<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/NCT03018184</url>
  </required_header>
  <id_info>
    <org_study_id>H-16045346</org_study_id>
    <nct_id>NCT03018184</nct_id>
  </id_info>
  <brief_title>Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies</brief_title>
  <official_title>Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies Compared to Healthy Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with inherited muscle diseases can have several problems in their muscles, which can&#xD;
      be both structural and metabolic. All the different diseases can affect the contractility of&#xD;
      the muscles. The aim of the study is to investigate the relation between muscle strength and&#xD;
      contractile cross sectional area (CCSA) in the thigh and calf in patients affected by&#xD;
      inherited muscle diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with inherited muscle diseases can have several miscellaneous problems in their&#xD;
      muscles, which can be both structural and metabolic. Depending on the specific disease&#xD;
      multiple symptoms may be present. All the different diseases can affect the contractility of&#xD;
      the muscles. Examples of inherited muscle diseases are congenital myopathies and&#xD;
      RYR1-myopathy, afflicting the muscle fiber structure. They are the first subgroups of&#xD;
      inherited muscle diseases to be investigated in this study. Congenital myopathies are&#xD;
      hereditary and relatively non-progressive diseases. Hypotonia is the clinical characteristic&#xD;
      of congenital myopathies and is often presented already in the neonatal period. Almost all&#xD;
      patients have generalized muscle weakness and hypotonia. The various subtypes of congenital&#xD;
      myopathy are a broad group of disorders defined by the predominance of particular and&#xD;
      specific structural abnormalities shown in muscle biopsies. Based on genetic and&#xD;
      morphological features, they can be divided into four main groups; one with central cores,&#xD;
      one with central nuclei, one with minicores and one with nemaline bodies. RYR1-myopathy is&#xD;
      caused by a mutation in the RYR-gene. The RYR1-protein is important in the making of&#xD;
      RYR1-receptors and channels responsible for the transport of calcium atoms within muscle&#xD;
      cells, particularly in muscle contractions. Patients typically present with limb weakness,&#xD;
      decreased fetal movement and skeletal abnormalities. About 70% of patients with malignant&#xD;
      hyperthermia have a mutation in the RYR1-gene. MRI findings often include involvement of&#xD;
      different muscles in the thigh and the calf.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Muscle CCSA, investigated by Dixon MRI techniques.</measure>
    <time_frame>MRI scan per subject lasts approximately 60 minutes.</time_frame>
    <description>The MRI protocol include a whole body scan. The calf and thigh are chosen for qualitative analysis. Cross sectional area is calculated, the amount of adipose tissue is calculated, and the amount of adipose tissue is subtracted from the CSA, resulting in the CCSA.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Muscle strength, measured as peak torque, investigated by an isokinetic dynamometer (Biodex 4).</measure>
    <time_frame>The tests takes less than an hour per subject.</time_frame>
    <description>The dynamometer makes it possible to isolate particular muscle groups. It is possible to control the range of motion and thereby test in an area free of pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Muscle Strength, MRC</measure>
    <time_frame>The exam lasts less than 15 min per subject.</time_frame>
    <description>Assessment of the muscle strength by a clinical test using &quot;the Medical Research Council Scale for muscle strength&quot; (MRC-scale).</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Inherited Muscle Diseases</condition>
  <condition>Congenital Myopathy</condition>
  <condition>RYR1-myopathy</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRI and Muscle Dynamometer</intervention_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with verified inherited muscle disease.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Verified inherited muscle disease.&#xD;
&#xD;
          -  Age: Over 18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications for an MRI.&#xD;
&#xD;
          -  Claustrophobia.&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
&#xD;
          -  Competing disorders (as arthritis) or other muscle disorders.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Vissing, MD DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Copenhagen Neuromuscular Center, Rigshospitalet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Copenhagen Neuromuscular Center, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Congenital Myopathies: Background, Pathophysiology, Epidemiology [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-overview</citation>
  </reference>
  <reference>
    <citation>Hilton-Jones D, Martin R. Turner. Oxford Textbook of Neuromuscular Disorders. I: Oxford Textbook of Neuromuscular Disorders. Oxford; s. 277-87.</citation>
  </reference>
  <reference>
    <citation>Congenital Myopathies Clinical Presentation: History, Causes [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-clinical</citation>
  </reference>
  <reference>
    <citation>Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, Bittner C, Fialka-Moser V. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 2008 Aug;40(8):665-71. doi: 10.2340/16501977-0235.</citation>
    <PMID>19020701</PMID>
  </reference>
  <reference>
    <citation>Lokken N, Hedermann G, Thomsen C, Vissing J. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I. Ann Neurol. 2016 Sep;80(3):466-71. doi: 10.1002/ana.24743. Epub 2016 Aug 10.</citation>
    <PMID>27463532</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>April 4, 2019</last_update_submitted>
  <last_update_submitted_qc>April 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Anne-Sofie Vibæk Eisum</investigator_full_name>
    <investigator_title>BSc Med.</investigator_title>
  </responsible_party>
  <keyword>MRI</keyword>
  <keyword>CCSA</keyword>
  <keyword>Contractile Cross Sectional Area</keyword>
  <keyword>Strength</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03018184
org study id: H-16045346
nct id: NCT03018184
lead sponsor: 
has dmc: Yes
Patients with inherited muscle diseases can have several problems in their muscles, which can
      be both structural and metabolic. All the different diseases can affect the contractility of
      the muscles. The aim of the study is to investigate the relation between muscle strength and
      contractile cross sectional area (CCSA) in the thigh and calf in patients affected by
      inherited muscle diseases.
Patients with inherited muscle diseases can have several miscellaneous problems in their
      muscles, which can be both structural and metabolic. Depending on the specific disease
      multiple symptoms may be present. All the different diseases can affect the contractility of
      the muscles. Examples of inherited muscle diseases are congenital myopathies and
      RYR1-myopathy, afflicting the muscle fiber structure. They are the first subgroups of
      inherited muscle diseases to be investigated in this study. Congenital myopathies are
      hereditary and relatively non-progressive diseases. Hypotonia is the clinical characteristic
      of congenital myopathies and is often presented already in the neonatal period. Almost all
      patients have generalized muscle weakness and hypotonia. The various subtypes of congenital
      myopathy are a broad group of disorders defined by the predominance of particular and
      specific structural abnormalities shown in muscle biopsies. Based on genetic and
      morphological features, they can be divided into four main groups; one with central cores,
      one with central nuclei, one with minicores and one with nemaline bodies. RYR1-myopathy is
      caused by a mutation in the RYR-gene. The RYR1-protein is important in the making of
      RYR1-receptors and channels responsible for the transport of calcium atoms within muscle
      cells, particularly in muscle contractions. Patients typically present with limb weakness,
      decreased fetal movement and skeletal abnormalities. About 70% of patients with malignant
      hyperthermia have a mutation in the RYR1-gene. MRI findings often include involvement of
      different muscles in the thigh and the calf.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Muscle CCSA, investigated by Dixon MRI techniques.
time frame: MRI scan per subject lasts approximately 60 minutes.
description: The MRI protocol include a whole body scan. The calf and thigh are chosen for qualitative analysis. Cross sectional area is calculated, the amount of adipose tissue is calculated, and the amount of adipose tissue is subtracted from the CSA, resulting in the CCSA.
measure: Muscle strength, measured as peak torque, investigated by an isokinetic dynamometer (Biodex 4).
time frame: The tests takes less than an hour per subject.
description: The dynamometer makes it possible to isolate particular muscle groups. It is possible to control the range of motion and thereby test in an area free of pain.
measure: Muscle Strength, MRC
time frame: The exam lasts less than 15 min per subject.
description: Assessment of the muscle strength by a clinical test using "the Medical Research Council Scale for muscle strength" (MRC-scale).
intervention type: Other
intervention name: MRI and Muscle Dynamometer
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: John Vissing, MD DMSc
role: Principal Investigator
affiliation: Copenhagen Neuromuscular Center, Rigshospitalet
facility: 
country: Denmark
citation: Congenital Myopathies: Background, Pathophysiology, Epidemiology [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-overview
citation: Hilton-Jones D, Martin R. Turner. Oxford Textbook of Neuromuscular Disorders. I: Oxford Textbook of Neuromuscular Disorders. Oxford; s. 277-87.
citation: Congenital Myopathies Clinical Presentation: History, Causes [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-clinical
citation: Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, Bittner C, Fialka-Moser V. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 2008 Aug;40(8):665-71. doi: 10.2340/16501977-0235.
PMID: 19020701
citation: Lokken N, Hedermann G, Thomsen C, Vissing J. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I. Ann Neurol. 2016 Sep;80(3):466-71. doi: 10.1002/ana.24743. Epub 2016 Aug 10.
PMID: 27463532
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Anne-Sofie Vibæk Eisum
investigator title: BSc Med.
mesh term: Muscular Diseases
sharing ipd: No