Immunometabolic Effects of Non-drug Strategies in the Clinical Management of Obesity: Translational Study (PPAR-NAPAS)

Fauqué

Status: Completed

Conditions: Obesity, Abdominal; Female; Obesity, Visceral; Obesity

Treatments: Dietary Supplement: Alpha lipoic acid (plus full hospitalization); Dietary Supplement: Placebo (full hospitalization: dietary monitoring with an adapted physical activity program)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04436419

3573-I

Details and patient eligibility

About

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).

Full 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.

Enrollment: 40 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

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

ALA

Active Comparator group

Description:

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.

Treatment:

Dietary Supplement: Alpha lipoic acid (plus full hospitalization)