Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others

NCT01193075 | Recruiting DMC

• 2 other identifiers: INC-66011U54NS065712-01
• Study Type: observational
• Target: 5,000
• Locations: 5 countries
• Sites: 22

Brief Summary

This is an observational longitudinal study to determine the natural history and genotype-phenotype correlations of disease causing mutations in Charcot Marie Tooth disease (CMT) type 1B (CMT1B), 2A (CMT2A), 4A (CMT4A), and 4C (CMT4C). The investigators will also be determine the capability of the newly developed CMT Pediatric Scale (CMT Peds scale) and the Minimal Dataset to measure impairment and perform longitudinal measurements in patients with multiple forms of CMT over a five year window

Conditions

Charcot Marie Tooth Disease

Keywords

Charcot Marie Tooth disease; CMT; HMSN; HMN; HSN; CMT1; CMT2

Outcome Measures

Primary Outcomes (2)

• Charcot Marie Tooth Neuropathy Score (CMTNS)

  Charcot Marie Tooth Neuropathy Score (CMTNS) is a composite measure of disability based on a person's symptoms, signs, and electrophysiology. It is based on a 36 point scale, with 9 items each worth up to 4 points. A higher score signifies increased disability.

  1 year

• Minimal dataset

  This includes diagnosis, family history, developmental history, walking ability, hand function, strength, sensation, and neurophysiology.

  1 year

Study Arms (5)

CMT1B

Families/patients with genetically confirmed CMT1B

CMT2A

Families/patients with genetically confirmed CMT2A

CMT4A

Families/patients with genetically confirmed CMT4A

CMT4C

Families/patients with genetically confirmed CMT4C

All other CMT

Families/patients with all other forms of CMT or CMT that has not yet been genetically identified

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who present to a participating site and have Charcot Marie Tooth disease (CMT) will be recruited for participation.

You may qualify if:

• All patients must be seen in-person at a participating center for the initial visit.
• Patient has documented, pathogenic or likely pathogenic CMT-causing variant(s)
• Patient has a first- or second-degree family member (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented pathogenic or likely pathogenic CMT-causing variant AND a clear link between that family member and the affected patient AND a phenotype consistent with the diagnosis
• i. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a pathogenic or likely pathogenic variant, and the parent does not have any signs, symptoms, or electrophysiology consistent with the diagnosis, there is no clear link unless the parent has also been found to have the pathogenic or likely pathogenic variant such as in cases with reduced penetrance
• ii. In cases where clear links are not available, genetic testing is required for the patient or the family member who is not clearly affected.
• Patients who have a variant of uncertain significance, as determined by the laboratory performing the testing may still be included if one of the following circumstances applies:
• i. Variant is categorized as pathogenic or likely pathogenic per the ACMG variant interpretation guidelines. \[80, 81\]
• ii. Variant has been found in multiple affected people in a family and has not been found in unaffected family members. (Note - both affected and unaffected family members must be tested in this situation to be included).
• iii. The principal investigator and the site investigator agree that the variant(s) is (are) most likely pathogenic.
• Patients whose clinical presentation is suggestive of CMT, but CMT type and variant are unknown will be characterized by the following categories:
• Nerve conduction velocities: demyelinating, axonal, intermediate
• Inheritance: dominant, recessive, X-linked, or unknown
• Patient or patient's legally authorized representative has understood and signed an IRB approved consent form for the study. Teenagers (age 13 - 17 years) and cognitively impaired adults who are able to read and write must sign an assent form (depending on local ethics committee requirements).
• Person does not have a peripheral neuropathy, as determined by the investigator.
• Person has understood and signed an IRB approved consent form for the study. Teenagers (age 13-17 years) must sign an assent form (depending on local ethics committee requirements).

You may not qualify if:

• Patient does not wish to be a part of the study or has not signed an informed consent form.
• Patient is deemed inappropriate by the Site PI.

Sponsors & Collaborators

• Michael Shy: lead
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• Johns Hopkins University: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• King's College Hospital NHS Trust: collaborator
• Nemours Children's Hospital: collaborator
• Stanford University: collaborator
• University of Pennsylvania: collaborator
• University of Rochester: collaborator
• Children's Hospital of Philadelphia: collaborator
• Sydney Children's Hospitals Network: collaborator
• Rare Diseases Clinical Research Network: collaborator
• Muscular Dystrophy Association: collaborator
• National Institutes of Health (NIH): collaborator
• Charcot-Marie-Tooth Association: collaborator
• Massachusetts General Hospital: collaborator
• Cedars-Sinai Medical Center: collaborator
• University of Miami: collaborator
• University of Minnesota: collaborator
• Connecticut Children's Medical Center: collaborator
• University of Colorado, Denver: collaborator
• The National Hospital for Neurology and Neurosurgery: collaborator
• Dubowitz Neuromuscular Centre: collaborator

Study Sites (22)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

University of Connecticut/Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Nemours Children's Health

Orlando, Florida, 32827, United States

RECRUITING

Nemours Children's Hospital

Orlando, Florida, 32827, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

Harvard/Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

University of Westmead

Sydney, New South Wales, 2145, Australia

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1E8, Canada

RECRUITING

C. Besta Neurological Institute

Milan, Milan, Italy

RECRUITING

National Hospital of Neurology and Neurosurgery

London, England, WC1N 3BG, United Kingdom

RECRUITING

Related Publications (3)

• Fridman V, Sillau S, Acsadi G, Bacon C, Dooley K, Burns J, Day J, Feely S, Finkel RS, Grider T, Gutmann L, Herrmann DN, Kirk CA, Knause SA, Laura M, Lewis RA, Li J, Lloyd TE, Moroni I, Muntoni F, Pagliano E, Pisciotta C, Piscosquito G, Ramchandren S, Saporta M, Sadjadi R, Shy RR, Siskind CE, Sumner CJ, Walk D, Wilcox J, Yum SW, Zuchner S, Scherer SS, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium-Rare Diseases Clinical Research Network (INC-RDCRN). A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores. Neurology. 2020 Mar 3;94(9):e884-e896. doi: 10.1212/WNL.0000000000009035. Epub 2020 Feb 11.

  PMID: 32047073 DERIVED

• Panosyan FB, Laura M, Rossor AM, Pisciotta C, Piscosquito G, Burns J, Li J, Yum SW, Lewis RA, Day J, Horvath R, Herrmann DN, Shy ME, Pareyson D, Reilly MM, Scherer SS; Inherited Neuropathies Consortium-Rare Diseases Clinical Research Network (INC-RDCRN). Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1). Neurology. 2017 Aug 29;89(9):927-935. doi: 10.1212/WNL.0000000000004296. Epub 2017 Aug 2.

  PMID: 28768847 DERIVED

• Fridman V, Bundy B, Reilly MM, Pareyson D, Bacon C, Burns J, Day J, Feely S, Finkel RS, Grider T, Kirk CA, Herrmann DN, Laura M, Li J, Lloyd T, Sumner CJ, Muntoni F, Piscosquito G, Ramchandren S, Shy R, Siskind CE, Yum SW, Moroni I, Pagliano E, Zuchner S, Scherer SS, Shy ME; Inherited Neuropathies Consortium. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):873-8. doi: 10.1136/jnnp-2014-308826. Epub 2014 Nov 27.

  PMID: 25430934 DERIVED

Related Links

• Inherited Neuropathies Consortium Website

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy

Condition Hierarchy (Ancestors)

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

Study Officials

• Michael E Shy, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole M Kressin, MSN, RN

CONTACT

319-384-6362; UICMTClinic@uiowa.edu

Tiffany Grider, MS, CGC

CONTACT

319-384-6362; UICMTClinic@uiowa.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: September 1, 2010
• Study Start: April 1, 2010
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: For Observational/Longitudinal/Natural History/Epidemiology studies): For the current grant cycle, available data will be released to the repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first.
• Access Criteria: \- For the current grant cycle, once de-identified data is posted on dbGaP, a summary of the study is posted and individual participant data is accessed via a request through dbGaP.

Locations

IT (1); GB (1); US (18); CA (1); AU (1)