<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/NCT03037632</url>
  </required_header>
  <id_info>
    <org_study_id>2015H0309</org_study_id>
    <secondary_id>R01HL128857</secondary_id>
    <nct_id>NCT03037632</nct_id>
  </id_info>
  <brief_title>DCM Precision Medicine Study</brief_title>
  <official_title>Precision Medicine for Dilated Cardiomyopathy in European and African Ancestry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ray Hershberger</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Human Genome Research Institute (NHGRI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University</source>
  <oversight_info>
    <has_dmc>Yes</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 aims of the DCM Precision Medicine Study are to test the hypothesis that DCM has&#xD;
      substantial genetic basis and to evaluate the effectiveness of a family communication&#xD;
      intervention in improving the uptake and impact of family member clinical screening.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dilated cardiomyopathy of unknown cause (DCM), known clinically as idiopathic dilated&#xD;
      cardiomypathy, is the most common cardiomyopathy and is the leading cause of heart&#xD;
      transplantation. DCM affects approximately one million individuals, and so has a major impact&#xD;
      on US public health. DCM is commonly asymptomatic until very late in its course when it&#xD;
      causes heart failure, disability, and death. Because of its clinical course, any means to&#xD;
      identify patients at risk for DCM or to detect DCM in its asymptomatic phase could provide&#xD;
      enormous opportunity for intervention to extend lives and prevent late-stage disease. Within&#xD;
      this paradigm precision medicine for DCM could greatly impact health care outcomes and costs.&#xD;
      Recent advances in DCM genetics have introduced these possibilities, but unresolved questions&#xD;
      of familial recurrence risk, genetic etiology, racial differences, and family-based screening&#xD;
      must be addressed to move ahead. The central hypothesis of this study, based on published&#xD;
      studies of the investigative group, states that DCM has substantial genetic basis. For this&#xD;
      study the investigators hypothesize that: (a) 35% of probands of both European and African&#xD;
      ancestry (EA/AA) will be classified as familial in a cohort recruited in a multicenter US&#xD;
      consortium and given explicit recommendations and assistance to achieve the clinical&#xD;
      screening of relatives; (b) approximately 40% of DCM probands, whether categorized as&#xD;
      familial or non-familial, or as EA or AA, will have pathogenic or likely pathogenic variants&#xD;
      in genes previously implicated in DCM; and (c) a tailored intervention to help DCM probands&#xD;
      communicate DCM risk to their family members will improve the uptake and impact of necessary&#xD;
      clinical and genetic testing. To test these hypotheses, the investigators propose to: (1)&#xD;
      estimate and compare the frequencies of EA and AA DCM probands classified as having familial&#xD;
      DCM; (2) estimate and compare the proportions of probands with an identifiable genetic cause&#xD;
      of DCM in groups defined by proband classification (familial/non-familial) and ancestry&#xD;
      (EA/AA); and (3) evaluate the impact of a randomized intervention to aid and direct family&#xD;
      communication on participation of at-risk family members in clinical screening and&#xD;
      appropriate follow-up surveillance for DCM. These aims will be accomplished by recruiting a&#xD;
      cohort of 1300 DCM probands (600 EA, 600 AA, 100 Hispanic ethnicity), performing&#xD;
      cardiovascular clinical screening of 2600 family members, performing genetic testing of&#xD;
      probands and affected family members by exome sequencing, returning genetic results, and&#xD;
      randomizing probands to an intervention to improve family communication regarding DCM risk.&#xD;
      Proving these hypotheses would be transformative for the field: rather than viewing DCM as&#xD;
      only a clinical diagnosis, cardiovascular professionals would understand DCM as a genetic&#xD;
      disease that should be managed using genetic diagnostic and family-based preventive&#xD;
      strategies. These study results would make precision medicine for DCM a reality.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">June 7, 2016</start_date>
  <completion_date type="Anticipated">April 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Blinded until intervention is assigned to subject.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Family clinical screening completed within 12 months from proband enrollment.</measure>
    <time_frame>12 months from proband enrollment.</time_frame>
    <description>The probability that a living first-degree relative (FDR) without a previous definitive DCM diagnosis completes clinical screening for DCM within 12 months after proband recruitment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Living first-degree relative adheres to cardiovascular surveillance recommendations after return of genetic results.</measure>
    <time_frame>2.5 years</time_frame>
    <description>The probability that a living first-degree relative adheres to surveillance recommendations within 15 months after the proband receives individual genetic test information.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">6500</enrollment>
  <condition>Idiopathic Dilated Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Communication Tool</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>No Communication Tool</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Family Heart Talk Booklet</intervention_name>
    <arm_group_label>Communication Tool</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meeting criteria for dilated cardiomyopathy (DCM) :&#xD;
&#xD;
               -  Left ventricular ejection fraction &lt;50%&#xD;
&#xD;
               -  Left ventricular enlargement (A left ventricular end-diastolic dimension &gt;&#xD;
                  95%tile population standard based on gender and height).&#xD;
&#xD;
          -  Detectable causes of cardiomyopathy, except genetic, excluded beyond a reasonable&#xD;
             doubt at the time of DCM diagnosis (that is, meeting clinical criteria for idiopathic&#xD;
             DCM)&#xD;
&#xD;
          -  Any age (including children)&#xD;
&#xD;
          -  Non-Hispanic and Hispanic ethnicity&#xD;
&#xD;
          -  All races (PI pre-approval required for recruitment beyond pre-specified recruitment&#xD;
             targets).&#xD;
&#xD;
          -  Ability to give informed consent&#xD;
&#xD;
          -  Ability to communicate in English (except Spanish language at sites approved to&#xD;
             recruit individuals of Hispanic ethnicity)&#xD;
&#xD;
          -  Willingness to participate in a family-based study (patient willing to work with a&#xD;
             clinical site and/or OSU to facilitate the recruitment and enrollment of family&#xD;
             members to the study).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Coronary artery disease (CAD) causing ischemic cardiomyopathy (&gt; 50% narrowing, any&#xD;
             major epicardial coronary artery)&#xD;
&#xD;
          -  Primary valvular disease&#xD;
&#xD;
          -  Adriamycin or other cardiotoxic drug exposure&#xD;
&#xD;
          -  Other forms of cardiomyopathy: Hypertrophic, Restrictive, or Arrhythmogenic Right&#xD;
             Ventricular Dysplasia/Cardiomyopathy&#xD;
&#xD;
          -  Congenital heart disease&#xD;
&#xD;
          -  Other detectable causes of dilated cardiomyopathy, including sarcoid and&#xD;
             hemochromatosis.&#xD;
&#xD;
          -  Other active multi-system disease that may cause DCM (e.g., active connective tissue&#xD;
             disease).&#xD;
&#xD;
          -  Severe and untreated or untreatable hypertension (systolic blood pressures routinely&#xD;
             greater than 180 mm Hg and/or diastolic blood pressures greater than 120 mm Hg, and if&#xD;
             resistant to multidrug treatment).&#xD;
&#xD;
          -  However, conventional risk factors for DCM, including obesity, routinely treated&#xD;
             hypertension, alcohol use, pregnancy or the peri-partum period, or left ventricular&#xD;
             noncompaction, will NOT be considered exclusion criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ray Hershberger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona Sarver Heart Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medstar Washington Hospital Center (DC)</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Miami Heart Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana State University Health Sciences Center in New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48187</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health Systems</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Heart and Vascular Institute</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://DCMProject.com</url>
    <description>Additional information regarding DCM Precision Medicine Study information provided on website.</description>
  </link>
  <reference>
    <citation>Kinnamon DD, Morales A, Bowen DJ, Burke W, Hershberger RE; DCM Consortium*. Toward Genetics-Driven Early Intervention in Dilated Cardiomyopathy: Design and Implementation of the DCM Precision Medicine Study. Circ Cardiovasc Genet. 2017 Dec;10(6):e001826. doi: 10.1161/CIRCGENETICS.117.001826.</citation>
    <PMID>29237686</PMID>
  </reference>
  <reference>
    <citation>Morales A, Kinnamon DD, Jordan E, Platt J, Vatta M, Dorschner MO, Starkey CA, Mead JO, Ai T, Burke W, Gastier-Foster J, Jarvik GP, Rehm HL, Nickerson DA, Hershberger RE; DCM Precision Medicine study of the DCM Consortium; DCM Consortium institutions and personnel participating in this study: Study Principal Investigator and Co-Investigators,DCM Consortium Clinical Site Principal Investigators and Clinical Site Other Significant Contributors (OSC). The following clinical sites and individuals contributed to the submission of RO 1 H L 128857 as Site Principal Investigators (Site Pl) or as Other Significant Contributors (OSC),Dr. Huggins also served as study co-principal investigator,The following clinical site was added following approval of NHGRI supplemental funding but prior to initiation of enrollment,The following clinical sites were added following study activation. Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study. Circ Genom Precis Med. 2020 Apr;13(2):e002480. doi: 10.1161/CIRCGEN.119.002480. Epub 2020 Mar 11.</citation>
    <PMID>32160020</PMID>
  </reference>
  <reference>
    <citation>Kinnamon DD, Jordan E, Haas GJ, Hofmeyer M, Kransdorf E, Ewald GA, Morris AA, Owens A, Lowes B, Stoller D, Tang WHW, Garg S, Trachtenberg BH, Shah P, Pamboukian SV, Sweitzer NK, Wheeler MT, Wilcox JE, Katz S, Pan S, Jimenez J, Aaronson KD, Fishbein DP, Smart F, Wang J, Gottlieb SS, Judge DP, Moore CK, Mead JO, Huggins GS, Ni H, Burke W, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial. Circulation. 2023 Apr 25;147(17):1281-1290. doi: 10.1161/CIRCULATIONAHA.122.062507. Epub 2023 Mar 20.</citation>
    <PMID>36938756</PMID>
  </reference>
  <reference>
    <citation>Haas GJ, Zareba KM, Ni H, Bello-Pardo E, Huggins GS, Hershberger RE; Study Principal Investigator (PI) and Co-Investigators: The Ohio State University. Validating an Idiopathic Dilated Cardiomyopathy Diagnosis Using Cardiovascular Magnetic Resonance: The Dilated Cardiomyopathy Precision Medicine Study. Circ Heart Fail. 2022 May;15(5):e008877. doi: 10.1161/CIRCHEARTFAILURE.121.008877. Epub 2022 Mar 4.</citation>
    <PMID>35240856</PMID>
  </reference>
  <reference>
    <citation>Huggins GS, Kinnamon DD, Haas GJ, Jordan E, Hofmeyer M, Kransdorf E, Ewald GA, Morris AA, Owens A, Lowes B, Stoller D, Tang WHW, Garg S, Trachtenberg BH, Shah P, Pamboukian SV, Sweitzer NK, Wheeler MT, Wilcox JE, Katz S, Pan S, Jimenez J, Aaronson KD, Fishbein DP, Smart F, Wang J, Gottlieb SS, Judge DP, Moore CK, Mead JO, Ni H, Burke W, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy. JAMA. 2022 Feb 1;327(5):454-463. doi: 10.1001/jama.2021.24674.</citation>
    <PMID>35103767</PMID>
  </reference>
  <reference>
    <citation>Ni H, Jordan E, Cao J, Kinnamon DD, Gottlieb SS, Hofmeyer M, Jimenez J, Judge DP, Kransdorf E, Morris AA, Owens A, Shah P, Tang WHW, Wang J, Hershberger RE. Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy. JAMA Cardiol. 2023 Jan 1;8(1):33-42. doi: 10.1001/jamacardio.2022.4132.</citation>
    <PMID>36383367</PMID>
  </reference>
  <reference>
    <citation>Burke W, Hovick SR, Jordan E, Ni H, Kinnamon DD, Hershberger RE. Communal Coping as a Strategy to Enhance Family Engagement in Dilated Cardiomyopathy. Circ Genom Precis Med. 2022 Jun;15(3):e003541. doi: 10.1161/CIRCGEN.121.003541. Epub 2022 May 10.</citation>
    <PMID>35536229</PMID>
  </reference>
  <reference>
    <citation>Trachtenberg BH, Jimenez J, Morris AA, Kransdorf E, Owens A, Fishbein DP, Jordan E, Kinnamon DD, Mead JO, Huggins GS, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. TTR variants in patients with dilated cardiomyopathy: An investigation of the DCM Precision Medicine Study. Genet Med. 2022 Jul;24(7):1495-1502. doi: 10.1016/j.gim.2022.03.011. Epub 2022 Apr 18.</citation>
    <PMID>35438637</PMID>
  </reference>
  <reference>
    <citation>Hershberger RE, Cowan J, Jordan E, Kinnamon DD. The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy. Circ Res. 2021 May 14;128(10):1514-1532. doi: 10.1161/CIRCRESAHA.121.318157. Epub 2021 May 13.</citation>
    <PMID>33983834</PMID>
  </reference>
  <reference>
    <citation>Hershberger RE. The Evolving Science of Dilated Cardiomyopathy. J Am Coll Cardiol. 2021 Oct 26;78(17):1700-1702. doi: 10.1016/j.jacc.2021.08.038. No abstract available.</citation>
    <PMID>34674814</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>April 8, 2023</last_update_submitted>
  <last_update_submitted_qc>April 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University</investigator_affiliation>
    <investigator_full_name>Ray Hershberger</investigator_full_name>
    <investigator_title>MD</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, Dilated</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/NCT03037632
org study id: 2015H0309
secondary id: R01HL128857
nct id: NCT03037632
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aims of the DCM Precision Medicine Study are to test the hypothesis that DCM has
      substantial genetic basis and to evaluate the effectiveness of a family communication
      intervention in improving the uptake and impact of family member clinical screening.
Dilated cardiomyopathy of unknown cause (DCM), known clinically as idiopathic dilated
      cardiomypathy, is the most common cardiomyopathy and is the leading cause of heart
      transplantation. DCM affects approximately one million individuals, and so has a major impact
      on US public health. DCM is commonly asymptomatic until very late in its course when it
      causes heart failure, disability, and death. Because of its clinical course, any means to
      identify patients at risk for DCM or to detect DCM in its asymptomatic phase could provide
      enormous opportunity for intervention to extend lives and prevent late-stage disease. Within
      this paradigm precision medicine for DCM could greatly impact health care outcomes and costs.
      Recent advances in DCM genetics have introduced these possibilities, but unresolved questions
      of familial recurrence risk, genetic etiology, racial differences, and family-based screening
      must be addressed to move ahead. The central hypothesis of this study, based on published
      studies of the investigative group, states that DCM has substantial genetic basis. For this
      study the investigators hypothesize that: (a) 35% of probands of both European and African
      ancestry (EA/AA) will be classified as familial in a cohort recruited in a multicenter US
      consortium and given explicit recommendations and assistance to achieve the clinical
      screening of relatives; (b) approximately 40% of DCM probands, whether categorized as
      familial or non-familial, or as EA or AA, will have pathogenic or likely pathogenic variants
      in genes previously implicated in DCM; and (c) a tailored intervention to help DCM probands
      communicate DCM risk to their family members will improve the uptake and impact of necessary
      clinical and genetic testing. To test these hypotheses, the investigators propose to: (1)
      estimate and compare the frequencies of EA and AA DCM probands classified as having familial
      DCM; (2) estimate and compare the proportions of probands with an identifiable genetic cause
      of DCM in groups defined by proband classification (familial/non-familial) and ancestry
      (EA/AA); and (3) evaluate the impact of a randomized intervention to aid and direct family
      communication on participation of at-risk family members in clinical screening and
      appropriate follow-up surveillance for DCM. These aims will be accomplished by recruiting a
      cohort of 1300 DCM probands (600 EA, 600 AA, 100 Hispanic ethnicity), performing
      cardiovascular clinical screening of 2600 family members, performing genetic testing of
      probands and affected family members by exome sequencing, returning genetic results, and
      randomizing probands to an intervention to improve family communication regarding DCM risk.
      Proving these hypotheses would be transformative for the field: rather than viewing DCM as
      only a clinical diagnosis, cardiovascular professionals would understand DCM as a genetic
      disease that should be managed using genetic diagnostic and family-based preventive
      strategies. These study results would make precision medicine for DCM a reality.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
masking description: Blinded until intervention is assigned to subject.
measure: Family clinical screening completed within 12 months from proband enrollment.
time frame: 12 months from proband enrollment.
description: The probability that a living first-degree relative (FDR) without a previous definitive DCM diagnosis completes clinical screening for DCM within 12 months after proband recruitment
measure: Living first-degree relative adheres to cardiovascular surveillance recommendations after return of genetic results.
time frame: 2.5 years
description: The probability that a living first-degree relative adheres to surveillance recommendations within 15 months after the proband receives individual genetic test information.
arm group label: Communication Tool
arm group type: Experimental
arm group label: No Communication Tool
arm group type: No Intervention
intervention type: Behavioral
intervention name: Family Heart Talk Booklet
arm group label: Communication Tool
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ray Hershberger, MD
role: Principal Investigator
affiliation: Ohio State University
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country: United States
url: http://DCMProject.com
description: Additional information regarding DCM Precision Medicine Study information provided on website.
citation: Kinnamon DD, Morales A, Bowen DJ, Burke W, Hershberger RE; DCM Consortium*. Toward Genetics-Driven Early Intervention in Dilated Cardiomyopathy: Design and Implementation of the DCM Precision Medicine Study. Circ Cardiovasc Genet. 2017 Dec;10(6):e001826. doi: 10.1161/CIRCGENETICS.117.001826.
PMID: 29237686
citation: Morales A, Kinnamon DD, Jordan E, Platt J, Vatta M, Dorschner MO, Starkey CA, Mead JO, Ai T, Burke W, Gastier-Foster J, Jarvik GP, Rehm HL, Nickerson DA, Hershberger RE; DCM Precision Medicine study of the DCM Consortium; DCM Consortium institutions and personnel participating in this study: Study Principal Investigator and Co-Investigators,DCM Consortium Clinical Site Principal Investigators and Clinical Site Other Significant Contributors (OSC). The following clinical sites and individuals contributed to the submission of RO 1 H L 128857 as Site Principal Investigators (Site Pl) or as Other Significant Contributors (OSC),Dr. Huggins also served as study co-principal investigator,The following clinical site was added following approval of NHGRI supplemental funding but prior to initiation of enrollment,The following clinical sites were added following study activation. Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study. Circ Genom Precis Med. 2020 Apr;13(2):e002480. doi: 10.1161/CIRCGEN.119.002480. Epub 2020 Mar 11.
PMID: 32160020
citation: Kinnamon DD, Jordan E, Haas GJ, Hofmeyer M, Kransdorf E, Ewald GA, Morris AA, Owens A, Lowes B, Stoller D, Tang WHW, Garg S, Trachtenberg BH, Shah P, Pamboukian SV, Sweitzer NK, Wheeler MT, Wilcox JE, Katz S, Pan S, Jimenez J, Aaronson KD, Fishbein DP, Smart F, Wang J, Gottlieb SS, Judge DP, Moore CK, Mead JO, Huggins GS, Ni H, Burke W, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial. Circulation. 2023 Apr 25;147(17):1281-1290. doi: 10.1161/CIRCULATIONAHA.122.062507. Epub 2023 Mar 20.
PMID: 36938756
citation: Haas GJ, Zareba KM, Ni H, Bello-Pardo E, Huggins GS, Hershberger RE; Study Principal Investigator (PI) and Co-Investigators: The Ohio State University. Validating an Idiopathic Dilated Cardiomyopathy Diagnosis Using Cardiovascular Magnetic Resonance: The Dilated Cardiomyopathy Precision Medicine Study. Circ Heart Fail. 2022 May;15(5):e008877. doi: 10.1161/CIRCHEARTFAILURE.121.008877. Epub 2022 Mar 4.
PMID: 35240856
citation: Huggins GS, Kinnamon DD, Haas GJ, Jordan E, Hofmeyer M, Kransdorf E, Ewald GA, Morris AA, Owens A, Lowes B, Stoller D, Tang WHW, Garg S, Trachtenberg BH, Shah P, Pamboukian SV, Sweitzer NK, Wheeler MT, Wilcox JE, Katz S, Pan S, Jimenez J, Aaronson KD, Fishbein DP, Smart F, Wang J, Gottlieb SS, Judge DP, Moore CK, Mead JO, Ni H, Burke W, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy. JAMA. 2022 Feb 1;327(5):454-463. doi: 10.1001/jama.2021.24674.
PMID: 35103767
citation: Ni H, Jordan E, Cao J, Kinnamon DD, Gottlieb SS, Hofmeyer M, Jimenez J, Judge DP, Kransdorf E, Morris AA, Owens A, Shah P, Tang WHW, Wang J, Hershberger RE. Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy. JAMA Cardiol. 2023 Jan 1;8(1):33-42. doi: 10.1001/jamacardio.2022.4132.
PMID: 36383367
citation: Burke W, Hovick SR, Jordan E, Ni H, Kinnamon DD, Hershberger RE. Communal Coping as a Strategy to Enhance Family Engagement in Dilated Cardiomyopathy. Circ Genom Precis Med. 2022 Jun;15(3):e003541. doi: 10.1161/CIRCGEN.121.003541. Epub 2022 May 10.
PMID: 35536229
citation: Trachtenberg BH, Jimenez J, Morris AA, Kransdorf E, Owens A, Fishbein DP, Jordan E, Kinnamon DD, Mead JO, Huggins GS, Hershberger RE; DCM Precision Medicine Study of the DCM Consortium. TTR variants in patients with dilated cardiomyopathy: An investigation of the DCM Precision Medicine Study. Genet Med. 2022 Jul;24(7):1495-1502. doi: 10.1016/j.gim.2022.03.011. Epub 2022 Apr 18.
PMID: 35438637
citation: Hershberger RE, Cowan J, Jordan E, Kinnamon DD. The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy. Circ Res. 2021 May 14;128(10):1514-1532. doi: 10.1161/CIRCRESAHA.121.318157. Epub 2021 May 13.
PMID: 33983834
citation: Hershberger RE. The Evolving Science of Dilated Cardiomyopathy. J Am Coll Cardiol. 2021 Oct 26;78(17):1700-1702. doi: 10.1016/j.jacc.2021.08.038. No abstract available.
PMID: 34674814
responsible party type: Sponsor-Investigator
investigator affiliation: Ohio State University
investigator full name: Ray Hershberger
investigator title: MD
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated
sharing ipd: No