A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Transcriptomic analysis
研究概览
简要总结
This is a 2-year follow-up study of a cohort of 35 CMT1A patients and 20 healthy volunteers. The main objective is identifying prognostic markers for CMT1A using multi-omics analysis. The study is recruiting subjects between the ages of 10 and 30.
The most common inherited neuropathy is Charcot-Marie-Tooth disease type 1A (CMT1A), caused by a duplication of the gene expressing PMP22. CMT1A patients develop symptoms in early childhood with variable progression and there is no established therapy until now. Therapy must start in childhood, before peripheral nerves degenerate. However, we lack easily obtainable biomarkers in early disease stages.
In CMT-MODs, we will identify disease and prognostic biomarkers in young CMT1A patients.
详细描述
The CMT-MODs project aims to conduct a multi-omics analysis (transcriptomics, proteomics, lipidomics) in young patients with early-stage CMT1A. This evaluation should enable the identification of prognostic and change-sensitive biomarkers for use in clinical trials.
A large cohort of CMT1A children, adolescents and young adults aged 10-30 years over 12 months applying the novel clinical outcome measures CMT Examination Score/CMT Neuropathy Score Version Version 2 Rasch versions (CMTES-R/CMTNSv2-R), the functional outcome measure CMT-FOM, pCMT-Qol, as well as a nerve conduction study (NCS) and quantitative MRI will be assessed.
Blood (and optional skin) samples will be taken and gene expression of the most promising candidates will be identified.
This assessment of CMT patients at early disease stages will allow CMT-MODs to establish biomarkers that may serve as a standard readout for disease severity and predict the disease course.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteer or patient who has given consent for participation in the study or, for minors, a healthy volunteer whose two parents have given consent for participation in the study.
- •Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed
- •Patient able to walk with or without assistance
排除标准
- •Healthy volunteer with neurological disorders
- •Healthy volunteer or patient with a contraindication to MRI,
- •Healthy volunteers or patient under 30 kg
- •Helathy volunteer on long-term therapy
- •Patient with other neuromuscular pathologies
- •Patient in a period of exclusion from another research protocol at the time of signing the consent/non-opposition form
- •Pregnant or breast-feeding women
- •Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women)
- •Subjects who cannot read and understand the French language well enough to be able to give their consent to participate in research
研究组 & 干预措施
Charcot-Marie-Tooth Neuropathy 1A
Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,
干预措施: Quantitative neuromuscular MRI (Other)
Charcot-Marie-Tooth Neuropathy 1A
Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,
干预措施: Skin biopsy (Other)
Charcot-Marie-Tooth Neuropathy 1A
Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,
干预措施: Clinical scores (Other)
Charcot-Marie-Tooth Neuropathy 1A
Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,
干预措施: Blood test (Other)
Charcot-Marie-Tooth Neuropathy 1A
Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,
干预措施: Patient Report Outcomes Measures (Other)
Healthy volunteers
Patient-matched controls
干预措施: Quantitative neuromuscular MRI (Other)
Healthy volunteers
Patient-matched controls
干预措施: Skin biopsy (Other)
Healthy volunteers
Patient-matched controls
干预措施: Clinical scores (Other)
Healthy volunteers
Patient-matched controls
干预措施: Blood test (Other)
结局指标
主要结局
Transcriptomic analysis
时间窗: Between inclusion (month 0) and one year later (month 12)
RNA seq on blood and skin tissues
Proteomic analysis
时间窗: Between inclusion (month 0) and one year later (month 12)
Label-free quantitative approach on blood and skin tissues
次要结局
- PROM (Patient Reported Outcomes Measures) : SF-12(Between inclusion (month 0), month 6, and one year later (month12))
- PROM (Patient Reported Outcomes Measures) : PGI-c(Between inclusion (month), month 6, and one year later (month 12))
- Clinical score : CMT-Peds(Between inclusion (month 0) and one year later (month 12))
- PROM (Patient Reported Outcomes Measures) : WALK-12(Between inclusion (month 0), month 6, and one year later (month 12))
- PROM (Patient Reported Outcomes Measures) : pCMT-QoL(Between inclusion (month 0), month 6, and one year later (month12))
- MRI muscle biomarkers : Fat Fraction measure(Between inclusion (month 0) and one year later (month12))
- Clinical score : ONLS(Between inclusion (month 0) and one year later (month12))
- MRI muscle biomarkers : Magnetization Transfer Ratio(Between inclusion (month 0) and one year later (month12))
- MRI muscle biomarkers : T2 relaxation time(Between inclusion (month 0) and one year later (month12))
- PROM (Patient Reported Outcomes Measures) : VAS(Between inclusion (month 0), month 6, and one year later (month 12))
- MRI muscle biomarkers : muscle volume(Between inclusion (month 0) and one year later (month12))
- Clinical score : CMT-FOM(Between inclusion (month 0) and one year later (month12))
- Clinical score : CMTES-R(Between inclusion (month 0) and one year later (month12))