Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls (ESTABLISH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04980807
Recruitment Status : Recruiting
First Posted : July 28, 2021
Last Update Posted : July 28, 2021
Sponsor:
Collaborators:
Aarhus University Hospital
Ohio State University
Information provided by (Responsible Party):
NMD Pharma A/S

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.


Condition or disease
Charcot-Marie-Tooth Disease

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

Layout table for study information
Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Prospective
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
Actual Study Start Date : April 7, 2021
Estimated Primary Completion Date : April 7, 2022
Estimated Study Completion Date : April 7, 2022


Group/Cohort
CMT Patients
Individuals with Charcot-Marie-Tooth Disease Types 1 and 2.
Healthy Controls
Healthy age-matched volunteers



Primary Outcome Measures :
  1. Repetitive Nerve Stimulation - difference between CMT patients and healthy controls [ Time Frame: Baseline ]
    Percentage decrement of CMAP for the trapezius

  2. Repetitive Nerve Stimulation - difference between CMT patients and healthy controls [ Time Frame: Baseline ]
    Percentage decrement of CMAP for abductor pollicis brevis

  3. Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls [ Time Frame: Baseline ]
    Percentage blocking

  4. Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls [ Time Frame: Baseline ]
    Jitter


Secondary Outcome Measures :
  1. Isometric Dynamometry - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    This test will be used to evaluate maximum isometric strength

  2. Manual Muscle Testing - test reliability in patients with CMT [ Time Frame: 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

  3. 9 Hole Peg Test - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    This is a test of finger dexterity

  4. 6-Spot Step Test - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    This test is a quantitative measure of lower extremity function

  5. 10-Meter Walk/run Test - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    This test measures how fast the participant can walk/run 10 meters.

  6. Timed Up and Go - test reliability in patients with CMT [ Time Frame: 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

  7. Berg Balance Scale - test reliability in patients with CMT [ Time Frame: 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

  8. 6 Minute Walk Test - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    This test measures how far a person can walk in six minutes

  9. Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    Percantage blocking

  10. Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    Jitter

  11. Repetitive Nerve Stimulation - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    Percentage decrement of CMAP for Trapezius

  12. Repetitive Nerve Stimulation - test reliability in patients with CMT [ Time Frame: The test is performed at baseline and day 14, 28 and 42. ]
    Percentage decrement of CMAP for abductor pollicis brevis


Other Outcome Measures:
  1. CMTES2 Score [ Time Frame: 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

  2. Adverse Events [ Time Frame: At baseline for healthy controls and from baseline until final visit at day 42 for CMT patients ]
    Number of adverse events by severity

  3. Tolerability of test procedures [ Time Frame: 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)

  4. Association between NMJ function and clinical function in CMT patients [ Time Frame: Baseline ]
    Correlation



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04980807


Contacts
Layout table for location contacts
Contact: Thomas S Groennebaek, PhD +4560122451 tsg@nmdpharma.com
Contact: Jane Bold, PhD jb@nmdpharma.com

Locations
Layout table for location information
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: William D Arnold, MD       William.Arnold@osumc.edu   
Contact: Kristina Kelly, PT, DPT, EdM       Kristina.Kelly@osumc.edu   
Principal Investigator: William D Arnold, MD         
Sub-Investigator: Kristina Kelly, PT, DPT, EdM         
Denmark
Aarhus University Hospital Recruiting
Aarhus, Jutland, Denmark, 8200
Contact: Henning Andersen, MD PhD       hennande@rm.dk   
Contact: Helga H Lillevang, MD       hehaah@rm.dk   
Principal Investigator: Henning Andersen, MD PhD         
Sub-Investigator: Hatice Tankisi, MD PhD         
Sub-Investigator: Helga H Lillevang, MD         
Sponsors and Collaborators
NMD Pharma A/S
Aarhus University Hospital
Ohio State University
Investigators
Layout table for investigator information
Principal Investigator: Henning Andersen, MD, PhD Aarhus University Hospital
Principal Investigator: William D Arnold, MD Ohio State University
Layout table for additonal information
Responsible Party: NMD Pharma A/S
ClinicalTrials.gov Identifier: NCT04980807    
Other Study ID Numbers: CMT Observational
First Posted: July 28, 2021    Key Record Dates
Last Update Posted: July 28, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NMD Pharma A/S:
Neuromuscular Junction Transmission
Repetitive Nerve Stimulation
Neuromuscular Disease
Single Fiber EMG
Additional relevant MeSH terms:
Layout table for MeSH terms
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn