NCT07081464

Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)

Study of the Impact of Locus Coeruleus Dysfunction on Cognitive Function in Young Subjects With Ondine Syndrome

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 25 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 7 Years – 20 Years
• Healthy volunteers: —

Summary

This study investigates whether cognitive dysfunction in young patients with congenital central hypoventilation syndrome (Ondine Syndrome) is related to the severity of the disease and dysfunction of the locus coeruleus (a brainstem structure involved in autonomic control and cognition). The investigators will assess cognitive evoked potentials (P300 wave) using high-resolution EEG during attention tasks, pupillometry, brain MRI, neuropsychological tests, and heart rate variability. Patients with different severities of PHOX2B gene mutation (alanine expansions \<27 vs. ≥27) will be compared.

Detailed description

Ondine Syndrome (congenital central hypoventilation syndrome) is a rare autosomal dominant genetic disorder caused by mutations in PHOX2B. Patients require lifelong nocturnal ventilation and often have cognitive impairments. The cause of cognitive deficits is uncertain: possible hypoxic brain injury or direct effects of PHOX2B mutations on brain regions like the locus coeruleus. This cross-sectional study includes 21 patients aged 7-20 years with Ondine Syndrome and PARM-type (polyalanine repeat mutation) PHOX2B mutations, divided into moderate (\<27 alanine expansions) and severe (≥27 expansions) groups. During routine hospitalization, participants undergo: High-resolution EEG with evoked potentials during auditory and visual attention tasks to measure P300 wave amplitude. Pupillometry during the same tasks to assess locus coeruleus function. 3T (3 Tesla magnetic resonance imaging) MRI (anatomical and diffusion imaging) without sedation. Neuropsychological assessment with the Vineland test. Holter ECG to analyze heart rate variability. The goal is to link locus coeruleus dysfunction to disease severity and explore its impact on cognition, autonomic balance, and sleep."

Conditions

• Ondine Syndrome (Congenital Central Hypoventilation Syndrome)

Interventions

Type	Name	Description
OTHER	MRI, EEG, Pupillometry	Comparison of P300 wave amplitude, pupillometric responses, functional and structural brain connectivity, socio-adaptive function, cardiac autonomic balance between two phenotypic severity groups of young patients with Ondine Syndrome.

Timeline

• Start date: 2025-10-15
• Primary completion: 2027-10-15
• Completion: 2027-10-15
• First posted: 2025-07-23
• Last updated: 2025-07-23

Locations

1 site across 1 country: France