Genetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2 (INC-6602)

October 1, 2025 updated by: Michael Shy, University of Iowa

Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT

This project includes two projects. One is looking for new genes that cause Charcot Marie Tooth disease (CMT). The other is looking for genes that do not cause CMT, but may modify the symptoms a person has.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This project is to understand modifier genes and how they influence the severity of disease expression, along with identifying new forms of CMT which have not been genetically determined. Subjects who are eligible will either have CMT type 1A (CMT1A) or an unknown form of CMT. Blood will be drawn and sent to the University of Miami where they receive the coded sample and process it through exome sequencing. Subjects will be told that this is optional.

Study Type

Observational

Enrollment (Estimated)

1050

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2145
        • Recruiting
        • Children's Hospital of Westmead
        • Contact:
        • Principal Investigator:
          • Kayla Cornett, PhD
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • The Hospital for Sick Children
        • Principal Investigator:
          • Hernan Gonorazky, MD
        • Contact:
  • Italy
      • Milan, Italy
        • Recruiting
        • C. Besta Neurological Institute
        • Principal Investigator:
          • Davide Pareyson, MD
        • Contact:
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • Dubowitz Neuromuscular Centre
        • Principal Investigator:
          • Francesco Muntoni, MD
        • Contact:
    • England
      • London, England, United Kingdom, WC1N 3BG
        • Recruiting
        • National Hospital of Neurology and Neurosurgery
        • Principal Investigator:
          • Mary Reilly, MD
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Principal Investigator:
          • Robert Baloh, MD, PhD
        • Principal Investigator:
          • Richard A Lewis, MD
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • John Day, MD, PhD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital
        • Principal Investigator:
          • Vera Fridman, MD
        • Contact:
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Medical Center
        • Principal Investigator:
          • Gyula Acsadi, MD, PhD
        • Contact:
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Stephan Zuchner, MD, PhD
        • Principal Investigator:
          • Mario Saporta, MD, PhD, MBA
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Michael E Shy, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins University
        • Contact:
        • Principal Investigator:
          • Bipasha Mukherjee-Clavin, MD, PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Harvard/Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Reza Seyedsadjadi, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Brett McCray, MD, PhD
    • Minnesota
      • Maple Grove, Minnesota, United States, 55369
        • Recruiting
        • University of Minnesota
        • Contact:
        • Principal Investigator:
          • David Walk, MD
    • New York
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
        • Principal Investigator:
          • David Herrmann, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina
        • Contact:
        • Principal Investigator:
          • Rebecca Traub, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Sabrina Yum, MD
        • Sub-Investigator:
          • Tim Estilow
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • St. Jude Children's Research Hospital
        • Principal Investigator:
          • Richard Finkel, MD
        • Principal Investigator:
          • Joshua Burns, PhD
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Jun Li, MD, PhD
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Principal Investigator:
          • Seth Perlman, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients participating in Inherited Neuropathies Consortium (INC)-6601 and meeting eligibility criteria for this study will be recruited.

Description

Inclusion Criteria:

All patients must agree to take part in the study and sign a consent form. A teenager (age 13-17 years) considering enrolling must agree to take part in the study and sign an assent form (depending on local ethics committee requirements).

Additional inclusion criteria are described below.

Inclusion Criteria: CMT1A Gene Modifier Study

Patients must have at least one of the following:

  1. Patient has a documented PMP22 duplication. AND/OR
  2. Patient has a first or second degree relative (parent, child, sibling, half- sibling, aunt, uncle, grandparent, grandchild, niece, or nephew) with a documented PMP22 duplication AND a clear link between that family member and the affected patient AND a phenotype consistent with CMT1A.

i. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a PMP22 duplication, and the parent does not have any signs, symptoms, or electrophysiology consistent with CMT1A, there is no clear link.

ii. In cases where clear links are not available, genetic testing is required for the patient or the first degree family member who is not clearly affected.

Inclusion Criteria - Patients for CMT Exome Project

a. Patient has demonstrated neuropathy on nerve conduction studies or clinically diagnosed genetic neuropathy, in the opinion of the investigator or genetic counsellor.

Inclusion Criteria - Controls for CMT Exome Project

  1. Person is a family member of a CMT patient who is enrolled in the CMT Exome Project.

    AND one of the following:

  2. Person does not have a peripheral neuropathy, in the opinion of the investigator or genetic counsellor.

    OR

  3. Person is suspected to have a peripheral neuropathy, but has not been examined at an INC site.

Exclusion Criteria

  1. Patient does not wish to participate or does not sign a consent form.
  2. For CMT Exome Project, patient has a genetically confirmed form of CMT (i.e. mutation in MFN2 causing CMT2A, mutation in GARS causing CMT2D, etc.).
  3. Patients with known neuropathy from a non-genetic source, such as chemotherapies (i.e. Vincristine, Taxol, Cisplatin), diabetes, alcoholism will be evaluated independently so that genetic contributions to their effects on CMT1A phenotypes can also be analyzed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
CMT1A
Families/people with genetically defined CMT1A
Genetically undefined CMT
Families/people with genetically undefined CMT with common causes ruled out.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers
Time Frame: once
While the same genetic change - an extra copy of PMP22 - causes CMT1A by definition, it is unclear why some people have more severe symptoms and some have less severe. We are looking for genetic modifiers - changes in the DNA that may be causing the differences in symptoms.
once
New genetic causes of CMT
Time Frame: Once
At least 33% of people with CMT have an unknown or genetically un-found form of the condition. We are looking for additional genes that cause CMT when mutated.
Once

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Iowa

Collaborators

Johns Hopkins University
University of Colorado, Denver
King's College Hospital NHS Trust
The Hospital for Sick Children
Massachusetts General Hospital
Children's Hospital of Philadelphia
University of Pennsylvania
University of Miami
National Institute of Neurological Disorders and Stroke (NINDS)
University of Michigan
Seattle Children's Hospital
Stanford University
St. Jude Children's Research Hospital
University of Minnesota
Cedars-Sinai Medical Center
University of Rochester
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Children's National Research Institute
Nemours Children's Clinic
Sydney Children's Hospitals Network
Connecticut Children's Medical Center
Muscular Dystrophy Association

Investigators

  • Principal Investigator: Michael E Shy, MD, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2010

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

August 9, 2010

First Submitted That Met QC Criteria

August 31, 2010

First Posted (Estimated)

September 1, 2010

Study Record Updates

Last Update Posted (Estimated)

October 7, 2025

Last Update Submitted That Met QC Criteria

October 1, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INC-6602
  • 1U54NS065712-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified RDCRN data is submitted to an ORDR-designated repository. For the current grant cycle, that repository has been dbGaP

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Charcot-Marie-Tooth Disease, Type Ia (Disorder)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe