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NCT Number: NCT07674290

Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity

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.

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Key information

Conditions

Bardet Biedl Syndrome (BBS) Abnormalities, Multiple Alstrom Syndrome Bardet Biedl Syndrome Bardet-Biedl Syndrome Bardet-Biedl Syndrome (BBS) Brain Diseases Central Nervous System Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Hereditary Sensory and Motor Neuropathy Heredodegenerative Disorders, Nervous System Hyperphagia Hypothalamic Diseases Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Polyneuropathies Retinitis Pigmentosa Signs and Symptoms Signs and Symptoms, Digestive

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University Hospital Essen, Deparment of Pediatrics II

Essen, 45147, Germany

Location status: Recruiting

Location contact

Metin Cetiner, PD Dr. med.

CONTACT

[email protected]

+49 201 723 84722

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Setmelanotide

Drug

Administration according to approved product labeling and treating physician discretion

Primary outcomes

  1. Percent change in BMI z-score

    Time frame: Baseline to 12/24/36/48/60/72 months

    Relative change in BMI z-Score after initiation of MC4 receptor agonist therapy

  2. Impact on lipid profile

    Time frame: Baseline to 12/24/36/48/60/72 months

    Changes in lipid profile measured by cholesterol blood levels

  3. Change in Hepatic Fat Attenuation

    Time frame: Baseline to 12/24/36/48/60/72 months

    Hepatic Fat Attenuation will be measured by ultrasound Attenuation imaging across different time points

Secondary outcomes

  1. Life quality

    Time frame: 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.

  2. Safety and Tolerability

    Time frame: Baseline to 12/24/36/48/60/72 months

    Incidence of adverse events, serious adverse events and treatment discontinuations and reasons for it

  3. Cognitive changes

    Time frame: 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.

  4. Functional brain connectivity

    Time frame: 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.

  5. Changes on hypothalamic-pituitary-gonadal axis

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Lars Dinkelbach, Dr. med.

CONTACT

[email protected]

Tom Hühne, Dr. med.

CONTACT

[email protected]

+49 201 723 86211

Sponsors and collaborators

Lead sponsor

Tom Hühne

Other

Collaborators

  • Rhythm Pharmaceuticals, Inc.

Registry information

Official study title

Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome: A Prospective Mono Centric Observational Interventional Study

Acronym: REAL-MC4

Important dates

Study start
2023
Primary completion
2030
Study completion
2030
First posted
Jun 29, 2026
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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