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

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ClinicalTrials.gov Identifier: NCT01193088
Recruitment Status : Recruiting
First Posted : September 1, 2010
Last Update Posted : September 13, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease
Charcot-Marie-Tooth Disease, Type Ia (Disorder) HMSN

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 Design

Study Type : Observational
Estimated Enrollment : 1050 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT
Actual Study Start Date : April 2010
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Groups and Cohorts

Genetically undefined CMT
Families/people with genetically undefined CMT with common causes ruled out.

Outcome Measures

Primary Outcome Measures :
  1. 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.

  2. 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.

Biospecimen Retention:   Samples With DNA
DNA extracted from whole blood. Filter cards with blood spots.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
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.

Inclusion Criteria:

Patient MUST be seen in person at one of the clinical sites involved in this study.

Charcot Marie Tooth disease type 1A (CMT1A) modifier gene study

  • Patient has a documented PMP22 duplication OR
  • 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.


  • Patient has agreed to take part in the study and has signed a consent form.
  • A teenager (ages 13-17) considering enrolling must agree to take part in the study and sign an assent form

Inclusion Criteria - CMT Exome Project

  1. Patient has demonstrated neuropathy on nerve conduction studies or a clinically diagnosed genetic neuropathy.
  2. Patient or first or second degree family member with a clear link as described in the CMT1A Inclusion Criteria part b has had negative MFN2 genetic testing, if has an axonal form of CMT (nerve conductions greater than 38 m/s) or negative testing for PMP22 duplication, deletion, sequencing, MPZ, and GJB1 if a demyelinating form of CMT is present (<38 m/s).
  3. More than one family member is willing eligible to participate.

i. Sample pedigrees showing optimal degrees of relationship are shown below. ii. Participation includes being able to complete all aspects of the study, including the giving informed consent, having a brief physical examination, and providing a DNA sample.

d. Patient has agreed to take part in the study and has signed a consent form. e. A teenager (ages 13-17) considering enrolling must agree to take part in the study and sign an assent form.

Inclusion Criteria - Controls

  1. Person does not have a peripheral neuropathy, as determined by the investigator.
  2. Person has understood the study and signed an IRB approved consent form. Teenagers (age 13-17 years) must sign an assent form.

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. 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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01193088

Contact: Shawna Feely, MS, CGC 319-384-6362 UICMTClinic@uiowa.edu
Contact: Tiffany Grider, MS, CGC 319-384-6362 UICMTClinic@uiowa.edu

  Show 22 Study Locations
Sponsors and Collaborators
University of Iowa
National Institute of Neurological Disorders and Stroke (NINDS)
Muscular Dystrophy Association
University of Rochester
University of Pennsylvania
King's College Hospital NHS Trust
Sydney Children's Hospitals Network
Children's Hospital of Philadelphia
University of Miami
Johns Hopkins University
University of Washington
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Cedars-Sinai Medical Center
Nemours Children's Clinic
Stanford University
University of Michigan
Vanderbilt University Medical Center
Principal Investigator: Michael E Shy, MD University of Iowa
More Information

Additional Information:
Responsible Party: Michael Shy, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01193088     History of Changes
Other Study ID Numbers: INC-6602
1U54NS065712-01 ( U.S. NIH Grant/Contract )
First Posted: September 1, 2010    Key Record Dates
Last Update Posted: September 13, 2017
Last Verified: September 2017

Keywords provided by Michael Shy, University of Iowa:

Additional relevant MeSH terms:
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Nervous System Malformations
Congenital Abnormalities
Matrix Metalloproteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action