<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/NCT03043209</url>
  </required_header>
  <id_info>
    <org_study_id>17-090</org_study_id>
    <nct_id>NCT03043209</nct_id>
  </id_info>
  <brief_title>Genomic Sequencing in Patients With HCM Undergoing Septal Myectomy</brief_title>
  <official_title>Genomic Sequencing in Patients With Hypertrophic Cardiomyopathy Undergoing Septal Myectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</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>
      Investigators aim to use comparative exome and/or genome sequencing to discover causative&#xD;
      molecular lesions for phenotypes hypothesized to be caused by somatic mutations. For this&#xD;
      study, investigators have targeted hypertrophic cardiomyopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The hypothesis is that sporadic or simplex occurrences of what are typically autosomal&#xD;
      dominantly inherited diseases can instead be caused my mosaic mutations, specifically,&#xD;
      mutations in the heart itself.&#xD;
&#xD;
      This hypothesis mandates that investigators sequence both affected and unaffected tissues,&#xD;
      which in this case, investigators will construe to be peripheral blood DNA and discarded&#xD;
      myocardium from cardiac procedures.&#xD;
&#xD;
      Eligible individuals will first undergo informed consent to be part of the study prior to&#xD;
      their scheduled myomectomy. The study participants will also have phlebotomy for research&#xD;
      samples.&#xD;
&#xD;
      The NIH Intramural Sequencing Center (NISC) will perform paired exome or genome sequencing&#xD;
      and we will first screen for germline mutations in known cardiomyopathy genes that meet ACMG&#xD;
      standards of likely pathogenic or pathogenic.&#xD;
&#xD;
      Then, if this is negative, investigators will screen for sequence variants that are present&#xD;
      in cardiac tissue but absent in the blood DNA. Investigators will also screen blood DNA for&#xD;
      secondary findings in genes recommended for annotation and results return by the ACMG and&#xD;
      sequence variants deemed clinically relevant in this gene set will be validated in a&#xD;
      CLIA-certified laboratory and the results returned to that participant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2018</start_date>
  <completion_date type="Actual">December 28, 2022</completion_date>
  <primary_completion_date type="Actual">December 4, 2020</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Genetic causes of HCM in patients without a strong family history of the condition</measure>
    <time_frame>one year</time_frame>
    <description>The investigators will use DNA testing technology called &quot;genomic sequencing&quot;</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Hypertrophic Cardiomyopathy</condition>
  <condition>Genetic Disease</condition>
  <condition>Gene Product Sequence Variation</condition>
  <arm_group>
    <arm_group_label>Genomic sequencing</arm_group_label>
    <description>Perform Genomic sequencing in peripheral blood DNA and discarded myocardium from cardiac procedures</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Genomic sequencing</intervention_name>
    <description>Genomic sequencing of DNA in Blood sample and myectomy tissue</description>
    <arm_group_label>Genomic sequencing</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      leftover of myectomy tissue and peripheral blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        18 years and older, scheduled for septal myectomy and no family history of HCM&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient is 18 years and older has a clinical diagnosis of hypertrophic cardiomyopathy.&#xD;
&#xD;
          -  Patient scheduled for clinically-indicated myomectomy.&#xD;
&#xD;
          -  Patient has a negative family history of hypertrophic cardiomyopathy&#xD;
&#xD;
          -  Patient is willing to receive results of secondary variant screen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Milind Desai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>January 4, 2023</last_update_submitted>
  <last_update_submitted_qc>January 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Milind Desai</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Hypertrophic</mesh_term>
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03043209
org study id: 17-090
nct id: NCT03043209
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Investigators aim to use comparative exome and/or genome sequencing to discover causative
      molecular lesions for phenotypes hypothesized to be caused by somatic mutations. For this
      study, investigators have targeted hypertrophic cardiomyopathy.
The hypothesis is that sporadic or simplex occurrences of what are typically autosomal
      dominantly inherited diseases can instead be caused my mosaic mutations, specifically,
      mutations in the heart itself.

      This hypothesis mandates that investigators sequence both affected and unaffected tissues,
      which in this case, investigators will construe to be peripheral blood DNA and discarded
      myocardium from cardiac procedures.

      Eligible individuals will first undergo informed consent to be part of the study prior to
      their scheduled myomectomy. The study participants will also have phlebotomy for research
      samples.

      The NIH Intramural Sequencing Center (NISC) will perform paired exome or genome sequencing
      and we will first screen for germline mutations in known cardiomyopathy genes that meet ACMG
      standards of likely pathogenic or pathogenic.

      Then, if this is negative, investigators will screen for sequence variants that are present
      in cardiac tissue but absent in the blood DNA. Investigators will also screen blood DNA for
      secondary findings in genes recommended for annotation and results return by the ACMG and
      sequence variants deemed clinically relevant in this gene set will be validated in a
      CLIA-certified laboratory and the results returned to that participant.
observational model: Case-Only
time perspective: Prospective
measure: Genetic causes of HCM in patients without a strong family history of the condition
time frame: one year
description: The investigators will use DNA testing technology called "genomic sequencing"
arm group label: Genomic sequencing
description: Perform Genomic sequencing in peripheral blood DNA and discarded myocardium from cardiac procedures
intervention type: Genetic
intervention name: Genomic sequencing
description: Genomic sequencing of DNA in Blood sample and myectomy tissue
arm group label: Genomic sequencing
leftover of myectomy tissue and peripheral blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Milind Desai, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Milind Desai
investigator title: Medical Doctor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Hypertrophic
mesh term: Genetic Diseases, Inborn
mesh term: Hypertrophy
sharing ipd: Undecided