<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04411732</url>
  </required_header>
  <id_info>
    <org_study_id>Version: 1 [01-JUL-2019]</org_study_id>
    <nct_id>NCT04411732</nct_id>
  </id_info>
  <brief_title>Myotonia and Muscle Stiffness in NMD</brief_title>
  <official_title>Myotonia, Muscle Stiffness and Elasticity in Neuromuscular Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LMU Klinikum</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LMU Klinikum</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess stiffness, muscle tone, relaxation periods&#xD;
      and elasticity of various muscles in patients with dystrophic or non-dystrophic myotonia. The&#xD;
      secondary objectives are (1) to provide reference values for stiffness, muscle tone,&#xD;
      relaxation periods and elasticity of various muscles in patients with dystrophic or&#xD;
      non-dystrophic myotonia; to provide reference values for stiffness, muscle tone, relaxation&#xD;
      periods and elasticity of various muscles in patients with non-myotonic neuromuscular&#xD;
      disorders, (3) assess correlations between to compare result values for stiffness, muscle&#xD;
      tone, relaxation periods and elasticity with clinical muscle function tests, measured by&#xD;
      clinical evaluation (MRC-scale) and the 6-minute walk test; (4) assess correlations between&#xD;
      subcutaneous fat and muscle thickness and echogenicity, measured by muscle ultrasound and&#xD;
      result values for stiffness, muscle tone, relaxation periods and elasticity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>MyotonPro device in patients with dystrophic and non-dystrophic myotonia</measure>
    <time_frame>1 day</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MyotonPro device - reference values in patients with dystrophic and non-dystrophic myotonia</measure>
    <time_frame>1 day</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MyotonPro device - reference values in patients with non-myotonic neuromuscular disorders</measure>
    <time_frame>1 day</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with clinical muscle function tests</measure>
    <time_frame>1 day</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with subcutaneous fat and muscle thickness and echogenicity</measure>
    <time_frame>1 day</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity and the 6-minute-walk test</measure>
    <time_frame>1 day</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Neuromuscular Disorders</condition>
  <arm_group>
    <arm_group_label>patients with neuromuscular disorder</arm_group_label>
    <description>cohort of patients with neuromuscular disorder</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy controls</arm_group_label>
    <description>cohort of healthy controls</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MyotonPro</intervention_name>
    <description>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.</description>
    <arm_group_label>healthy controls</arm_group_label>
    <arm_group_label>patients with neuromuscular disorder</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Six-minute walk test</intervention_name>
    <description>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.</description>
    <arm_group_label>healthy controls</arm_group_label>
    <arm_group_label>patients with neuromuscular disorder</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Semiquantitative muscle ultrasound</intervention_name>
    <description>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.</description>
    <arm_group_label>healthy controls</arm_group_label>
    <arm_group_label>patients with neuromuscular disorder</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Hand-held Dynamometry of muscle strength</intervention_name>
    <description>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.</description>
    <arm_group_label>healthy controls</arm_group_label>
    <arm_group_label>patients with neuromuscular disorder</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Approximately 70 patients will be enrolled, about 3-5 each in the following disease groups:&#xD;
        Limb-Girdle-Muscular Dystrophy (LGMD), Myotonic Dystrophies Type 1 and 2 (DM1, DM2),&#xD;
        Late-Onset-Pompe Disease (LOPD), Distal Myopathies, Congenital Myotonia, Spinal muscular&#xD;
        atrophy Type 3 (SMA3), Amyotrophic lateral sclerosis (ALS) and peripheral Polyneuropathies&#xD;
        (CIDP, HMSN). 20 healthy age- and gender-matched patients will be enrolled as a control&#xD;
        group.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For Patients:&#xD;
&#xD;
          -  ≥18 years of age&#xD;
&#xD;
          -  Confirmed neuromuscular disease&#xD;
&#xD;
          -  written consent&#xD;
&#xD;
          -  able and willing to perform study prodcedures&#xD;
&#xD;
        For healthy volunteers:&#xD;
&#xD;
          -  age ≥18 years of age&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  no clinical sign for neuromuscular disorders&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe comorbidities&#xD;
&#xD;
          -  Patient is participating in another clinical study using investigational treatment&#xD;
&#xD;
          -  Patient cannot perform required muscle function tests&#xD;
&#xD;
          -  the patient, in the opinion of the investigator, is unable to adhere to the&#xD;
             requirements of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Stephan Wenninger, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neurologist</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>LMU Klinikum</investigator_affiliation>
    <investigator_full_name>Prof. Dr. Benedikt Schoser</investigator_full_name>
    <investigator_title>Prof. Dr. med. Benedikt Schoser</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuromuscular Diseases</mesh_term>
    <mesh_term>Myotonia</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT04411732/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04411732
org study id: Version: 1 [01-JUL-2019]
nct id: NCT04411732
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Case-Control
time perspective: Prospective
measure: MyotonPro device in patients with dystrophic and non-dystrophic myotonia
time frame: 1 day
description: 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.
measure: MyotonPro device - reference values in patients with dystrophic and non-dystrophic myotonia
time frame: 1 day
description: 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.
measure: MyotonPro device - reference values in patients with non-myotonic neuromuscular disorders
time frame: 1 day
description: 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.
measure: MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with clinical muscle function tests
time frame: 1 day
description: 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).
measure: MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity with subcutaneous fat and muscle thickness and echogenicity
time frame: 1 day
description: 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.
measure: MyotonPro device - correlations between stiffness, muscle tone, relaxation periods and elasticity and the 6-minute-walk test
time frame: 1 day
description: 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.
arm group label: patients with neuromuscular disorder
description: cohort of patients with neuromuscular disorder
arm group label: healthy controls
description: cohort of healthy controls
intervention type: Device
intervention name: MyotonPro
description: 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.
arm group label: healthy controls
arm group label: patients with neuromuscular disorder
intervention type: Diagnostic Test
intervention name: Six-minute walk test
description: 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.
arm group label: healthy controls
arm group label: patients with neuromuscular disorder
intervention type: Diagnostic Test
intervention name: Semiquantitative muscle ultrasound
description: 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.
arm group label: healthy controls
arm group label: patients with neuromuscular disorder
intervention type: Diagnostic Test
intervention name: Hand-held Dynamometry of muscle strength
description: 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.
arm group label: healthy controls
arm group label: patients with neuromuscular disorder
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Stephan Wenninger, Dr. med.
role: Principal Investigator
affiliation: Neurologist
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: LMU Klinikum
investigator full name: Prof. Dr. Benedikt Schoser
investigator title: Prof. Dr. med. Benedikt Schoser
mesh term: Neuromuscular Diseases
mesh term: Myotonia
provided document: 