Myotonia and Muscle Stiffness in NMD

Study Overview
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Brief Summary
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The primary objective of this study is to assess stiffness, muscle tone, relaxation periods and elasticity of various muscles in patients with dystrophic or non-dystrophic myotonia. The secondary objectives are (1) to provide reference values for stiffness, muscle tone, relaxation periods and elasticity of various muscles in patients with dystrophic or non-dystrophic myotonia; to provide reference values for stiffness, muscle tone, relaxation periods and elasticity of various muscles in patients with non-myotonic neuromuscular disorders, (3) assess correlations between to compare result values for stiffness, muscle tone, relaxation periods and elasticity with clinical muscle function tests, measured by clinical evaluation (MRC-scale) and the 6-minute walk test; (4) assess correlations between subcutaneous fat and muscle thickness and echogenicity, measured by muscle ultrasound and result values for stiffness, muscle tone, relaxation periods and elasticity.

Official Title
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Myotonia, Muscle Stiffness and Elasticity in Neuromuscular Disorders

Conditions
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Neuromuscular Disorders

Intervention / Treatment
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* Device: MyotonPro
* Diagnostic Test: Six-minute walk test
* Diagnostic Test: Semiquantitative muscle ultrasound
* Diagnostic Test: Hand-held Dynamometry of muscle strength


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Patients: ≥18 years of age Confirmed neuromuscular disease written consent able and willing to perform study prodcedures For healthy volunteers: age ≥18 years of age written informed consent no clinical sign for neuromuscular disorders Exclusion Criteria: Severe comorbidities Patient is participating in another clinical study using investigational treatment Patient cannot perform required muscle function tests the patient, in the opinion of the investigator, is unable to adhere to the requirements of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with neuromuscular disorder<br>cohort of patients with neuromuscular disorder | Device: MyotonPro<br>* Measurement of relaxation time, stiffness and elasticity of the following muscles, using the MyotonPro® device: on both sides thenar and hypothenar, m. biceps brachii, m. triceps brachii, m. deltoideus, m. quadriceps femoris, m. tibialis anterior and gastrocnemius muscles.<br>Diagnostic Test: Six-minute walk test<br>* The six-minute walk test (6MWT) measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. The 6MWT has been used with a variety of other conditions than the chronic obstructive pulmonary disease (COPD) such as heart failure and stroke and is widely used in neuromuscular diseases. The six-minute-walk-test will be conducted as recommended by the American Thoracic Society. In this study, the six-minute-walk test will be performed once on visit 1 to detect the impact of muscle weakness, muscle stiffness and myotonia on muscular endurance.<br>Diagnostic Test: Semiquantitative muscle ultrasound<br>* Muscle ultrasound is an ideal imaging modality that allows for atraumatic, noninvasive, radiation-free point-of-care neuromuscular imaging. Muscular dystrophies are typically associated with an increase in the echogenicity from the muscle substance, distal attenuation of muscle echo and a corresponding loss of bone echo. Spinal muscular atrophies and neuropathies also showed an increase in muscle echo along with atrophy of the muscle and increase in depth of subcutaneous tissue, but a persisting bone echo. In several other myopathies, similar changes are seen. In semi-quantitative muscle ultrasound, muscle intensity will be documented using the 4-point Heckmatt score. In addition to that, cutis, subcutaneus fat and muscle will be measured in mm.<br>Diagnostic Test: Hand-held Dynamometry of muscle strength<br>* Muscle strength will be assessed by handheld dynamometry using the MicroFET2 myometer, produced by Hoggan Health Industries. This test is widely used in patients with neuromuscular diseases. To perform a test, the examiner holds the dynamometer stationary while the patient exerts a maximal force against the dynamometer. The patient makes a gradual increase in force and then completes an isometric hold for 4-5 seconds. The following muscle groups will be tested: Arm abduction, elbow flexion, elbow extension, knee extension, knee flexion, foot extension, foot flexion.<br>|
| healthy controls<br>cohort of healthy controls | Device: MyotonPro<br>* Measurement of relaxation time, stiffness and elasticity of the following muscles, using the MyotonPro® device: on both sides thenar and hypothenar, m. biceps brachii, m. triceps brachii, m. deltoideus, m. quadriceps femoris, m. tibialis anterior and gastrocnemius muscles.<br>Diagnostic Test: Six-minute walk test<br>* The six-minute walk test (6MWT) measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. The 6MWT has been used with a variety of other conditions than the chronic obstructive pulmonary disease (COPD) such as heart failure and stroke and is widely used in neuromuscular diseases. The six-minute-walk-test will be conducted as recommended by the American Thoracic Society. In this study, the six-minute-walk test will be performed once on visit 1 to detect the impact of muscle weakness, muscle stiffness and myotonia on muscular endurance.<br>Diagnostic Test: Semiquantitative muscle ultrasound<br>* Muscle ultrasound is an ideal imaging modality that allows for atraumatic, noninvasive, radiation-free point-of-care neuromuscular imaging. Muscular dystrophies are typically associated with an increase in the echogenicity from the muscle substance, distal attenuation of muscle echo and a corresponding loss of bone echo. Spinal muscular atrophies and neuropathies also showed an increase in muscle echo along with atrophy of the muscle and increase in depth of subcutaneous tissue, but a persisting bone echo. In several other myopathies, similar changes are seen. In semi-quantitative muscle ultrasound, muscle intensity will be documented using the 4-point Heckmatt score. In addition to that, cutis, subcutaneus fat and muscle will be measured in mm.<br>Diagnostic Test: Hand-held Dynamometry of muscle strength<br>* Muscle strength will be assessed by handheld dynamometry using the MicroFET2 myometer, produced by Hoggan Health Industries. This test is widely used in patients with neuromuscular diseases. To perform a test, the examiner holds the dynamometer stationary while the patient exerts a maximal force against the dynamometer. The patient makes a gradual increase in force and then completes an isometric hold for 4-5 seconds. The following muscle groups will be tested: Arm abduction, elbow flexion, elbow extension, knee extension, knee flexion, foot extension, foot flexion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MyotonPro device in patients with dystrophic and non-dystrophic myotonia | The primary objective of this study is the comparison of viscoelastic stiffness of the underlying tissue measured by stiffness (S), elasticity (D) and relaxation (R) between patients with dystrophic and non-dystrophic myotonia. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MyotonPro device - reference values in patients with dystrophic and non-dystrophic myotonia | The secondary objective of this study is to provide reference values for stiffness, muscle tone, relaxation periods and elasticity of various muscles in patients with dystrophic or non-dystrophic myotonia. | 1 day | 
| MyotonPro device - reference values in patients with non-myotonic neuromuscular disorders | The secondary objective of this study is to provide reference values for stiffness, muscle tone, relaxation periods and elasticity of various muscles in patients with non-myotonic neuromuscular disorders. | 1 day | 
| MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with clinical muscle function tests | The secondary objective of this study is to compare stiffness, muscle tone, relaxation periods and elasticity with clinical muscle function tests, measured by clinical evaluation (MRC-scale). | 1 day | 
| MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with subcutaneous fat and muscle thickness and echogenicity | The secondary objective of this study is to assess correlations between subcutaneous fat and muscle thickness and echogenicity, measured by muscle ultrasound and result values for stiffness, muscle tone, relaxation periods and elasticity. | 1 day | 
| MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity and the 6-minute-walk test | The secondary objective of this study is to compare stiffness, muscle tone, relaxation periods and elasticity with clinical muscle endurance function tests, measured by the 6-minute walk test. | 1 day |