• Genetic syndromes, congenital disorders, hereditary conditions • Hormonal disorders, metabolic/endocrine dysfunction • Neurodevelopmental disorders, neurological conditions • Conditions that a person is born with or inherits from their family, such as Down syndrome or cystic fibrosis. • Problems with the body’s hormones or how it processes food and energy, like diabetes or thyroid issues. • Conditions that affect how the brain develops or works, such as autism, ADHD, or epilepsy.
Conditions
Interventions
Not applicable, this study is an observational study.
Sponsors
Amsterdam UMC
Eligibility
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: PWS patient group:Genetically confirmed diagnosis of PWS.Age 18 or older.Capable of undergoing cognitive and behaviour assessments, blood sampling, PET-CT and MRI procedures with caregiver support.A caregiver is available and willing to assist throughout the study procedures (e.g., logistics, assessments, behavioral support).Informed consent is provided by the participant or their legal representative (parents or legal guardians). Control group:Healthy individual aged older than 18 years (preferably sibling, with same sex).No history of major neurological, psychiatric, or developmental disorders.Able to undergo cognitive and behaviour assessments, blood sampling, PET-CT and MRI procedures and provide informed consent.
Exclusion criteria
Exclusion criteria: No caregiver available to assist in key study tasks for PWS participants (e.g., behavior management, proxy questionnaire completion).History of epilepsy or seizure disorders, and history of self-injury or suicidal ideation (in PWS group).Severe cardiac abnormalities or ECG abnormalities.Use of medications that strongly influence cholinergic neurotransmission and cannot be paused safely.Behavioral or cognitive limitations that preclude safe PET-CT and MRI imaging, even with caregiver support.Contraindications for MRI:Metal implants, severe claustrophobia.Body weight above 225 kg.Inability to walk up a staircase independently. Pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of this observational cohort study is the assessment of cholinergic impairment in individuals with PWS compared to the non-PWS controls. This will be measured through the following parameters:[18F]FEOBV PET imaging to quantify cholinergic activity in the brain, particularly focusing on the expression of ChAT-expressing neurons in key regions associated with cognitive function and hyperphagia.Cognitive performance measures will be assessed using a standardized neurocognitive battery to evaluate impairments in attention, memory, and executive function.Hyperphagia assessment: Measurement of food intake behaviors using validated questionnaires.These endpoints will be used to assess the extent of cholinergic dysfunction in study participants and to examine whether it correlates with cognitive and behavioral impairments, as well as hyperphagia. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints include:Plasma ACh concentrations for correlation with neuroimaging and cognitive outcomes.Adverse events: Monitoring and reporting of any adverse or serious adverse events related to the study procedures, including MRI and PET-CT scanning and [18F]FEOBV tracer administration.Measurements of plasma ACh concentrations aim to provide further insight into the relationship between whole body systemic cholinergic dysfunction and the PWS phenotype, such as muscle weakness, which may result from impaired neuromuscular junctions potentially linked to peripheral cholinergic nervous system dysfunction. | — |
Countries
Netherlands
Contacts
Public ContactA. M. Pereira Arias
Amsterdam UMC
Outcome results
None listed