Protocol for a randomised, double-blinded, controlled trial of youth with childhood-onset obesity treated with semaglutide 2.4 mg/week: the RESETTLE trial

Abstract

Introduction: Childhood-onset obesity poses significant health risks, including early-onset type 2 diabetes, cardiovascular disease, and reduced quality of life. Hospital-based non-pharmacological obesity care can reduce childhood obesity, but 25% of children do not respond. Therefore, this study investigates the effect of the glucagon-like peptide-1 receptor agonist, semaglutide, as an add-on to hospital-based obesity care in youth who still have obesity following hospital-based obesity care as children. Furthermore, biomedical and psychosocial factors linked to treatment response will be investigated, alongside an exercise-based strategy to prevent weight regain and maintain a healthy body composition after semaglutide treatment.

Methods and analysis: This is an investigator-initiated, randomised, placebo-controlled, double-blind trial. We will enrol expectedly 180-270 young adults aged 18-28 years based on their previous response to a paediatric obesity management programme and their current body mass index (BMI). Participants are categorised into four groups: low treatment response (BMI SD score (SDS) reduction <0.10; BMI ≥30 kg/m²); medium treatment response (BMI SDS reduction >0.25; BMI ≥30 kg/m²); high treatment response (BMI SDS reduction >0.50; BMI <30 kg/m²) and a population-based reference group with normal weight development in childhood. Participants with BMI ≥30 kg/m² are randomised 2:1 to subcutaneous injections of semaglutide 2.4 mg/week or placebo as an add-on to hospital-based obesity care for 68 weeks. The primary outcome is the change in BMI from randomisation to the end of treatment with semaglutide compared with placebo. Secondary endpoints are changes in weight and body composition.

Ethics and dissemination: The trial has been approved by the Danish Medicines Agency and the Ethical Committee of the Capital Region of Denmark (H-20039422). The trial will be conducted in accordance with the Declaration of Helsinki and follow the guidelines for Good Clinical Practice. Results will be presented at international scientific conferences and published in peer-reviewed scientific journals.

Trial registration number: EudraCT 2019-002274-31.

Keywords: Body Mass Index; Obesity; Randomized Controlled Trial.

Figure 1. Study design.