Tracing the effect of the melanocortin-4 receptor pathway in obesity: study design and methodology of the TEMPO registry

Abstract

Ihuoma Eneli,1,2 Jinyu Xu,1 Matthew Webster,3 Amy McCagg,3 Lex Van Der Ploeg,3 Alastair S Garfield,3 Elizabeth Estrada41Center for Healthy Weight and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA; 2Department of Pediatrics, The Ohio State University, Columbus, OH, USA; 3Department of Medical Communications, Rhythm Pharmaceuticals, Inc, Boston, MA, USA; 4Department of Pediatric Endocrinology, University of North Carolina, Chapel Hill, NC, USAPurpose: The hypothalamic melanocortin-4 receptor (MC4R) pathway, a component of the central melanocortin pathway, regulates energy balance and satiety. Rare genetic disorders of obesity may be characterized by impaired MC4R pathway signaling, which results in early-onset severe obesity and insatiable hunger (hyperphagia). The TEMPO registry (NCT03479437) is a voluntary, prospective, open-ended registry of individuals with rare genetic disorders of obesity due to mutations in genes within the MC4R pathway who have early-onset severe obesity. The objective of the TEMPO registry is to evaluate the burden of rare genetic disorders of obesity on individuals, their parents/caregivers, health care providers, and the health care system.Patients and methods: Individuals with rare genetic disorders of obesity (adults aged ≥18 years and children and adolescents aged from 2 to 17 years) will be referred by their health care providers or by a genetic screening study. Individuals must meet age- and sex-specific body mass index values that define the clinical criteria for severe obesity and carry selected variants in MC4R or in one of several genes upstream or downstream of the MC4R. Online surveys will be completed by the individual, parent/caregiver, and health care provider at baseline and annually thereafter and will collect data on demographics, results of genetic testing, medical/family history, disease characteristics, resource utilization, eating habits/hunger episodes, social and emotional impacts, and interest in future clinical trial participation.Conclusions: The TEMPO registry will provide insights into the overall course and disease burden for individuals with rare genetic disorders of obesity. Health care providers may use this resource to improve the identification, diagnosis, and treatment of individuals with rare forms of genetic obesity.Keywords: Alström syndrome, Bardet-Biedl syndrome, LEPR, PCSK1, POMC, severe obesity

Keywords

• Alström syndrome
• Bardet-Biedl syndrome
• LEPR
• PCSK1
• POMC
• severe obesity