Alstrom Syndrome, Bardet Biedl Syndrome, Bardet Biedl Syndrome (BBS), Bardet-Biedl Syndrome (BBS)
Conditions
Keywords
Setmelanotide, Melanocortin-4-receptor, Melanocortin pathway, Bardet-Biedl Syndrome, Hyperphagia, Neurocognitive development, Genetic Obesity
Brief summary
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.
Detailed description
The MC4R signaling pathway is a key regulator of appetite and energy balance. Genetic defects affecting this pathway lead to severe obesity syndromes including Bardet-Biedl syndrome and other rare monogenic obesity disorders. Although pivotal clinical trials demonstrated efficacy of Setmelanotide, evidence from routine clinical care remains limited. This study seeks to characterize treatment outcomes in everyday clinical practice, including changes in body weight, BMI, hyperphagia, metabolic parameters, quality of life, treatment adherence, and adverse events. Patients receiving approved MC4R agonist therapy will be followed prospectively. Data will be collected during routine outpatient visits and include anthropometric, clinical, laboratory, and patient-reported measures. The study infrastructure is intended to serve as a platform for future MC4R agonists approved for severe genetic obesity disorders.
Interventions
DRUGSetmelanotide
Administration according to approved product labeling and treating physician discretion
Sponsors
Tom Hühne
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective real-world observational interventional cohort of patients receiving approved MC4 receptor agonist therapy in routine clinical care.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* clinical phenotype corresponding to Bardet-Biedl Syndrome * genetic testing with notable finding
Exclusion criteria
* patients younger than the age approved for treatment with setmelanotide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in BMI z-score | Baseline to 12/24/36/48/60/72 months | Relative change in BMI z-Score after initiation of MC4 receptor agonist therapy |
| Impact on lipid profile | Baseline to 12/24/36/48/60/72 months | Changes in lipid profile measured by cholesterol blood levels |
| Change in Hepatic Fat Attenuation | Baseline to 12/24/36/48/60/72 months | Hepatic Fat Attenuation will be measured by ultrasound Attenuation imaging across different time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Life quality | Baseline to 12/24/36/48/60/72 months | 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 | Baseline to 12/24/36/48/60/72 months | Incidence of adverse events, serious adverse events and treatment discontinuations and reasons for it |
| Cognitive changes | Baseline to 12/24/36/48/60/72 months | 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 | Baseline to 12/24/36/48/60/72 months | 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. |
| Changes on hypothalamic-pituitary-gonadal axis | Baseline to 12/24/36/48/60/72 months | Hypothalamic-pituitary-gonadal axis is investigated by longitudinal measurements of testosterone and estradiol levels in blood. |
Countries
Germany
Contacts
CONTACTTom Hühne, Dr. med.
CONTACTLars Dinkelbach, Dr. med.
PRINCIPAL_INVESTIGATORMetin Cetiner, PD Dr. med.
Universitätsmedizin Essen
Outcome results
None listed