DCM Precision Medicine Study

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Brief Title

DCM Precision Medicine Study

Official Title

Precision Medicine for Dilated Cardiomyopathy in European and African Ancestry

Brief Summary

      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.
    

Detailed Description

      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.
    


Study Type

Interventional


Primary Outcome

Family clinical screening completed within 12 months from proband enrollment.


Condition

Idiopathic Dilated Cardiomyopathy

Intervention

Family Heart Talk Booklet

Study Arms / Comparison Groups

 Communication Tool
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Behavioral

Estimated Enrollment

6500

Start Date

June 7, 2016

Completion Date

June 2021

Primary Completion Date

August 1, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Meeting criteria for dilated cardiomyopathy (DCM) :

               -  Left ventricular ejection fraction <50%

               -  Left ventricular enlargement (A left ventricular end-diastolic dimension >
                  95%tile population standard based on gender and height).

          -  Detectable causes of cardiomyopathy, except genetic, excluded beyond a reasonable
             doubt at the time of DCM diagnosis (that is, meeting clinical criteria for idiopathic
             DCM)

          -  Any age (including children)

          -  Non-Hispanic and Hispanic ethnicity

          -  All races (PI pre-approval required for recruitment beyond pre-specified recruitment
             targets).

          -  Ability to give informed consent

          -  Ability to communicate in English (except Spanish language at sites approved to
             recruit individuals of Hispanic ethnicity)

          -  Willingness to participate in a family-based study (patient willing to work with a
             clinical site and/or OSU to facilitate the recruitment and enrollment of family
             members to the study).

        Exclusion Criteria:

          -  Coronary artery disease (CAD) causing ischemic cardiomyopathy (> 50% narrowing, any
             major epicardial coronary artery)

          -  Primary valvular disease

          -  Adriamycin or other cardiotoxic drug exposure

          -  Other forms of cardiomyopathy: Hypertrophic, Restrictive, or Arrhythmogenic Right
             Ventricular Dysplasia/Cardiomyopathy

          -  Congenital heart disease

          -  Other detectable causes of dilated cardiomyopathy, including sarcoid and
             hemochromatosis.

          -  Other active multi-system disease that may cause DCM (e.g., active connective tissue
             disease).

          -  Severe and untreated or untreatable hypertension (systolic blood pressures routinely
             greater than 180 mm Hg and/or diastolic blood pressures greater than 120 mm Hg, and if
             resistant to multidrug treatment).

          -  However, conventional risk factors for DCM, including obesity, routinely treated
             hypertension, alcohol use, pregnancy or the peri-partum period, or left ventricular
             noncompaction, will NOT be considered exclusion criteria.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Ray Hershberger, MD, 614-688-1388, 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03037632

Organization ID

2015H0309

Secondary IDs

R01HL128857

Responsible Party

Sponsor-Investigator

Study Sponsor

Ray Hershberger

Collaborators

 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Ray Hershberger, MD, Principal Investigator, Ohio State University


Verification Date

August 2019