Congenital Central Hypoventilation Syndrome (CCHS)
Conditions
Keywords
CCHS, BIOMARKERS, POLYSOMNOGRAPHY, VENTILATORY SUPPORT, Metabolomic analyses
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.
Interventions
BIOLOGICALBlood and Urine Sampling
Collection of 10 mL of blood (separated into aliquots for RNA-seq and metabolomic analysis) and 5 mL of urine from participants at various timepoints during sleep and wakefulness. These samples will be used to analyze biomarkers and dysregulated biological pathways related to CCHS.
DEVICEPolysomnography
Participants will undergo polysomnography to assess sleep patterns and respiratory function during sleep. This will help evaluate any sleep-related breathing abnormalities in patients with CCHS and compare them with healthy controls.
OTHERlung function tests
spirometry, ventilatory response to CO2
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Contacts
Primary ContactMaxime PATOUT PATOUT, MD
Backup ContactAlexis PEREZ CALOC Clinical project manager
Outcome results
None listed