Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT-MODS)

A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)

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.

Study Overview

• Status: Recruiting
• Conditions: Charcot-Marie-Tooth Disease Type 1A
• Intervention / Treatment: Other: Quantitative neuromuscular MRI; Other: Skin biopsy; Other: Clinical scores; Other: Blood test; Other: Patient Report Outcomes Measures

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.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Etienne FORTANIER, MD; Phone Number: +33 04 91 38 65 79; Email: etienne.fortanier@ap-hm.fr
• Study Contact Backup: Name: Shahram ATTARIAN, PU-PH; Phone Number: +33 04 91 38 65 79; Email: shahram.attarian@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Assistance Publique - Hopitaux de Marseille
    • Principal Investigator: Shahram ATTARIAN, MD
    • Contact: François CREMIEUX, Managing Director; Phone Number: +33 04 91 38 27 47; Email: promotion.interne@ap-hm.fr
    • Sub-Investigator: Etienne FORTANIER, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Charcot-Marie-Tooth Neuropathy 1A; Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed,	Other: Quantitative neuromuscular MRI; Quantification of biomarkers as fat fraction, magnetization Transfer Ratio, muscular volume, relaxation time T2; Other: Skin biopsy; Performed on the arm or index finger, depending on patient age; Other: Clinical scores; ONLS, CMTES-R, CMT-Peds, CMT-FOM; Other: Blood test; 10 ml sample; Other: Patient Report Outcomes Measures; pCMT-QoL, EVA, WALK-12, PGI-c, SF-12
Other: Healthy volunteers; Patient-matched controls	Other: Quantitative neuromuscular MRI; Quantification of biomarkers as fat fraction, magnetization Transfer Ratio, muscular volume, relaxation time T2; Other: Skin biopsy; Performed on the arm or index finger, depending on patient age; Other: Clinical scores; ONLS, CMTES-R, CMT-Peds, CMT-FOM; Other: Blood test; 10 ml sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptomic analysis	RNA seq on blood and skin tissues	Between inclusion (month 0) and one year later (month 12)
Proteomic analysis	Label-free quantitative approach on blood and skin tissues	Between inclusion (month 0) and one year later (month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI muscle biomarkers : Fat Fraction measure		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)
MRI muscle biomarkers : muscle volume		Between inclusion (month 0) and one year later (month12)
Clinical score : ONLS	Overall Neuropathy Limitations Scale	Between inclusion (month 0) and one year later (month12)
Clinical score : CMTES-R	CMT Examination Score	Between inclusion (month 0) and one year later (month12)
Clinical score : CMT-FOM	The CMT-Functional Outcome Measure	Between inclusion (month 0) and one year later (month12)
Clinical score : CMT-Peds	Charcot-Marie-Tooth Disease Pediatric Scale	Between inclusion (month 0) and one year later (month 12)
PROM (Patient Reported Outcomes Measures) : pCMT-QoL	Pediatrics CMT Questionnaire of Life	Between inclusion (month 0), month 6, and one year later (month12)
PROM (Patient Reported Outcomes Measures) : VAS	Visual Analog Scale	Between inclusion (month 0), month 6, 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) : PGI-c	Patient's Global Impression of change scale	Between inclusion (month), month 6, and one year later (month 12)
PROM (Patient Reported Outcomes Measures) : SF-12		Between inclusion (month 0), month 6, and one year later (month12)

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Collaborators: Association Française contre les Myopathies (AFM), Paris; University Medical Center Göttingen
• Investigators: Study Director: François Crémieux, Assistance Publique - Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): June 24, 2025
• Primary Completion (Estimated): June 24, 2027
• Study Completion (Estimated): June 24, 2028

Study Registration Dates

• First Submitted: June 13, 2025
• First Submitted That Met QC Criteria: June 24, 2025
• First Posted (Actual): July 3, 2025

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Skin Biopsy; CMT1A; Fat Fraction; CMT Examination Score Rasch; CMT Functional Outcome Measure; histological markers; MRI muscle
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: RCAPHM24_0381; 2024-A02403-44 (Other Identifier: ID RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No