Charcot Marie Tooth Disease Clinical Trial
— INC-6601Official title:
Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Type (CMT1B), 2A (CMT2A), 4A (CMT4A), 4C (CMT4C), and Others
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
Status | Recruiting |
Enrollment | 5000 |
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 be seen in-person at a participating center for the initial visit. Inclusion Criteria - patients with CMT (all subtypes) 1. Patient has documented, pathogenic or likely pathogenic CMT-causing variant(s) OR 2. 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. 3. 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. 4. Patients whose clinical presentation is suggestive of CMT, but CMT type and variant are unknown will be characterized by the following categories: 1. Nerve conduction velocities: demyelinating, axonal, intermediate 2. Inheritance: dominant, recessive, X-linked, or unknown 5. 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). Inclusion Criteria - Controls 1. Person does not have a peripheral neuropathy, as determined by the investigator. 2. 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). EXCLUSION CRITERIA 1. Patient has a variant of uncertain significance that cannot be further classified following methods listed in the Inclusion Criteria. 2. Patient does not wish to be a part of the study or has not signed an informed consent form. 3. Patient is deemed inappropriate by the Site PI. |
Country | Name | City | State |
---|---|---|---|
Australia | University of Westmead | Sydney | New South Wales |
Canada | The Hospital for Sick Children | Toronto | Ontario |
Italy | C. Besta Neurological Institute | Milan | |
United Kingdom | National Hospital of Neurology and Neurosurgery | London | England |
United States | University of Michigan | Ann Arbor | Michigan |
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 | University of Connecticut/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 | St. Jude Children's Research Hospital | Memphis | Tennessee |
United States | University of Miami | Miami | Florida |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | Nemours Children's Health | Orlando | Florida |
United States | Nemours Children's Hospital | 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 |
United States | Seattle Children's Hospital | Seattle | Washington |
United States | Children's National Hospital | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Michael Shy | Cedars-Sinai Medical Center, Charcot-Marie-Tooth Association, Children's Hospital of Philadelphia, Connecticut Children's Medical Center, Dubowitz Neuromuscular Centre, 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), National Institutes of Health (NIH), Nemours Children's Hospital, Rare Diseases Clinical Research Network, Stanford University, Sydney Children's Hospitals Network, The National Hospital for Neurology and Neurosurgery, University of Colorado, Denver, University of Miami, University of Minnesota, University of Pennsylvania, University of Rochester |
United States, Australia, Canada, Italy, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | Minimal dataset | This includes diagnosis, family history, developmental history, walking ability, hand function, strength, sensation, and neurophysiology. | 1 year |
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