Clinical trials

Among the new strategies being considered for the treatment of obesity and its metabolic complications, the activation of brown adipose tissue (BAT) from white adipose tissue looks promising. Interest in the study of BAT has increased over the last 5-10 years in response to the discovery of functional BAT in humans. The BAT is a tissue specialized in regulating energy expenditure by producing heat through the oxidation of fatty acids contained in the multiple lipid droplets of brown adipocytes. This adipose tissue does not play a storage role, but rather an anti-obesogenic one, thanks to its high metabolic and energetic activity. In addition to exposure to cold, which is the major physiological inducer of brown adipocytes, it seems that exercise and the intake of "adrenergic" foods can activate the TAB and potentially induce a change from white to brown tissue via the production of adrenalin and myokines. Acute and/or chronic effects of thermogenic food supplements have been reported on BAT activation and energy metabolism. The most conclusive of these involve the capsinoids found in sweet peppers and chillies. Weight loss also improves BAT activation. The BAT has already been identified in children. A decrease in its volume and activity from childhood to adolescence and during puberty has been reported. The main objective of this randomized controlled double-blind study is to investigate the effects of capsinoid dietary supplementation on BAT activity in obese adolescents. Our general working hypothesis is that capsinoid supplementation, combined with dietary management, leads to an increase in BAT activity.

The management of a person with obesity involves long-term behavioral changes with a balanced diet in both quantity and quality, along with the adoption of a more active lifestyle: increasing physical activities and reducing sedentary behaviors. The school setting has been identified as a favorable environment for interventions aimed at reducing and interrupting the time adolescents spend sitting and preventing the associated negative health consequences. Recently, very short (\< 1 minute) and intense exercises, called 'exercise-snacks,' have been reported to be effective in adults for 1) improving physical fitness over 6 weeks, and 2) improving vascular function and lowering blood glucose levels over a single day. Additionally, in adolescents with diabetes, they have been shown to reduce body fat. This raises the question of whether adding \'exercise-snack\' sessions to a multidimensional care program for hospitalized obese adolescents could further improve their physical fitness in the short and medium term. The objective of this project is to compare the effects of a traditional multidimensional care program with the addition of 'exercise-snacks' to the same care program without \'exercise-snacks\' on the physical fitness, body composition, vascular function, and physical activity and sedentary behaviors of obese children in the short and medium term. Forty-eight obese adolescents will be included. The \'exercise-snack\' group will perform six exercise sessions per day for three weeks in addition to the standard care. The control group will receive only the standard care. Assessments of physical fitness, body composition, vascular health, and questionnaires on physical activity, sedentary behavior, and cognitive restraint will be conducted at the beginning and end of the three-week program, as well as 1 and 3 months after the end of the program.

Exercise-induced cardiac remodeling, known as the "athlete's heart," corresponds to morphological and functional adaptations of the left ventricle in response to prolonged physical training. It is characterized in particular by physiological hypertrophy and improved myocardial function. Intraventricular blood flow interacts with cardiac mechanics. Regional shape (e.g., sphericity, wall curvature) and myocardial deformations guide flow patterns to create an optimal hemodynamic environment. The interaction between these different parameters in the athlete's heart remains insufficiently explored. In this context, 3D echocardiography makes it possible to combine indices derived from fluid dynamics, regional myocardial function, and cardiac geometry, enabling a comprehensive assessment of cardiac performance. Primary and secondary objectives: In this context, the aim of this project is to investigate the relationship between intraventricular flow and cardiac mechanics based on combined measurements of intraventricular flow (e.g., vorticity, pressure gradients), regional myocardial function (e.g., myocardial strain), and global/regional LV geometry (e.g., sphericity, wall curvature) in the athlete's heart. Since these parameters are interdependent, analyzing their interaction through the development of new echocardiographic tools based on 4D assessments will enable a comprehensive evaluation of functional improvements in the athlete's heart. The secondary objectives are to analyze the impact of dyssynchrony on intraventricular flow, to evaluate the influence of primary and secondary deformations on intraventricular flow, and to study cardiac function from an energetic perspective using non-invasive reconstruction of pressure-volume loops for cardiac work estimation. Methodology: The study will include 80 endurance athletes (ENT group) and 80 control subjects (CONT group). The main inclusion criteria common to both groups are: men and women aged 18-45 years, with no known heart disease and no cardiovascular risk factors (e.g., body mass index \> 30 kg/m², arterial hypertension). Athletes must train at least 10 hours per week for the past 5 years. Control subjects must not engage in more than 3 hours of physical activity per week. Athletes will be recruited from elite groups of various federations, during local long-distance races, or during clinical evaluations at Montpellier University Hospital (Dr. C. Hédon's department). Control subjects will be recruited in the Avignon area and in the cardiology department of Montpellier University Hospital during routine visits. Echocardiographic examinations will be performed in the left lateral decubitus position using Vivid systems with 4D probes. 4D and tri-plane acquisitions with color Doppler will allow assessment of cardiac structure and intraventricular flow. Data analysis will be performed using TOMTEC software, and scripts developed in Matlab and RStudio will process information related to shape, mechanical dispersion, and dyssynchrony. Intraventricular hemodynamics will be analyzed in collaboration with the CREATIS laboratory (D. Garcia), particularly through measurements of intraventricular pressure gradients and vorticity indices.

The main objective is to evaluate in hemodialysis patients the effects of two intradialytic rehabilitation programs based on physical exercise, with or without the application of blood flow restriction, on myocardial stunning and morpho-functional cardiac remodelling, compared with usual care (i.e., dialysis without exercise). In addition, the investigators will also assess the acute effects (i.e., a single session for each condition) of physical exercise, with or without blood flow restriction, on myocardial stunning at the end of dialysis. In comparison with a conventional exercise program, the combination of physical exercise with blood flow restriction, which synergistically and additively activates intramuscular signalling pathways related to both exercise and ischaemia, is hypothesised to result in: 1. A greater intradialytic cardioprotection, as demonstrated by a greater reduction in myocardial stunning at the end of dialysis (both in acute and chronic applications), with underlying mechanisms involving systemic and neuro-humoral pathways; 2. Significant improvements in morpho-functional cardiac remodelling, attenuation of arrhythmic disturbances, and enhancement of aerobic capacity, muscle strength, and muscle mass-effects not observed with exercise alone without blood flow restriction, considering the low exercise intensity used in the current rehabilitation program (chronic application only). This is a three-arm randomised clinical trial with parallel groups: standard hemodialysis (HD-CONTChro), a rehabilitation program with intradialytic exercise without vascular occlusion (HD-EXChro), and a rehabilitation program with intradialytic exercise with vascular occlusion (HD-BFREChro), with a 1:1:1 allocation ratio. To investigate the acute effects of the interventions, all patients will undergo, in a randomized order, one session of each of the three dialysis modalities-standard hemodialysis (HD-CONTacute), hemodialysis with exercise without vascular restriction (HD-EXacute), and hemodialysis with exercise with vascular restriction (HD-BFREacute)-prior to initiation of the chronic phase of the study.