Ondine Syndrome (Congenital Central Hypoventilation Syndrome)ONDINE-LCNCT07081464
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
An observational study of Ondine Syndrome (Congenital Central Hypoventilation Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 7 to 20 years
- Conditions the study is for
- Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
- What is being tested?
- MRI, EEG, Pupillometry
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 15 Nov 2025to 15 Nov 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 20 years
- All sexes
- Child, Adult
Study population: Minors and young adults aged 7 to 20 years diagnosed neonatally with Ondine Syndrome, carrying a PARM-type PHOX2B mutation and requiring nocturnal ventilation.
Who may be able to join
- Neonatal diagnosis of Ondine Syndrome.
- PARM-type PHOX2B mutation.
- Age 7 to 20 years.
- Receiving nocturnal ventilation.
- Consent obtained. Affiliated with social security.
Who cannot join
- Severe autism spectrum disorder preventing test completion.
- Legal guardianship or curatorship.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Robert Debré Hospital
Paris, Ap-hp / DRCI, 75019
François-Xavier MAUVAIS, MD, PhD, +33140038245, francois-xavier.mauvais@aphp.fr
Christophe DELCLAUX, MD-PhD, +33140038245, christophe.delclaux@aphp.fr
About this study
Official title: Study of the Impact of Locus Coeruleus Dysfunction on Cognitive Function in Young Subjects With Ondine 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.
Read the 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."
- Being tested
- MRI, EEG, Pupillometry
- Keywords
- Locus Coeruleus, PHOX2B, Cognitive Dysfunction, EEG, Pupillometry, MRI, Ondine Syndrome
- Medical subject headings
- Sleep Apnea, Central, Congenital central hypoventilation syndrome, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI, EEG, PupillometryOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with severe Ondine syndrome (PHOX2B mutation with ≥ 27 alanine expansions) | Not described Receives: Other: MRI, EEG, Pupillometry | |
| Subjects with moderate Ondine syndrome (PHOX2B mutation with < 27 alanine expansions); | Not described Receives: Other: MRI, EEG, Pupillometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks.
Measurement of cognitive evoked potential P300 amplitude using a 64-electrode EEG system during Flanker and oddball paradigms to assess locus coeruleus function.
Measured: 24 hours
Secondary outcomes (5)
Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry.
Measured: 24 hours
Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.
Measured: 24 hours
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).
Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning.
Measured: 24 hours
Heart rate variability parameters from Holter ECG monitoring.
Measured: 24 hours
Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start15 Nov 2025
- Primary completion15 Nov 2027 (estimated)
- Study completion15 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ondine Syndrome (Congenital Central Hypoventilation Syndrome)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François-Xavier MAUVAIS, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07081464
- Sponsor's protocol ID
- APHP241606
- Other IDs
- N° IDRCB : 2025-A00156-43
- Acronym
- ONDINE-LC
- Status last verified
- Nov 2026
- First submitted
- 7 Jul 2025
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Impact of Locus Coeruleus Dysfunction on Cognitive Function in Young Subjects With Ondine Syndrome
- ClinicalTrials.gov ID
- NCT07081464
- Acronym / sponsor ID
- ONDINE-LC / APHP241606
- Keywords
- Locus Coeruleus, PHOX2B, Cognitive Dysfunction, EEG, Pupillometry, MRI, Ondine Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Nov 2025 (actual)
- Primary completion
- 15 Nov 2027 (estimated)
- Study completion
- 15 Nov 2027 (estimated)
- First posted
- 23 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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."
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects with severe Ondine syndrome (PHOX2B mutation with ≥ 27 alanine expansions) | – | Other: MRI, EEG, Pupillometry |
| Subjects with moderate Ondine syndrome (PHOX2B mutation with < 27 alanine expansions); | – | Other: MRI, EEG, Pupillometry |
Who may qualify
- Ages
- 7 to 20 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Minors and young adults aged 7 to 20 years diagnosed neonatally with Ondine Syndrome, carrying a PARM-type PHOX2B mutation and requiring nocturnal ventilation.
Key inclusion criteria (5 listed)
- Neonatal diagnosis of Ondine Syndrome.
- PARM-type PHOX2B mutation.
- Age 7 to 20 years.
- Receiving nocturnal ventilation.
- Consent obtained. Affiliated with social security.
Key exclusion criteria (2 listed)
- Severe autism spectrum disorder preventing test completion.
- Legal guardianship or curatorship.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI, EEG, PupillometryComparison 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. | Other | Subjects with moderate Ondine syndrome (PHOX2B mutation with < 27 alanine expansions);, Subjects with severe Ondine syndrome (PHOX2B mutation with ≥ 27 alanine expansions) |
Primary outcome
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.
5 secondary outcomes
Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry.
Time frame: 24 hours
Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.
Time frame: 24 hours
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
Heart rate variability parameters from Holter ECG monitoring.
Time frame: 24 hours
Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging.
Time frame: 24 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
Related trials for Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingObservational study
Neurocognition in Congenital Central Hypoventilation Syndrome (CCHS)
Congenital Central Hypoventilation Syndrome, Congenital Central Hypoventilation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
François-Xavier MAUVAIS, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ondine Syndrome (Congenital Central Hypoventilation Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact François-Xavier MAUVAIS, MD, PhD (+33140038245, francois-xavier.mauvais@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks. (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.