Clinical trial NCT04980807: Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls
Official title: An Open Observational Study of Clinical and Electrophysiological Outcomes in Male and Female Patients With CMT Type 1 & 2, and Aged-matched Healthy Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Charcot-Marie-Tooth Disease
Keywords: Neuromuscular Junction Transmission
Repetitive Nerve Stimulation
Neuromuscular Disease
Single Fiber EMG
Lead sponsor: NMD Pharma A/S
Sponsor class: INDUSTRY
Collaborators: name: Aarhus University Hospital
name: Ohio State University
First posted: 2021-07-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible CMT patients will be invited to participate at the respective study sites. Age matched healthy volunteers will be recruited through advertisement at the respective study sites

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

Eligibility criteria: 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

Exclusion Criteria for Healthy Volunteers

* Pregnant
* Requiring prescription medicines likely to interfere with electromyography (EMG) recordings
* Presence of current or previous medical condition which might interfere with participation in the study

Primary outcomes:
measure: Repetitive Nerve Stimulation - difference between CMT patients and healthy controls
timeFrame: Baseline
measure: Repetitive Nerve Stimulation - difference between CMT patients and healthy controls
timeFrame: Baseline
measure: Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls
timeFrame: Baseline
measure: Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls
timeFrame: Baseline
Secondary outcomes:
measure: Isometric Dynamometry - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Manual Muscle Testing - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: 9 Hole Peg Test - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: 6-Spot Step Test - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: 10-Meter Walk/run Test - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Timed Up and Go - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Berg Balance Scale - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: 6 Minute Walk Test - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Repetitive Nerve Stimulation - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
measure: Repetitive Nerve Stimulation - test reliability in patients with CMT
timeFrame: The test is performed at baseline and day 14, 28 and 42.
Other outcomes:
measure: CMTES2 Score
timeFrame: This test is performed at baseline in individuals with CMT disease
measure: Adverse Events
timeFrame: At baseline for healthy controls and from baseline until final visit at day 42 for CMT patients
measure: Tolerability of test procedures
timeFrame: Performed for each test at each visit (baseline, day 14, 28 and 42)
measure: Association between NMJ function and clinical function in CMT patients
timeFrame: Baseline
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Jutland
Study officials:
affiliation: Aarhus University Hospital
name: Henning Andersen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: William D Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References: