Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07081464

Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Ondine Syndrome (Congenital Central Hypoventilation Syndrome) Apnea Cognition Disorders Cognitive Dysfunction Congenital central hypoventilation syndrome Dyssomnias Mental Disorders Nervous System Diseases Neurocognitive Disorders Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Apnea, Central Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

7 year–20 year

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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."

Who can participate

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

Inclusion criteria

  • Neonatal diagnosis of Ondine Syndrome.
  • PARM-type PHOX2B mutation.
  • Age 7 to 20 years.
  • Receiving nocturnal ventilation.
  • Consent obtained. Affiliated with social security.

Exclusion criteria

  • Severe autism spectrum disorder preventing test completion.
  • Legal guardianship or curatorship.

Treatment and study plan

MRI, EEG, Pupillometry

Other

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.

Primary outcomes

  1. Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks.

    Time frame: 24 hours

    Measurement of cognitive evoked potential P300 amplitude using a 64-electrode EEG system during Flanker and oddball paradigms to assess locus coeruleus function.

Secondary outcomes

  1. Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry.

    Time frame: 24 hours

  2. Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.

    Time frame: 24 hours

  3. Scores of socio-adaptive behavior from the Vineland neuropsychological test (Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning).

    Time frame: 24 hours

    Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning.

  4. Heart rate variability parameters from Holter ECG monitoring.

    Time frame: 24 hours

  5. Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.

    Time frame: 24 hours

Study contacts

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

Christophe DELCLAUX, MD, PhD

CONTACT

[email protected]

+33140038245

François-Xavier MAUVAIS, MD, PhD

CONTACT

[email protected]

+33140038245

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: ONDINE-LC

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jul 23, 2025
Registry last updated
Jul 23, 2025

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.