CD4+, CD25+ and FoxP3+ antibodies. We have discriminated CD3+CD4+ versus CD3+CD4-. Finally, at this stage CD25+FoxP3+ (Regulatory T cells) cells were gated as part of the CD3+CD4+ population.

  Through study completion, an average of 2 months

• 60% increasing in PPARβ/δ expression, estimated from the level of expression of its main target gene CPT1a, in human PBMC between the beginning (T0) and end of the course (T8).

  Total mRNA was extracted with Trizol reagent and the relative amount of CPT1a mRNA was calculated using the comparative ΔΔCT method after quantitative RT-PCR analysis.

  Through study completion, an average of 2 months

• Improvement of Redox status by measuring GSH/GSSH ratio in human whole blood between the beginning (T0) and end of the course (T8).

  The GSH/GSSG Assay is designed to accurately measure total, reduced and oxidized glutathione in biological samples using an enzymatic method that utilizes Ellman's Reagent (DTNB) and glutathione reductase (GR).

  Through study completion, an average of 3 months

Secondary Outcomes (1)

• Reduction of the area from visceral adipose tissue measured by computed-tomography scan between the beginning (T0) and end of the course (T8).

  Through study completion, an average of 1 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients benefited from a complete hospitalization including dietary monitoring (food intake was controlled in order to provide 30% less of their estimated daily energy expenditure) with a personalized food plan and an adapted physical activity program (5 sessions per week supervised by a graduated health physical activity coach), plus placebo administration (2x per day) apart from meal.

Dietary Supplement: Placebo (full hospitalization: dietary monitoring with an adapted physical activity program)

ALA

ACTIVE COMPARATOR

Patients benefited from a complete hospitalization including dietary monitoring with a personalized food plan and an adapted physical activity program, plus R-ALA enantiomer administration (2x300mg per day) apart from meal.

Dietary Supplement: Alpha lipoic acid (plus full hospitalization)

Interventions

Alpha lipoic acid (plus full hospitalization) DIETARY_SUPPLEMENT

Women are included in an 8-weeks randomized double-blind against placebo supplementation study with ALA (eight per group) according to the following criteria: Inclusion criteria: BMI\> 30; aged between 18 and 75 years. Non-inclusion criteria: HLA-DRB1\*04-03/06 polymorphisms; recent hospitalization (\<1 month); food supplement based on antioxidant; medicated in fibrate / telmisartan (modulator of PPARs); patients presenting an acute inflammatory state. Exclusion criteria: Pregnant and/or lactating women; not affiliated with social security; not mutual health insurance; person deprived of liberty; participation in clinical research in the last 6 months. Patients included in this clinical trial benefited from a complete hospitalization including dietary monitoring with a personalized food plan and an adapted physical activity program. α-LA (2x300mg/day of R-ALA) was administered double-blinded in the form of 2 capsules apart from meals.

ALA

Placebo (full hospitalization: dietary monitoring with an adapted physical activity program) DIETARY_SUPPLEMENT

Women are included in an 8-weeks randomized in placebo group. Patients included in this clinical trial benefited from a complete hospitalization including dietary monitoring with a personalized food plan and an adapted physical activity program. Placebo (2x300mg/day) was administered double-blinded in the form of 2 capsules apart from meals.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI\> 30; aged between 18 and 75 years

You may not qualify if:

• Pregnant and/or lactating women; not affiliated with social security; not mutual health insurance; person deprived of liberty; participation in clinical research in the last 6 months
• HLA-DRB1\*04-03/06 polymorphisms; recent hospitalization (\<1 month); food supplement based on antioxidant; medicated in fibrate/telmisartan (modulator of PPARs)

Sponsors & Collaborators

• Fauqué: lead
• Institut Polyclinique de Cannes (IPOCA): collaborator

Study Sites (1)

Policlinic of Oxford (IPOCA)

Cannes, 06400, France

Location

Related Publications (10)

• Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011 Aug 5;11(9):607-15. doi: 10.1038/nri3041.

  PMID: 21818123 BACKGROUND

• Mothe-Satney I, Murdaca J, Sibille B, Rousseau AS, Squillace R, Le Menn G, Rekima A, Larbret F, Pele J, Verhasselt V, Grimaldi PA, Neels JG. A role for Peroxisome Proliferator-Activated Receptor Beta in T cell development. Sci Rep. 2016 Sep 29;6:34317. doi: 10.1038/srep34317.

  PMID: 27680392 BACKGROUND

• Rousseau AS, Sibille B, Murdaca J, Mothe-Satney I, Grimaldi PA, Neels JG. alpha-Lipoic acid up-regulates expression of peroxisome proliferator-activated receptor beta in skeletal muscle: involvement of the JNK signaling pathway. FASEB J. 2016 Mar;30(3):1287-99. doi: 10.1096/fj.15-280453. Epub 2015 Dec 9.

  PMID: 26655383 BACKGROUND

• Le Garf S, Murdaca J, Mothe-Satney I, Sibille B, Le Menn G, Chinetti G, Neels JG, Rousseau AS. Complementary Immunometabolic Effects of Exercise and PPARbeta/delta Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice. Int J Mol Sci. 2019 Oct 19;20(20):5182. doi: 10.3390/ijms20205182.

  PMID: 31635041 BACKGROUND

• Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials. Clin Nutr. 2018 Apr;37(2):419-428. doi: 10.1016/j.clnu.2017.06.002. Epub 2017 Jun 8.

  PMID: 28629898 BACKGROUND

• Cui J, Huang D, Zheng Y. Ameliorative effects of alpha-lipoic acid on high-fat diet-induced oxidative stress and glucose uptake impairment of T cells. Free Radic Res. 2016 Oct;50(10):1106-1115. doi: 10.1080/10715762.2016.1210140. Epub 2016 Aug 4.

  PMID: 27383289 BACKGROUND

• Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K, Sandouk A, Hesse C, Castro CN, Bahre H, Tschirner SK, Gorinski N, Gohmert M, Mayer CT, Huehn J, Ponimaskin E, Abraham WR, Muller R, Lochner M, Sparwasser T. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014 Nov;20(11):1327-33. doi: 10.1038/nm.3704. Epub 2014 Oct 5.

  PMID: 25282359 BACKGROUND

• Kempkes RWM, Joosten I, Koenen HJPM, He X. Metabolic Pathways Involved in Regulatory T Cell Functionality. Front Immunol. 2019 Dec 3;10:2839. doi: 10.3389/fimmu.2019.02839. eCollection 2019.

  PMID: 31849995 BACKGROUND

• Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol. 2016 May 19;17(6):618-25. doi: 10.1038/ni.3466.

  PMID: 27196520 BACKGROUND

• Zou J, Lai B, Zheng M, Chen Q, Jiang S, Song A, Huang Z, Shi P, Tu X, Wang D, Lu L, Lin Z, Gao X. CD4+ T cells memorize obesity and promote weight regain. Cell Mol Immunol. 2018 Jun;15(6):630-639. doi: 10.1038/cmi.2017.36. Epub 2017 Jun 19.

  PMID: 28626237 BACKGROUND

MeSH Terms

Conditions

Obesity; Obesity, Abdominal; Motor Activity

Interventions

Thioctic Acid

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 18, 2020
• Study Start: July 2, 2018
• Primary Completion: February 28, 2020
• Study Completion: March 16, 2020
• Last Updated: June 24, 2020

Record last verified: 2020-06

Locations

FR (1)