Identifying Biomarkers & Dysregulated Biological Pathways in Blood and Urine of Congenital Central Hypoventilation Syndrome (CCHS) Patients

Not Applicable

Not yet recruiting

• Conditions: Congenital Central Hypoventilation Syndrome (CCHS)
• Interventions: Biological: Blood and Urine Sampling; Device: Polysomnography; Other: lung function tests

• Registration Number: NCT06997146
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The CCHS study is a prospective, open-label, monocentric, interventional study with diagnostic and prognostic objectives, conducted in two phases. The first phase aims to identify biomarkers and dysregulated biological pathways in patients with Congenital Central Hypoventilation Syndrome (CCHS) by analyzing blood and urine samples of patients and matched healthy controls collected at multiple timepoints during sleep and wakefulness. In the second phase, these candidate biomarkers and pathways will be validated in a larger cohort of patients and matched healthy controls using targeted assays such as RT-PCR and mass spectrometry-based metabolomic analysis. The primary objective is to uncover molecular signatures that could explain disease mechanisms, while the secondary objective is to explore potential biomarkers and treatment targets that can improve spontaneous breathing and CO₂ responsiveness in CCHS patients. The underlying hypothesis is that multi-omics profiling of blood and urine can reveal actionable insights into the pathophysiology of CCHS and support the development of targeted interventions.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-21
• Study First Submitted QC: 2025-05-21
• Last Update Submitted: 2025-05-21
• Study First Posted: 2025-05-30
• Last Update Posted: 2025-05-30
• Study Start: 2025-06-01
• Primary Completion: 2028-06-02
• Study Completion: 2028-06-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

CCHS patients :

1. Age 18 years old or older;
2. Carry a polyA expansion mutation in PHOX2B;
3. Receive nocturnal mechanical ventilation;
4. Patients that are under the care and treatment in the CCHS center: Hôpital Universitaire Pitié-Salpêtrière
5. Written informed consent from the patient
6. Affiliated to The French social security except patient on AME (state medical aid)

Control group :

1. Age 18 years old or older.
2. Healthy with no major medical illnesses in the past year (such as diabetes, cancer, pregnancy, lungs disease).
3. Matched for sex, age (+/- 3 years), origin and BMI category with a CCHS patient
4. Written informed consent of the control
5. Affiliated to The French social security except patient on AME (state medical aid)

Exclusion Criteria

CCHS patients :

1. Age lower than 18 years old;
2. Pregnancy or breastfeeding
3. Patients with diaphragmatic (phrenic nerve) pacing;
4. Patients with late onset CCHS;
5. Patients that were diagnosed with a major medical illnesses/condition other than CCHS in the past year (such as diabetes, cancer, lungs disease, a sleep disorder, or pregnancy)
6. Patients that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
7. Patients who use medications that are likely to impair sleep structure
8. Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.

Control group :

1. Age lower than 18 years old;
2. Pregnancy or breastfeeding
3. Controls that were diagnosed with a major medical illnesses/condition in the past year (such as diabetes, cancer, lungs disease, a sleep disorder, or pregnancy)
4. Controls that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
5. Controls who use medications that are likely to impair sleep structure.
6. Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CCHS Patient Group	Blood and Urine Sampling	Participants in this arm are individuals diagnosed with Congenital Central Hypoventilation Syndrome (CCHS). They will undergo blood and urine sample collection at various timepoints during sleep and wakefulness. Additionally, they will undergo polysomnography to monitor sleep-related breathing patterns and to assess respiratory function during sleep. The focus is on analyzing biomarkers and dysregulated biological pathways associated with CCHS, and comparing them to matched healthy controls.
CCHS Patient Group	Polysomnography	Participants in this arm are individuals diagnosed with Congenital Central Hypoventilation Syndrome (CCHS). They will undergo blood and urine sample collection at various timepoints during sleep and wakefulness. Additionally, they will undergo polysomnography to monitor sleep-related breathing patterns and to assess respiratory function during sleep. The focus is on analyzing biomarkers and dysregulated biological pathways associated with CCHS, and comparing them to matched healthy controls.
Matched Healthy Control Group	Blood and Urine Sampling	Participants in this arm are healthy individuals who are matched for sex, age, origin, and BMI with the CCHS patients. They will undergo the same blood and urine sample collection at various timepoints during sleep and wakefulness, and will also undergo polysomnography to assess normal sleep patterns and respiratory function during sleep. This group serves as a comparison to understand the biomarkers and biological pathways in CCHS patients.
Matched Healthy Control Group	Polysomnography	Participants in this arm are healthy individuals who are matched for sex, age, origin, and BMI with the CCHS patients. They will undergo the same blood and urine sample collection at various timepoints during sleep and wakefulness, and will also undergo polysomnography to assess normal sleep patterns and respiratory function during sleep. This group serves as a comparison to understand the biomarkers and biological pathways in CCHS patients.
CCHS Patient Group	lung function tests	Participants in this arm are individuals diagnosed with Congenital Central Hypoventilation Syndrome (CCHS). They will undergo blood and urine sample collection at various timepoints during sleep and wakefulness. Additionally, they will undergo polysomnography to monitor sleep-related breathing patterns and to assess respiratory function during sleep. The focus is on analyzing biomarkers and dysregulated biological pathways associated with CCHS, and comparing them to matched healthy controls.
Matched Healthy Control Group	lung function tests	Participants in this arm are healthy individuals who are matched for sex, age, origin, and BMI with the CCHS patients. They will undergo the same blood and urine sample collection at various timepoints during sleep and wakefulness, and will also undergo polysomnography to assess normal sleep patterns and respiratory function during sleep. This group serves as a comparison to understand the biomarkers and biological pathways in CCHS patients.

Primary Outcome Measures

Name	Time	Method
Identification of dysregulated biological pathways and biomarkers in blood and urine of CCHS patients.	Day 0 to Month 37	In the first phase of this study, candidate CCHS-related biomarkers and dysregulated pathways will be identified based on the analysis of the generated omics data. Candidate transcripts and metabolites that meet the criteria listed below will be further tested in the second targeted validation phase in an additional larger cohort of patients and matched controls. These will be sampled and analysed by specific tests (RT PCR or targeted metabolic analysis), that are relevant for each of the candidate transcripts and metabolites.; The following criteria will be employed in the analyses of both phases: 1. Significant alteration between patients and matched controls during sleep (and/or wakefulness).; 2. Significant alteration between sleep and wakefulness in controls.; 3. Significant alteration between sleep and wakefulness in patients.; 4. Significant alteration in the targeted validation phase, with a trend similar to the trend identified in phase I.

Secondary Outcome Measures

Name	Time	Method
Identify new CCHS prognostic biomarkers	Day 0 to Month 37	New CCHS prognostic biomarkers will be identified by analyzing significant correlations between biomarker levels (such as RNA, metabolites, etc.) and performance on breathing tests in CCHS patients.
Discover new candidate treatment targets	Day 0 to Month 37	The evaluation criteria for the identification and prioritization of new candidate treatment targets would include finding a solid scientific rational and defined and prioritized according to their parameters regarding pharmacodynamic-pharmacokinetic (PK/PD), ability to cross the blood brain barrier, drug developmental phase, regulatory status, intellectual property condition, and overall risk-benefit balance.
Identify relevant repurposed drugs/supplements	Day 0 to Month 37	Relevant repurposed drugs/supplements will be defined and prioritized according to their parameters regarding pharmacodynamic-pharmacokinetic (PK/PD), ability to cross the blood brain barrier, drug developmental phase, regulatory status, intellectual property condition, and overall risk-benefit balance.

Trial Locations

Locations (1)

Pitié-Salpêtrière Hospital; 🇫🇷 Paris, France