A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)

Study Overview
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Brief Summary
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Charcot-Marie-Tooth 4J (CMT4J) is a rare inherited peripheral neuropathy often characterized by rapidly progressive, asymmetrical upper and lower extremity weakness, muscle atrophy leading to loss of ambulation, respiratory compromise and premature death with no available treatment. The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with CMT4J. This natural history study is important to better understand disease course to be able to determine clinically meaningful outcome measures for use in future clinical trials.

Detailed Description
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Charcot-Marie-Tooth (CMT) diseases are the most common inherited motor and sensory neuropathies, composed of a group of pathologically and genetically distinct subtypes ranging from slowly to rapidly progressive disease. CMT4J is a rare subtype of CMT caused by mutations in the FIG4 gene. Pediatric-onset disease can often be characterized by rapid progression of muscle weakness and atrophy, culminating in loss of ambulation and respiratory compromise and premature death. Adult-onset CMT4J can present with a more variable disease course. No prospective natural history study for CMT4J has been reported. This study aims to prospectively investigate the natural history of CMT4J, and concurrently to identify potential outcome measures that could be used in future clinical trials. No investigational product will be provided in the study.

Official Title
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A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)

Conditions
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Charcot-Marie-Tooth Disease, Hereditary Motor and Sensory Neuropathy IV

Participation Criteria
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Eligibility Criteria
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Subjects must have a prior confirmed molecular (genetic) diagnosis of CMT4J by clinical presentation and genetic testing.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Charcot Marie-Tooth Pediatric Scale (CMTPedS) | This an 11 item scale is used in patients younger than 18 yrs of age and generates a linear score of disability. | Change is being assessed from baseline measures every 6 months for up to five years | 
| Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2) | This is a 36 point scale that monitors disease impairment and progression with a higher score signifies increased disability. | Change is being assessed from baseline measures every 6 months for up to five years | 
| Charcot Marie-Tooth Functional Outcome Measure (CMT-FOM) | This is a performance-based outcome assessment which measures limitations in functional abilities in adults. | Change is being assessed from baseline measures every 6 months for up to five years | 
| CMT Health Index (CMTHI) | The CMTHI is a disease-specific, adult patient reported outcome measure designed to capture the disease burden of inherited neuropathies in the context of a clinical trial. | Change is being assessed from baseline measures every 6 months for up to five years | 
| Magnetic Resonance Imaging (MRI) of the calf muscles without contrast | MRI of bilateral thigh and calf muscles will be performed to characterize the pattern of muscle involvement and evaluate the muscle fat fraction (MFF). | Change is being assessed from baseline measures every 6 months for up to five years | 
| Nerve Conduction Study (NCS) | NCS is an electrophysiological test to evaluate the sensory and motor responses in the upper and lower extremities. | Change is being assessed from baseline measures every 6 months for up to five years | 
| Pulmonary Function Test, sitting and lying (PFT) | The purpose of the PFT is to identify the severity and progression of pulmonary impairment, and will be performed every 12 months. | Change is being assessed from baseline measures every 12 months for up to five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMT4J