Nerve function and structure in CMT, anti‑MAG neuropathy, and CIDP

Axonal Excitability and Ultrasound Patterns in Charcot-Marie-Tooth Disease and Other Demyelinating Disorders

This project will test nerve‑conduction, axonal‑excitability, skin biopsy, and ultrasound measures in adults with CMT, CIDP, or anti‑MAG neuropathy to see if they better describe nerve function and structure.

Quick facts

• Study type: Observational
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta (Academic / other)
• Locations: 1 site (Milan)
• Trial ID: NCT07461896 on ClinicalTrials.gov

What this trial studies

Researchers will perform conventional nerve‑conduction studies and axonal‑excitability testing using the TRONDF protocol in adults with selected forms of Charcot‑Marie‑Tooth disease and compare findings to patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and anti‑MAG neuropathy. The protocol also includes analysis of nerve fibers from skin biopsy in CMT patients and ultrasound imaging of nerves from the wrist to the axilla and of intrinsic hand muscles. Axonal‑excitability testing uses paired electrical stimuli with varying intensity and a conditioning stimulus of variable duration to probe axonal membrane and ion‑channel behavior. Physiological measures will be correlated with clinical and genetic classifications to explore potential diagnostic and prognostic value.

Who should consider this trial

Good fit: Adults (age ≥18) with a genetically confirmed CMT subtype or a clinical diagnosis of CIDP or anti‑MAG polyneuropathy are the ideal candidates.

Not a fit: Patients with neuropathy due to other causes (for example diabetes, chemotherapy, renal disease, or active alcohol abuse), recent cancer, pregnancy or nursing, known systemic diseases predisposing to neuropathy, or other central nervous system diseases are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this work could provide better tools to diagnose and monitor hereditary and immune‑mediated neuropathies and help guide treatment decisions.

How similar studies have performed: Preliminary studies of axonal‑excitability and nerve ultrasound have shown promise for revealing ion‑channel dysfunction and structural changes, though combining these modalities across hereditary and dysimmune neuropathies remains relatively novel.

Eligibility criteria

Inclusion Criteria:

1. The subject is ≥ 18 years old.

   AND:
2. A genetically confirmed diagnosis of one of the several CMT subtypes (i.e., CMT1A, CMT1B, CMTX1, CMT2I/J, CMT4B, CMT4D and CMT4J) OR
3. A clinical diagnosis of either Chronic Inflammatory Demyelinating Polyneuropathy or anti-MAG polyneuropathy

Exclusion Criteria:

1. Known neuropathy from another cause (e.g., diabetes, chronic renal insufficiency, medications, alcohol), including previous carpal tunnel syndrome surgery.
2. History of exposure to chemotherapeutic agents (e.g., bortezomib, vincristine, cisplatin, taxol, vedotin/auromycin-conjugated antibodies), or other medications (e.g., disulfuram, thalidomide, voriconizole, chronic colchicine use) that can cause neuropathy, active alcohol abuse.
3. History of cancer, other than skin cancer, within 5 years prior to enrollment.
4. Pregnancy or nursing.
5. Known systemic disease that predisposes to neuropathy.
6. Other central nervous system diseases.

Where this trial is running

Milan

• Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan, Italy (Recruiting)

Study contacts

• Principal investigator: Davide Pareyson, MD — Fondazione IRCCS Istituto Neurologico Carlo Besta
• Study coordinator: Davide Pareyson, MD

Conditions Charcot-Marie-Tooth; CMT1A; Chronic Inflammatory Demyelinating Polyneuropathy; Polyneuropathy Associated With Anti-MAG Antibodies; Anti-MAG Neuropathy; Neurophysiology; Axonal excitability; Ultrasound