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

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.

Study Overview

• Status: Terminated
• Conditions: Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathy IV

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of CMT4J based on clinical presentation and genetic testing (known or suspected pathogenic mutation in FIG4).

Description

Subjects must have a prior confirmed molecular (genetic) diagnosis of CMT4J by clinical presentation and genetic testing.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neurogene Inc.
• Investigators: Study Director: Elise Beausoleil, Neurogene Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2019
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 15, 2022

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: CMT4J
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Stomatognathic Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Nervous System Malformations; Polyneuropathies; Peroxisomal Disorders; Tooth Diseases; Nerve Compression Syndromes; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Refsum Disease
• Other Study ID Numbers: CMT4J-100

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