<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/NCT02972580</url>
  </required_header>
  <id_info>
    <org_study_id>IRB16-00319</org_study_id>
    <nct_id>NCT02972580</nct_id>
  </id_info>
  <brief_title>Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD</brief_title>
  <official_title>Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parent Project Muscular Dystrophy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Longitudinal prospective observational study. This is a 24-month study with the possibility&#xD;
      of extending the data time points. Initially baseline, then 12 and 24 months follow up&#xD;
      studies will be completed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Four cohorts are enrolled in this study. The target population is the cohort of genetically&#xD;
      confirmed DMD/BMD female carriers (Cohort A). This cohort will consist of 150 DMD/BMD mothers&#xD;
      who are somatic carriers of a mutation in the DMD gene. The data collected for this cohort&#xD;
      will be compared to three control groups; Control Group B is a cohort of 50 DMD/BMD mothers&#xD;
      who are NOT somatic carriers, Control Group C is a cohort of 50 age-matched healthy controls&#xD;
      and Control Group D is a cohort of 25 genetically confirmed carriers who do not have an&#xD;
      affected child. The inclusion of a Control Group B allows for a comparison to a group of&#xD;
      mothers that share the emotional and cognitive burden of caring for an affected male without&#xD;
      having the physical or cognitive risks of being a female carrier. The Control Group C offers&#xD;
      robust data from an age-matched healthy cohort for purposes of comparison. Control Group D&#xD;
      allows for comparison to a group of women that have the same physical or cognitive risks as&#xD;
      the Cohort A female carriers, but do not have the same burden of care giving.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>June 2016</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging</measure>
    <time_frame>2 years</time_frame>
    <description>Cardiac function as compromised by evidence of scarring of cardiac muscles, particularly of the base of the left ventricle via cardiac MRI studies with gadolinium contrast.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiac Function Assessment Treadmill SVO2</measure>
    <time_frame>2 years</time_frame>
    <description>Stress on heart muscle measured by SVO2 (percentage of oxygen saturation in the blood of the pulmonary artery). SVO2 represents an average of all the venous oxygen saturation of major organs and tissues. This measure provides assessment of cardiopulmonary function and helps measure the degree of cardiac instability and can be an indicator of deterioration from normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing</measure>
    <time_frame>2 Years</time_frame>
    <description>MVICT measures strength of skeletal muscles by assessing the force generated by by individual muscles. The results can be compared to norms and deterioration can be assessed over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Therapy Assessments 6 Minute Walk Test</measure>
    <time_frame>2 years</time_frame>
    <description>A timed test to assess distance walked in 6 minutes is very quantitative and can be assessed in comparison to normal controls. Deterioration over time can be clearly measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Therapy Assessments ACTIVE-seated</measure>
    <time_frame>2 Years</time_frame>
    <description>Exploratory outcome quantifying upper extremity reaching ability using a custom-designed game telling how far the arm reaches in comparison to overall functional ability of the individual ability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Therapy Assessments Time-to-Rise</measure>
    <time_frame>2 Years</time_frame>
    <description>A timed-test to measure ability to rise from the floor is quantifiable and measuring over time tells if there is loss of function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory biomarkers - Creatine Kinase</measure>
    <time_frame>2 Years</time_frame>
    <description>CK levels are an indicator of muscle breakdown.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory biomarkers - C-Reactive Protein</measure>
    <time_frame>2 Years</time_frame>
    <description>Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory biomarkers - Interleukin-6</measure>
    <time_frame>2 Years</time_frame>
    <description>Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory biomarkers - Cortisol levels</measure>
    <time_frame>2 Years</time_frame>
    <description>Hair cortisol levels measure stress levels as a means of understanding coping with disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Assessment</measure>
    <time_frame>2 Years</time_frame>
    <description>Cognitive function measured by Wechsler Abbreviated Scale of Intelligence (WASI) provides a possible tool to measure disease awareness and establish if IQ level correlates with disease-related stress.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Stress</measure>
    <time_frame>2 Years</time_frame>
    <description>Online self-report survey to assess stress burden on caregiver.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function testing (PFTs)</measure>
    <time_frame>2 Years</time_frame>
    <description>Stable or improved FVC</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Duchenne Muscular Dystrophy</condition>
  <condition>Becker Muscular Dystrophy</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <description>DMD/BMD Female Carriers who have/had an affected child (n=150)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <description>DMD/BMD Female non-carriers controls who have/had an affected child (n=50)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <description>Healthy Age-Matched Controls (n=50)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <description>DMD/BMD Female Carriers with no affected children (n=25)</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Genetic characterization</intervention_name>
    <description>Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The blood sample for genetic testing will be delivered to the Molecular Genetics lab at&#xD;
      Nationwide Children's Hospital, where genomic DNA will be isolated from peripheral white&#xD;
      blood cells. DNA will be banked frozen while a portion of the sample will be delivered to the&#xD;
      Emory Molecular Genetics Laboratories for testing of the DMD gene.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Cohort A: DMD/BMD Female Carriers who have/had an affected child (n=150) Cohort B: DMD/BMD&#xD;
        Female non-carriers controls who have/had an affected child (n=50) Cohort C: Healthy&#xD;
        Age-Matched Controls (n=50) Cohort D: DMD/BMD Female Carriers who do not have/had an&#xD;
        affected child (n=25)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Cohort A requires a genetically confirmed mutation in the DMD gene with an affected&#xD;
             child&#xD;
&#xD;
          -  Cohort B includes DMD/BMD mothers with NO somatic mutation in the DMD gene&#xD;
&#xD;
          -  Cohort C age-matched healthy controls with a normal CK level&#xD;
&#xD;
          -  Cohort D requires a genetically confirmed mutation in the DMD gene without an affected&#xD;
             child&#xD;
&#xD;
          -  Able to complete testing in English&#xD;
&#xD;
          -  Able to consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a contraindication to cardiac or skeletal muscle MRI&#xD;
&#xD;
          -  Subjects on heart failure medication at time of enrollment&#xD;
&#xD;
          -  Subjects on steroid treatment&#xD;
&#xD;
          -  Presence of an inherited neurologic disease or comorbidity that may affect their&#xD;
             ability to complete this study&#xD;
&#xD;
          -  Has a medical condition or extenuating circumstance that, in the opinion of the&#xD;
             investigator, might compromise the subject's ability to comply with the protocol&#xD;
             required testing or procedures or compromise the subject's wellbeing, safety, or&#xD;
             clinical interpretability&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>May Ling Mah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PI</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kate Kanwar, MS</last_name>
    <phone>614-355-5649</phone>
    <email>Kate.Kanwar@nationwidechildrens.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Victoria Shay, MS</last_name>
    <phone>615-355-5819</phone>
    <email>Victoria.Shay@nationwidechildrens.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nationwide Children's Hosptial</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kate Kanwar, MS</last_name>
      <phone>614-355-5649</phone>
      <email>Kate.kanwar@nationwidechildrens.org</email>
    </contact>
    <contact_backup>
      <last_name>Victoria Shay, MS</last_name>
      <phone>615-355-5819</phone>
      <email>victoria.shay@nationwidechildrens.org</email>
    </contact_backup>
    <investigator>
      <last_name>May Ling Mah, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jerry Mendell, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kan Hor, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Linda Cripe, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jamie Jackson, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lindsay Alfano, DPT</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kelly Lehman, CNP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 25, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>May Ling Mah</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Dystrophies</mesh_term>
    <mesh_term>Muscular Dystrophy, Duchenne</mesh_term>
  </condition_browse>
  <!-- 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/NCT02972580
org study id: IRB16-00319
nct id: NCT02972580
lead sponsor: 
collaborator: 
has dmc: No
Longitudinal prospective observational study. This is a 24-month study with the possibility
      of extending the data time points. Initially baseline, then 12 and 24 months follow up
      studies will be completed.
Four cohorts are enrolled in this study. The target population is the cohort of genetically
      confirmed DMD/BMD female carriers (Cohort A). This cohort will consist of 150 DMD/BMD mothers
      who are somatic carriers of a mutation in the DMD gene. The data collected for this cohort
      will be compared to three control groups; Control Group B is a cohort of 50 DMD/BMD mothers
      who are NOT somatic carriers, Control Group C is a cohort of 50 age-matched healthy controls
      and Control Group D is a cohort of 25 genetically confirmed carriers who do not have an
      affected child. The inclusion of a Control Group B allows for a comparison to a group of
      mothers that share the emotional and cognitive burden of caring for an affected male without
      having the physical or cognitive risks of being a female carrier. The Control Group C offers
      robust data from an age-matched healthy cohort for purposes of comparison. Control Group D
      allows for comparison to a group of women that have the same physical or cognitive risks as
      the Cohort A female carriers, but do not have the same burden of care giving.
observational model: Cohort
time perspective: Prospective
measure: Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging
time frame: 2 years
description: Cardiac function as compromised by evidence of scarring of cardiac muscles, particularly of the base of the left ventricle via cardiac MRI studies with gadolinium contrast.
measure: Cardiac Function Assessment Treadmill SVO2
time frame: 2 years
description: Stress on heart muscle measured by SVO2 (percentage of oxygen saturation in the blood of the pulmonary artery). SVO2 represents an average of all the venous oxygen saturation of major organs and tissues. This measure provides assessment of cardiopulmonary function and helps measure the degree of cardiac instability and can be an indicator of deterioration from normal.
measure: Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing
time frame: 2 Years
description: MVICT measures strength of skeletal muscles by assessing the force generated by by individual muscles. The results can be compared to norms and deterioration can be assessed over time.
measure: Physical Therapy Assessments 6 Minute Walk Test
time frame: 2 years
description: A timed test to assess distance walked in 6 minutes is very quantitative and can be assessed in comparison to normal controls. Deterioration over time can be clearly measured.
measure: Physical Therapy Assessments ACTIVE-seated
time frame: 2 Years
description: Exploratory outcome quantifying upper extremity reaching ability using a custom-designed game telling how far the arm reaches in comparison to overall functional ability of the individual ability.
measure: Physical Therapy Assessments Time-to-Rise
time frame: 2 Years
description: A timed-test to measure ability to rise from the floor is quantifiable and measuring over time tells if there is loss of function.
measure: Laboratory biomarkers - Creatine Kinase
time frame: 2 Years
description: CK levels are an indicator of muscle breakdown.
measure: Laboratory biomarkers - C-Reactive Protein
time frame: 2 Years
description: Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
measure: Laboratory biomarkers - Interleukin-6
time frame: 2 Years
description: Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
measure: Laboratory biomarkers - Cortisol levels
time frame: 2 Years
description: Hair cortisol levels measure stress levels as a means of understanding coping with disease.
measure: Cognitive Assessment
time frame: 2 Years
description: Cognitive function measured by Wechsler Abbreviated Scale of Intelligence (WASI) provides a possible tool to measure disease awareness and establish if IQ level correlates with disease-related stress.
measure: Caregiver Stress
time frame: 2 Years
description: Online self-report survey to assess stress burden on caregiver.
measure: Pulmonary function testing (PFTs)
time frame: 2 Years
description: Stable or improved FVC
arm group label: Cohort A
description: DMD/BMD Female Carriers who have/had an affected child (n=150)
arm group label: Cohort B
description: DMD/BMD Female non-carriers controls who have/had an affected child (n=50)
arm group label: Cohort C
description: Healthy Age-Matched Controls (n=50)
arm group label: Cohort D
description: DMD/BMD Female Carriers with no affected children (n=25)
intervention type: Genetic
intervention name: Genetic characterization
description: Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
The blood sample for genetic testing will be delivered to the Molecular Genetics lab at
      Nationwide Children's Hospital, where genomic DNA will be isolated from peripheral white
      blood cells. DNA will be banked frozen while a portion of the sample will be delivered to the
      Emory Molecular Genetics Laboratories for testing of the DMD gene.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: May Ling Mah, MD
role: Principal Investigator
affiliation: PI
last name: Kate Kanwar, MS
phone: 614-355-5649
email: Kate.Kanwar@nationwidechildrens.org
last name: Victoria Shay, MS
phone: 615-355-5819
email: Victoria.Shay@nationwidechildrens.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: May Ling Mah
investigator title: Principal Investigator
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne