A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: CMT, CMT (Charcot Marie Tooth Disease), CMT - Charcot-Marie-Tooth Disease, CMT1A. Basic parameters: 10 years — 30 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Germany
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A) (CMT-MODs)
Overview
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, the investigators lack easily obtainable biomarkers in early disease stages. In peripheral nerves from young CMT1A rats, the invstigators found changes in gene regulation that predicted the clinical disease severity later in adulthood, and gene expression from blood samples in young CMT1A rats were strong predictors of the future disease course. In blood samples from adult CMT1A patients, changes in gene expression also correlated with disease severity, demonstrating that findings can be "translated" from CMT rats to patients. Objectives: In CMT-MODs, the investigators will identify disease and prognostic biomarkers in young CMT1A patients. Strategy/ Methodology: In a translational approach, the investigators will first perform a multi-omic analysis (transcriptomic and proteomic) in sciatic nerves, blood and skin of young CMT1A rats at two timepoints in order to identify novel early markers of disease severity. In parallel, the investigators will assess 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. Moreover, the following patient-reported outcome measures (PROMs) will also applied: VAS (pain, fatigue, cramps), WALK-12 and PGI-c. Blood (and optional skin) samples will be taken and gene expression of the most promising candidates, which the investigators originally identified in CMT rats, will be measured. Results: This unprecedented assessment of CMT patients and animal models 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. Impact: These novel diagnostic measures are urgently needed and will make clinical trials in early disease stages (children) possible in order to effectively treat and prevent CMT1A disease. Without effective biomarkers, promising preclinical therapeutic strategies cannot be translated to patients.
Primary outcome measures
- Charcot-Marie-Tooth Examination Score Rasch Analysis (CMTES-R) [Time frame: 12 months]
- Charcot-Marie-Tooth Neuropathy Score Version 2 Rasch Analysis (CMTNSv2-R) [Time frame: 12 months]
Secondary outcome measures (10)
- Charcot-Marie-Tooth Functional Outcome Measeure (CMT-FOM) [Time frame: 12 months]
- Short Form-12 (SF-12) [Time frame: 12 months]
- pCMT-QoL [Time frame: 12 months]
- Quantitative Mangetic Resonance Imaging (qMRI) [Time frame: 12 months]
- Visual Analogue Scale (VAS) for Pain, Fatigue, Cramps [Time frame: 12 months]
- Walking Impact Scale-12 (WALK12) [Time frame: 12 months]
- Patient Global Impression of Change (PGI-c) [Time frame: 12 months]
- Blood biomarkers [Time frame: 12 months]
- Skin biomarkers [Time frame: 12 months]
- Fibroblasts [Time frame: The biopsies are taken at baseline visit and will then be cultivated for future experiments]
Eligibility criteria
Inclusion criteria
- collaborative children, adolescents and young adults aged 10-30 years
- genetic diagnosis of CMT1A, or clinical diagnosis and genetic diagnosis in affected relatives
- able to walk with/ without support.
Exclusion criteria
- neuromuscular disorders other than CMT1A
- concomitant disease preventing correct patient evaluation and contraindication to qMRI
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Germany · 1 center
- University Medical Centre — Göttingen
Identifiers
NCT: NCT07476365 · 2024-03110