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

NCT06997146 | Not Yet Recruiting

• 1 other identifier: CCHS Biomarkers
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Central Hypoventilation Syndrome (CCHS)

Keywords

CCHS; BIOMARKERS; POLYSOMNOGRAPHY; VENTILATORY SUPPORT; Metabolomic analyses

Outcome Measures

Primary Outcomes (1)

• Identification of dysregulated biological pathways and biomarkers in blood and urine of CCHS patients.

  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.

  Day 0 to Month 37

Secondary Outcomes (3)

• Identify new CCHS prognostic biomarkers

  Day 0 to Month 37

• Discover new candidate treatment targets

  Day 0 to Month 37

• Identify relevant repurposed drugs/supplements

  Day 0 to Month 37

Study Arms (2)

CCHS Patient Group

OTHER

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.

Biological: Blood and Urine Sampling; Device: Polysomnography; Other: lung function tests

Matched Healthy Control Group

OTHER

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.

Biological: Blood and Urine Sampling; Device: Polysomnography; Other: lung function tests

Interventions

Blood and Urine Sampling BIOLOGICAL

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.

CCHS Patient Group; Matched Healthy Control Group

Polysomnography DEVICE

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.

CCHS Patient Group; Matched Healthy Control Group

lung function tests OTHER

spirometry, ventilatory response to CO2

CCHS Patient Group; Matched Healthy Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CCHS patients :
• Age 18 years old or older;
• Carry a polyA expansion mutation in PHOX2B;
• Receive nocturnal mechanical ventilation;
• Patients that are under the care and treatment in the CCHS center: Hôpital Universitaire Pitié-Salpêtrière
• Written informed consent from the patient
• Affiliated to The French social security except patient on AME (state medical aid)
• Control group :
• Age 18 years old or older.
• Healthy with no major medical illnesses in the past year (such as diabetes, cancer, pregnancy, lungs disease).
• Matched for sex, age (+/- 3 years), origin and BMI category with a CCHS patient
• Written informed consent of the control
• Affiliated to The French social security except patient on AME (state medical aid)

You may not qualify if:

• CCHS patients :
• Age lower than 18 years old;
• Pregnancy or breastfeeding
• Patients with diaphragmatic (phrenic nerve) pacing;
• Patients with late onset CCHS;
• 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)
• Patients that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
• Patients who use medications that are likely to impair sleep structure
• Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.
• Control group :
• Age lower than 18 years old;
• Pregnancy or breastfeeding
• 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)
• Controls that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
• Controls who use medications that are likely to impair sleep structure.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

MeSH Terms

Conditions

Congenital central hypoventilation syndrome

Interventions

Blood Specimen Collection; Polysomnography; Respiratory Physiological Phenomena

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Monitoring, Physiologic; Circulatory and Respiratory Physiological Phenomena

Central Study Contacts

Maxime PATOUT PATOUT, MD

CONTACT

+33142178578; maxime.patout@aphp.fr

Alexis PEREZ CALOC Clinical project manager

CONTACT

alexis.caloc@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 2, 2028
• Study Completion (Estimated): December 2, 2028
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)