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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Iowa
Sponsor:
Collaborators:
Muscular Dystrophy Association
University of Rochester
University of Pennsylvania
University College London Hospitals
The Children's Hospital at Westmead
Children's Hospital of Philadelphia
University of Miami
Johns Hopkins University
University of Washington
Information provided by (Responsible Party):
Michael Shy, Wayne State University
ClinicalTrials.gov Identifier:
NCT01193088
First received: August 9, 2010
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers [ Time Frame: once ] [ Designated as safety issue: No ]
    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.

  • New genetic causes of CMT [ Time Frame: Once ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 1050
Study Start Date: April 2010
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
CMT1A
Genetically undefined CMT
Families with at least 3 affected individuals, at least second degree relative apart.

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.

  Eligibility

Genders Eligible for Study:   Both
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.

Criteria

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.

AND

  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01193088

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

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Shawna Feely, MS, CGC    319-384-6362    UICMTClinic@uiowa.edu   
Principal Investigator: Michael E Shy, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
Contact: Andrea Kelley    443-287-0627    akelle12@jhmi.edu   
Principal Investigator: Tom Lloyd, MD         
Principal Investigator: Charlotte Sumner, MD         
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Janet Sowden    585-275-1267    janet_sowden@urmc.rochester.edu   
Principal Investigator: David Herrmann, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Donnette Paris    267-426-7167    Paris@email.chop.edu   
Principal Investigator: Richard Finkel, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Meryl Candor    215-349-5313    Meryl.Candor@uphs.upenn.edu   
Principal Investigator: Steven Scherer, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98124-1889
Contact: Corrie Smith, MS    206-598-3462    corrieo@u.washington.edu   
Principal Investigator: Tom Bird, MD         
Australia, New South Wales
Children's Hospital of Westmead Recruiting
Sydney, New South Wales, Australia, 2145
Contact: Natalie Gabrael    +61 2 9845 1904    natalig1@chw.edu.au   
Principal Investigator: Joshua Burns, PhD         
Italy
C. Besta Neurological Institute Recruiting
Milan, Italy
Contact: Chiara Marchesi    +39-02 2394 3001    chiara.marchesi@istituto-besta.it   
Principal Investigator: Davide Pareyson, MD         
United Kingdom
National Hospital of Neurology and Neurosurgery Recruiting
London, England, United Kingdom, WC1N 3BG
Contact: Jacky Molyneaux,    +44 207 380 6852    j.molyneaux@ion.ucl.ac.uk   
Principal Investigator: Mary Reilly, MD         
Sponsors and Collaborators
University of Iowa
Muscular Dystrophy Association
University of Rochester
University of Pennsylvania
University College London Hospitals
The Children's Hospital at Westmead
Children's Hospital of Philadelphia
University of Miami
Johns Hopkins University
University of Washington
Investigators
Principal Investigator: Michael E Shy, MD Wayne State University
  More Information

Additional Information:
Publications:
Responsible Party: Michael Shy, Professor, Wayne State University
ClinicalTrials.gov Identifier: NCT01193088     History of Changes
Other Study ID Numbers: INC-6602, 1U54NS065712-01
Study First Received: August 9, 2010
Last Updated: March 25, 2014
Health Authority: Australia: Human Research Ethics Committee
United Kingdom: Research Ethics Committee
United States: Institutional Review Board
Italy: Ethics Committee

Keywords provided by University of Iowa:
CMT
CMT1A

Additional relevant MeSH terms:
Hereditary Sensory and Motor Neuropathy
Polyneuropathies
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Tooth Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Nervous System Diseases
Nervous System Malformations
Neurodegenerative Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Stomatognathic Diseases

ClinicalTrials.gov processed this record on October 23, 2014