Contractile Properties of Hypertrofic Muscles in Patients With Non-Dystrophic Myotonia

In myotonia congenita (MC), mutations in the CLCN1 gene coding a key chloride channel expressed in muscle cells cause myotonia. On examination, the myotonia can be demonstrated as delayed muscle relaxation of muscle contractions after mechanical stimulations. Existing literature describe no muscle weakness in MC patients, however a recent muscle MRI study in non-dystrophic myotonia patients found structural abnormalities in affected muscles when examined using T1 and STIR imaging. The question remains whether the signs of structural changes in the muscle are merely due to the myotonia, or long-term effects of elevated stress of the tissue, and if so, whether those changes lead to clinically significant loss of contractile properties of the muscle.

This study examines if the contractile properties of myotonic muscles are impaired in MC patients. 40 patients with Thomsens disease (n=20) and Beckers disease (n=20), respectively, will be included along with 20 healthy controls. Peak muscle torque is measured in the hand by hand dynamometer and in the thigh and calf muscles with a Biodex System 4 Pro Dynamometer and the cross-sectional area of the muscles are examined on T1-weighed and Dixon-MRI-scan. With the obtained data peak torque in strength tests, muscle hypertrophy, fat fraction in muscle tissue and contractility of the muscles, compared with healthy controls, will be assessed.

Study Overview

• Status: Completed
• Conditions: Non-Dystrophic Myotonia; Myotonia Congenita

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

• Study Contact: Name: Laura Jacobsen, BSc; Phone Number: +4535456135; Email: laura.noerager.jacobsen.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

40 patients (Thomsens MC, n=20; Beckers MC, n=20) will be included along with 20 healthy age- and gender-matched controls. Inclusion criteria are age >18 years, verified MC diagnosis. Exclusion criteria areknown competing disorders that can interfere with the results (ie. muscular diseases or arthritis) or MRI contraindications.

Before participation patients are asked about medication status. Participants who are treated for their myotonic symptoms with either Mexiletin or Lamotrigin are asked to pause their medication four days prior to participation.

All patients will be asked to evaluate the severity of their myotonic symptoms using the MBS (Myotonic Behaviour Scale) rating from 1 (least severe) to 6 (most severe).

Description

Inclusion Criteria:

• Age <18 years
• Molecularly verified MC (Thomsens or Beckers disease)

Exclusion Criteria:

• Conditions that may impair results of the study, evaluated by the investigator
• Clausphobia
• Pregnancy or breastfeeding
• Metallic objects in and around the body that are not MR-compatible

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
MC; MC patients with either dominant (Thomsens) or recessive (Becker) myotonia.
Healthy Controls; Healthy controls age- and gender matched.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contractile properties	To investigate if contractile properties of the muscles are impaired in MC patients compared with healthy controls.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring muscle hypertrophy in upper and lower limbs	Visualizing and measuring hypertrophy on MRI of affected muscles in the forearm, thigh and calf of MC patients compared with muscles in healthy controls.	1 year

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Heredodegenerative Disorders, Nervous System; Myotonic Disorders; Myotonia; Myotonia Congenita
• Other Study ID Numbers: H-18023049-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No