End of average. understanding overweight and obesity: rationale, protocol and design of a cross-sectional and randomized controlled trial investigating predictors of effectiveness of a lifestyle intervention in adults with overweight and obesity

Obesity is globally recognized as a complex, multifactorial chronic disease, with biological, psychological, environmental and behavioural factors involved in both disease pathogenesis and maintenance. Although previous group-based studies demonstrated involvement of each of these factors, there is large inter-individual variability in the factors contributing to disease development as well as intervention outcomes, causing limited translatability to the individual level. This heterogeneity in treatment effectiveness might be due to differential causal and maintenance factors of obesity. To enable the transition from a one-size-fits-all approach to a more personalized approach for individuals with overweight or obesity, this study aims to investigate if and how the degree of weight loss and changes in daily life behaviour after a combined lifestyle intervention depend on individual baseline profiles comprising of person characteristics, biological, psychological, environmental and behavioural factors. This study will include 600 individuals varying in BMI, 200 participants with a healthy BMI (18.5–24.9 kg/m 2 ), 200 with overweight (BMI 25.0–29.9 kg/m 2 ) and 200 with obesity (BMI ≥ 30.0 kg/m 2 ). For all participants, a comprehensive individual baseline profile is created, including person characteristics, biological, psychological, environmental and behavioural factors. A clustering method is applied to identify clusters of participants with similar characteristics. Next, we examine if and how these clusters are linked to body weight indicators measured at baseline, and how they relate to daily lifestyle behaviour, as measured by ecological momentary assessment (EMA) using a smartphone app and sensor technology (3-week measurements). Individuals with overweight or obesity will be randomized to the intensive lifestyle intervention or a lifestyle information condition, to determine if treatment response can be predicted based on cluster characteristics, how daily lifestyle behaviour changes after an intervention, and how changes in daily lifestyle behaviour relate to treatment response. The End of Average study aims to characterize a large set of individuals varying in body weight to predict intervention effectiveness measured as changes in body weight indicators and in daily lifestyle behaviours. If reliable predictors of treatment success can be identified, these can be applied in personalized lifestyle interventions to improve lifestyle behaviour, body weight management and overall health. This study was registered on Research with Human Participants (CCMO)/Overview of medical research in the Netherlands under the reference NL-OMON53868 on August 21st, 2023. ( https://www.onderzoekmetmensen.nl/nl/trial/53868 ).