Muscle Relaxation in Myopathies With Positive Muscle Phenomena

NCT03211923 | Unknown DMC

• 1 other identifier: NL57301.091.16
• Study Type: observational
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to quantify muscle relaxation properties of the finger flexor muscles in patients with different myopathies. The inhibiting effects of transcranial magnetic stimulation (TMS) on the cortical motor hand area are used to induce relaxation, which in turn will be monitored with handgrip dynamometry and EMG. The investigators will evaluate if this technique can be implemented as a diagnostic tool in clinical practice. Muscle relaxation is an often overlooked property of the muscle as compared to muscle strength or activation. Muscle relaxation is affected in different myopathies, such as myotonic dystrophy, non-dystrophic myotonias, and Brody myopathy. Therefore, a diagnostic tool to quantify muscle relaxation is of clinical and scientific importance. In this study, transcranial magnetic stimulation (TMS) is used, in combination with a dynamometer to quantify muscle relaxation properties. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is commonly used to stimulate the brain. In practice, a circular coil is held directly above the scalp, upon which a strong current pulse induces a magnetic field that stimulates the underlying superficial brain areas. This stimulation can have both activating and inhibiting effects. When the motor cortex (i.e. the area of the brain that controls muscle contractions) is strongly stimulated with TMS during a voluntary muscle contraction, both excitatory and inhibitory effects can be observed in the muscle the targeted cortical area controls. The inhibitory effect entails a transient interruption of neural drive to the muscle. This interruption, called the "silent period", lasts for less than half a second and results in the relaxation of the muscle. Muscle activity and control quickly return to normal after the silent period. The elegance and main advantage of TMS-induced muscle relaxation lies in the fact that it excludes all voluntary influences on the relaxation process. Furthermore, the TMS pulse causes all muscle fibres involved in the contraction just prior to the onset of the silent period to relax simultaneously. This allows us to study muscle relaxation as only a property of the muscle, i.e. without voluntary influences. In this study, the investigators will measure muscle relaxation in several myopathies (McArdle disease, Nemaline myopathy type 6 and myotonic dystrophy type 2) and compare this to healthy controls and to controls with no myopathy but with similar complaints (myalgia, stiffness, cramps). The data from these two control groups has been gathered previously in a different study. The investigators will also compare this to patients suffering from Brody disease who were previously measured in a different study. Muscle relaxation will be evaluated in fresh and fatigued finger flexor muscles. The main outcome of this study is the peak relaxation rate normalized to the peak force preceding relaxation. The final outlook of this research is to evaluate whether muscle relaxation studied with TMS, can be used for different myopathies as a diagnostic tool, to monitor disease progression, and to study the effects of different interventions (e.g. medication, exercise).

Conditions

Nemaline Myopathy Type 6; Myotonic Dystrophy Type 2; McArdle Disease

Keywords

muscle relaxation; transcranial magnetic stimulation; myopathy

Outcome Measures

Primary Outcomes (1)

• Normalized peak relaxation rate

  Maximal rate at which the muscle relaxes after the TMS pulse, defined as the steepest point on the force curve. This value is normalised to the force that preceded relaxation, i.e. top of the superimposed twitch.

  1 hour

Secondary Outcomes (3)

• Force decline at 150ms

  1 hour

• Relaxation times (RT)

  1 hour

• Maximal muscle strength

  1 hour

Study Arms (6)

Nemaline myopathy type 6 (NEM6)

Patients diagnosed with nemaline myopathy type 6 (mutation in KBTBD13 gene). The aim is to measure five male and five female patients.

Diagnostic Test: Transcranial magnetic stimulation (TMS)

Myotonic dystrophy type 2 (DM2)

Patients diagnosed with myotonic dystrophy type 2 (pathological repeat expansion in CNBP gene). The aim is to measure five male and five female patients.

Diagnostic Test: Transcranial magnetic stimulation (TMS)

McArdle disease (McA)

Patients diagnosed with McArdle disease (mutation in PYGM gene). The aim is to measure five male and five female patients.

Diagnostic Test: Transcranial magnetic stimulation (TMS)

Healthy controls

14 male and 10 female healthy subjects were measured in a previous study

Controls with positive muscle phenomena

9 male and 8 female subjects with positive muscle phenomena but no myopathy, ruled out by normal muscle biopsy, CK level, and genetic testing. These subjects were measured in a previous study.

Brody disease

4 male patients diagnosed with Brody disease (ATP2A1 mutation). All Dutch patients suffering from Brody disease (n=4) were measured in a previous study

Interventions

Transcranial magnetic stimulation (TMS) DIAGNOSTIC_TEST

Single pulse, monophasic transcranial magnetic stimulation

McArdle disease (McA); Myotonic dystrophy type 2 (DM2); Nemaline myopathy type 6 (NEM6)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease. Patients will be selected from a local database at the Radboud University Medical Center. The goal is to include 5 men and 5 women per myopathy.

You may qualify if:

• \- Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease.

You may not qualify if:

• Pregnancy
• Serious head trauma or brain surgery
• Large or ferromagnetic metal parts in the head
• Implanted cardiac pacemaker or neurostimulator
• Epilepsy, convulsion or seizure
• Use of medication that can influence muscle relaxation or cortical excitability

Sponsors & Collaborators

• Radboud University Medical Center: lead

MeSH Terms

Conditions

Myotonic Dystrophy; Glycogen Storage Disease Type V; Muscular Diseases

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Baziel G van Engelen, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 7, 2017
• Study Start: January 5, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: October 1, 2019

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share