Clinical trial NCT04436419: Immunometabolic Effects of Non-drug Strategies in the Clinical Management of Obesity: Translational Study
Official title: Immunometabolic Effects of Non-drug Strategies in the Clinical Management of Obesity: Translational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Obesity, Abdominal
Obesity, Visceral
Female
Keywords: Regulatory T cells
Immunometabolic
Alpha lipoic acid
Physical activity
Non-drug strategy
Obesity
Lead sponsor: Institut Polyclinique de Cannes (IPOCA)
Sponsor class: INDUSTRY
Collaborators: name: Institut Polyclinique de Cannes (IPOCA)
First posted: 2020-06-18
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Detailed description: Obesity-related inflammation is central to the development of type 2 diabetes and potentiated by advancing age, inactive behavior and sedentary lifestyle. Metabolism and immunity are entangled in their respective effects: the pathways of inflammation are involved in metabolism and the metabolic state plays a predominant role in immune function. Physical activity and calorie restriction are first-line, non-drug strategies recommended in reducing obesity and insulin resistance and then prevent type 2 diabetes. However, the impact of their combined effects on circulating immune cells or those residing in adipose tissue and skeletal muscle, remains insufficiently understood to allow a nutritional prescription (i.e., quality of nutritional intake and efficient doses of physical activity) favorable to preventive medical care, individualized, and effective. If the risk associated with an increase in visceral fat mass is linked to a change in the pro/anti-inflammatory status, it is essential to reduce this risk by acting on its cause, regardless of the weight loss. In a context of low-grade inflammation, these effects could lead to an anti-inflammatory profile of T cells, specifically regulatory T cells (Treg) whose metabolism is extremely "flexible" at the periphery and into visceral adipose tissue (directly involved in inflammation of obesity).

ALA (Alpha-Lipoic Acid) is known to play a pivotal role in cellular redox status and energy metabolism by modulating inflammatory and metabolic signaling pathways such as those of NF-kB, JNK, PI3K/Akt, p38 MAPK, AMPK or PPARβ/δ. As ALA is a possible metabolic modulator, it would affect the metabolism of T cells. And therefore ALA could be a complementary measure to non-drug strategies by potentiating the correction of the inflammatory state linked to obesity.

Eligibility criteria: Inclusion Criteria:

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

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

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)

Primary outcomes:
measure: 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).
timeFrame: Through study completion, an average of 2 months
measure: 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).
timeFrame: Through study completion, an average of 2 months
measure: Improvement of Redox status by measuring GSH/GSSH ratio in human whole blood between the beginning (T0) and end of the course (T8).
timeFrame: Through study completion, an average of 3 months
Secondary outcomes:
measure: Reduction of the area from visceral adipose tissue measured by computed-tomography scan between the beginning (T0) and end of the course (T8).
timeFrame: Through study completion, an average of 1 months
Other outcomes:
Locations:
city: Cannes
country: France
facility: Policlinic of Oxford (IPOCA)
Study officials:
References:
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