Charcot-Marie-Tooth Disease
Conditions
Keywords
Neuromuscular Junction Transmission, Repetitive Nerve Stimulation, Neuromuscular Disease, Single Fiber EMG
Brief summary
The primary aim of this study is to discover whether patients with CMT type 1 and 2 have neuromuscular junction transmission deficits. The secondary aim is to collect information of different clinical and electrophysiological test procedures to perform possible future clinical trials in CMT patients.
Detailed description
The study is a prospective observational pilot study involving two investigational sites: 1. Department of Neurology, Arhus University Hospital 2. Department of Neurology, Ohio State University A total of 20 patients with Charcot-Marie-Tooth (CMT) disease and 10 healthy age-matched controls will be included with each site including 10 CMT patients and 5 Healthy Controls. CMT patients will undergo electrophysiological (repetitive nerve stimulation and single fiber EMG analyses) and functional (different tests of muscle strength, fatigability, dexterity, and balance) testing on 4 separate occasions. Healthy controls will undergo electrophysiological testing at baseline only. To assess whether patients with CMT have deficits in NMJ transmission, results from repetitive nerve stimulation and single fiber EMG analyses in CMT patients will be compared to those obtained in healthy controls at baseline. To inform future clinical trials, results relability and tolerability estimates obtained from sequential electrophysiological and functional tests will be calculated
Interventions
None listed
Sponsors
Aarhus University Hospital
Ohio State University
NMD Pharma A/S
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for CMT Patients * Age ≥ 18 years * Diagnosis of CMT confirmed by: * Clinical presentation and electro diagnostics or genetics * Physical Features (all must apply): 1) Ambulation for at least 10 meters, without a brace 2) Left and right ankle plantar flexion Medical Research Council (MRC) grade 2 to 5, inclusive 3) Left and right ankle dorsiflexion MRC manual muscle testing (MMT) grade 2 to 4+, inclusive. * Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements * Stable concomitant medications for 2 months prior to enrolment * Signed written informed consent
Exclusion criteria
for CMT Patients * Severe deformity or ankle contracture that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength * Ulceration that would interfere with functional ability * Recent major surgery * Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study * Any disability or condition that would prevent completion of the study tasks * Moderate to severe Neuropathic or inflammatory/musculoskeletal pain that would interfere with performance of the tests * A diagnosis of a primary NMJ disorder such as myasthenia gravis, Lambert Eaton Myasthenic Syndrome or congenital myasthenic disorder Inclusion Criteria for Healthy Volunteers * Healthy male or female volunteers * Age ≥18 years * Able to give written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Repetitive Nerve Stimulation - difference between CMT patients and healthy controls | Baseline | Percentage decrement of CMAP for the trapezius |
| Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls | Baseline | Percentage blocking |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 10-Meter Walk/run Test - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test measures how fast the participant can walk/run 10 meters. |
| Berg Balance Scale - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | The test measures balance during different functional tasks. A total score is calculated as the sum of the individual scores for each item, with maximum value 56, with a lower score meaning worse balance |
| 6 Minute Walk Test - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test measures how far a person can walk in six minutes |
| Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | Percantage blocking |
| Repetitive Nerve Stimulation - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | Percentage decrement of CMAP for Trapezius |
| Isometric Dynamometry - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test will be used to evaluate maximum isometric strength |
| Manual Muscle Testing - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test is a physical examination of muscle strength. 15 muscle groups/motions will be tested. 13 of these are tested bilaterally. A total score between (0-280) is calculated |
| 9 Hole Peg Test - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This is a test of finger dexterity |
| 6-Spot Step Test - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test is a quantitative measure of lower extremity function |
| Timed Up and Go - test reliability in patients with CMT | The test is performed at baseline and day 14, 28 and 42. | This test measures how fast the participant can stand from a chair, walk 3 meters, turn around, return, and sit in the chair at a comfortable and safe pace |
Other
| Measure | Time frame | Description |
|---|---|---|
| Association between NMJ function and clinical function in CMT patients | Baseline | Correlation |
| Tolerability of test procedures | Performed for each test at each visit (baseline, day 14, 28 and 42) | The tolerability score assessed on a 0-9 rating scale (0=no discomfort to 9=worst possible discomfort) |
| CMTES2 Score | This test is performed at baseline in individuals with CMT disease | This test measures CMT disease severity. Total score is calculated as the sum of the 7 sub-scores with a maximum of score of 28 |
| Adverse Events | At baseline for healthy controls and from baseline until final visit at day 42 for CMT patients | Number of adverse events by severity |
Countries
Denmark, United States
Outcome results
None listed