Bardet-Biedl syndrome (BBS) and other rare disorders associated with impairment of the melanocortin-4 receptor (MC4R) pathway are characterized by severe early-onset obesity, hyperphagia, and substantial morbidity. Setmelanotide, an MC4R agonist, is approved in Europe for selected genetic obesity disorders and reimbursed in Germany for eligible patients. This study aims to evaluate the effectiveness, safety, treatment persistence, metabolic outcomes, and patient-reported outcomes of Setmelanotide under real-world conditions. The registry is designed to allow future inclusion of additional MC4R agonists as they become approved and clinically available. The study will primarily be conducted at University Hospital Essen and will collect longitudinal routine clinical data from pediatric and adult patients receiving MC4R agonist therapy according to approved indications.
clinical phenotype corresponding to Bardet-Biedl Syndrome
genetic testing with notable finding
patients younger than the age approved for treatment with setmelanotide
Single group
Setmelanotide
DrugAdministration according to approved product labeling and treating physician discretion
Percent change in BMI z-score
Relative change in BMI z-Score after initiation of MC4 receptor agonist therapy
Impact on lipid profile
Changes in lipid profile measured by cholesterol blood levels
Change in Hepatic Fat Attenuation
Hepatic Fat Attenuation will be measured by ultrasound Attenuation imaging across different time points
Life quality
Patient-reported quality of life using e.g. the "Impact of weight on Quality of life"-questionnaire (IWQOL). The assessment is based on a scale from 0 to 100, with 100 representing the best possible weight-related quality of life.
Safety and Tolerability
Incidence of adverse events, serious adverse events and treatment discontinuations and reasons for it
Cognitive changes
Neurocognitive impairment is common in Bardet-Biedl Syndrome. Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) for children and Wechsler Adult Intelligence Scale (WAIS) for adults are performed to investigate cognition before and after intervention.
Functional brain connectivity
Newly diagnosed patients undergo non-invasive functional magnetic resonance imaging (fMRI) both prior to treatment initiation and three months afterward. The scanning protocol will include structural T1-weighted MRI sequences (8 minutes), resting-state fMRI (4 runs of 5.5 minutes each; 22 minutes total), and task-based fMRI to assess responses to high- and low-fat food cues (2 runs of 5.5 minutes each; 11 minutes total). The imaging component will enable the investigation of treatment-related changes in functional brain connectivity associated with setmelanotide.
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Tom Hühne
Lead sponsor
University Hospital, Essen
Sponsor institution
Rhythm Pharmaceuticals, Inc.
Collaborator
