Charcot-Marie-Tooth Disease, Type Ia (Disorder) Clinical Trial
— INC-6602Official title:
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.
| Status | Recruiting |
| Enrollment | 1050 |
| Est. completion date | December 2026 |
| Est. primary completion date | December 2026 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | N/A and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Children's Hospital of Westmead | Sydney | New South Wales |
| Italy | C. Besta Neurological Institute | Milan | |
| United Kingdom | Dubowitz Neuromuscular Centre | London | |
| United Kingdom | National Hospital of Neurology and Neurosurgery | London | England |
| United States | University of Colorado Hospital | Aurora | Colorado |
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | Harvard/Massachusetts General Hospital | Boston | Massachusetts |
| United States | Connecticut Children's Medical Center | Hartford | Connecticut |
| United States | University of Iowa | Iowa City | Iowa |
| United States | Cedars-Sinai Medical Center | Los Angeles | California |
| United States | University of Minnesota | Maple Grove | Minnesota |
| United States | University of Miami | Miami | Florida |
| United States | Nemours Children's Clinic | Orlando | Florida |
| United States | Stanford University | Palo Alto | California |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | University of Rochester | Rochester | New York |
| Lead Sponsor | Collaborator |
|---|---|
| University of Iowa | Cedars-Sinai Medical Center, Children's Hospital of Philadelphia, Children's National Research Institute, Connecticut Children's Medical Center, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Johns Hopkins University, King's College Hospital NHS Trust, Massachusetts General Hospital, Muscular Dystrophy Association, National Institute of Neurological Disorders and Stroke (NINDS), Nemours Children's Clinic, Seattle Children's Hospital, St. Jude Children's Research Hospital, Stanford University, Sydney Children's Hospitals Network, The Hospital for Sick Children, University of Colorado, Denver, University of Miami, University of Michigan, University of Minnesota, University of Pennsylvania, University of Rochester |
United States, Australia, Italy, United Kingdom,
Montenegro G, Powell E, Huang J, Speziani F, Edwards YJ, Beecham G, Hulme W, Siskind C, Vance J, Shy M, Zuchner S. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann Neurol. 2011 Mar;69(3):464-70. doi: 10.1002/ana.2 — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers | 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 | |
| Primary | New genetic causes of CMT | 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 |