JOULE - Metabolic Adaptation to Weight Loss in Response to a Behavioural Lifestyle Program With or Without Semaglutide in Adolescents With Obesity

The Joule MARS (Metabolic Adaptation to weight loss in Response to a behavioural lifestyle program with or without Semaglutide in adolescents with obesity) study is a single-center, randomized controlled trial designed to investigate the effects of a behaviour lifestyle program and the medication semaglutide on resting energy expenditure (REE), work efficiency during standard exercise on a cycle ergometer and related metabolic outcomes in adolescents with obesity. The study will involve two intervention groups: Group A will participate in a behavioral lifestyle program (BLP) alone for 6 months followed by a combination of semaglutide treatment and a BLP for an additional 6 months. Group B will receive semaglutide and a BLP for the first 6 months and then terminate the study. The study objectives are to determine if, in youth aged 12-17 years with obesity and enrolled in a weight management program: 1. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone leads to less adaptive thermogenesis (AT) at 6 months; 2. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone for 6-month, leads to: Less increase in energy work efficiency during standardized exercise Differences in BAT activity Differences in health-related quality of life (HRQoL) 3. BLP and semaglutide, compared to BLP alone, lead to improvements in metabolic health measures (including lipids, glycemia, liver enzymes, hepatic fat and hepatic stiffness) after 6 months. 4. A longer time enrolled in BLP prior to addition of 6 months of semaglutide alters health outcome response to semaglutide. A comprehensive assessment will be conducted throughout the study. Using whole-room indirect calorimetry, REE and muscle work efficiency, evaluated during standardized physical activity on a cycle ergometer, will be measured. Body composition (Dual energy x-ray absorptiometry and bioelectric impedance analysis), anthropometry (height, weight, waist circumference, BMI, BMI z score (WHO)), metabolic health, health related quality of life, hepatic fat and cold induced brown adipose tissue activity (MRI) will be assessed. Randomization will be managed via the REDCap EDC system.