Charcot-Marie-Tooth Disease Type 1A
Conditions
Keywords
CMT1A, Fat Fraction, CMT Examination Score Rasch, CMT Functional Outcome Measure, Skin Biopsy, histological markers, MRI muscle
Brief summary
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.
Detailed description
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.
Interventions
Quantification of biomarkers as fat fraction, magnetization Transfer Ratio, muscular volume, relaxation time T2
OTHERSkin biopsy
Performed on the arm or index finger, depending on patient age
OTHERClinical scores
ONLS, CMTES-R, CMT-Peds, CMT-FOM
OTHERBlood test
10 ml sample
OTHERPatient Report Outcomes Measures
pCMT-QoL, EVA, WALK-12, PGI-c, SF-12
Sponsors
Association Française contre les Myopathies (AFM), Paris
University Medical Center Göttingen
Assistance Publique Hopitaux De Marseille
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Comparison of patient and healthy volunteers data at inclusion (M0) and 12 months (M12)
Eligibility
Sex/Gender
ALL
Age
10 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transcriptomic analysis | Between inclusion (month 0) and one year later (month 12) | RNA seq on blood and skin tissues |
| Proteomic analysis | Between inclusion (month 0) and one year later (month 12) | Label-free quantitative approach on blood and skin tissues |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI muscle biomarkers : T2 relaxation time | Between inclusion (month 0) and one year later (month12) | — |
| MRI muscle biomarkers : muscle volume | Between inclusion (month 0) and one year later (month12) | — |
| Clinical score : ONLS | Between inclusion (month 0) and one year later (month12) | Overall Neuropathy Limitations Scale |
| Clinical score : CMTES-R | Between inclusion (month 0) and one year later (month12) | CMT Examination Score |
| Clinical score : CMT-FOM | Between inclusion (month 0) and one year later (month12) | The CMT-Functional Outcome Measure |
| MRI muscle biomarkers : Fat Fraction measure | Between inclusion (month 0) and one year later (month12) | — |
| PROM (Patient Reported Outcomes Measures) : pCMT-QoL | Between inclusion (month 0), month 6, and one year later (month12) | Pediatrics CMT Questionnaire of Life |
| PROM (Patient Reported Outcomes Measures) : VAS | Between inclusion (month 0), month 6, and one year later (month 12) | Visual Analog Scale |
| PROM (Patient Reported Outcomes Measures) : WALK-12 | Between inclusion (month 0), month 6, and one year later (month 12) | — |
| PROM (Patient Reported Outcomes Measures) : PGI-c | Between inclusion (month), month 6, and one year later (month 12) | Patient's Global Impression of change scale |
| PROM (Patient Reported Outcomes Measures) : SF-12 | Between inclusion (month 0), month 6, and one year later (month12) | — |
| Clinical score : CMT-Peds | Between inclusion (month 0) and one year later (month 12) | Charcot-Marie-Tooth Disease Pediatric Scale |
| MRI muscle biomarkers : Magnetization Transfer Ratio | Between inclusion (month 0) and one year later (month12) | — |
Countries
France
Contacts
Primary ContactShahram ATTARIAN, PU-PH
Backup ContactEtienne FORTANIER, MD
Outcome results
None listed