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

NCT07476365 | Recruiting DMC

• 1 other identifier: 2024-03110
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CMT; CMT - Charcot-Marie-Tooth Disease; CMT1A; CMT (Charcot Marie Tooth Disease); CMT 1A

Keywords

CMT1A children; blood-derived prognostic biomarkers; MRI biomarkers; transcriptomics; disease modifier; animal model

Outcome Measures

Primary Outcomes (2)

• Charcot-Marie-Tooth Examination Score Rasch Analysis (CMTES-R)

  The Charcot-Marie-Tooth Examination Score Rasch Version (CMTES-R) is a refined version of the Charcot-Marie-Tooth Examination Score (CMTES), which is used to assess disease severity in Charcot-Marie-Tooth disease (CMT). The Rasch version applies Rasch analysis, a statistical method that ensures the scale measures disease severity in a linear and more reliable way. Minimum Score (Best Condition): 0 Indicates no clinical impairment (normal strength, sensation, and reflexes). Maximum Score (Worst Condition): 32 Reflects severe disability, with profound weakness, loss of sensation, and absent reflexes.

  12 months

• Charcot-Marie-Tooth Neuropathy Score Version 2 Rasch Analysis (CMTNSv2-R)

  The Charcot-Marie-Tooth Neuropathy Score Version 2 Rasch Version (CMTNSv2-R) is a refined version of the Charcot-Marie-Tooth Neuropathy Score (CMTNSv2), optimized using Rasch analysis for improved measurement of disease severity. Minimum Score (Best Condition): 0 Indicates no clinical impairment (normal strength, sensation, and reflexes). Maximum Score (Worst Condition): 36 Reflects severe disability, with profound weakness, loss of sensation, and absent reflexes.

  12 months

Secondary Outcomes (10)

• Charcot-Marie-Tooth Functional Outcome Measeure (CMT-FOM)

  12 months

• Short Form-12 (SF-12)

  12 months

• pCMT-QoL

  12 months

• Quantitative Mangetic Resonance Imaging (qMRI)

  12 months

• Visual Analogue Scale (VAS) for Pain, Fatigue, Cramps

  12 months

Study Arms (2)

CMT1A patients

70

Controls

40

Eligibility Criteria

• Age: 10 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Outpatients clinics, patient support groups, German CMT registry

You may qualify if:

• 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.

You may not qualify if:

• neuromuscular disorders other than CMT1A
• concomitant disease preventing correct patient evaluation and contraindication to qMRI

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: collaborator
• University Medical Center Goettingen: lead

Study Sites (1)

University Medical Centre

Göttingen, 37075, Germany

RECRUITING

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Disease Models, Animal

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Animal Diseases

Study Officials

• Michael W Sereda

  University Medical Centre Göttingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael W Sereda, Prof. of Neurology

CONTACT

+49 551 3964162; sereda@mpinat.mpg.de

Beschan Ahmad

CONTACT

beschan.ahmad@med.uni-goettingen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. of Neurology

Study Record Dates

• First Submitted: February 23, 2025
• First Posted: March 17, 2026
• Study Start: March 24, 2025
• Primary Completion: June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)