Identifying Biomarkers & Dysregulated Biological Pathways in Blood and Urine of Congenital Central Hypoventilation Syndrome (CCHS) Patients
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Identification of dysregulated biological pathways and biomarkers in blood and urine of CCHS patients.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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.
- •Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.
研究组 & 干预措施
CCHS Patient Group
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.
干预措施: Blood and Urine Sampling (Biological)
CCHS Patient Group
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.
干预措施: Polysomnography (Device)
CCHS Patient Group
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.
干预措施: lung function tests (Other)
Matched Healthy Control Group
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.
干预措施: Blood and Urine Sampling (Biological)
Matched Healthy Control Group
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.
干预措施: Polysomnography (Device)
Matched Healthy Control Group
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.
干预措施: lung function tests (Other)
结局指标
主要结局
Identification of dysregulated biological pathways and biomarkers in blood and urine of CCHS patients.
时间窗: 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.
次要结局
- 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)