DCM Precision Medicine Study
- Conditions
- Idiopathic Dilated Cardiomyopathy
- Interventions
- Behavioral: Family Heart Talk Booklet
- Registration Number
- NCT03037632
- Lead Sponsor
- Ray Hershberger
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 6500
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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).
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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)
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Any age (including children)
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Non-Hispanic and Hispanic ethnicity
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All races (PI pre-approval required for recruitment beyond pre-specified recruitment targets).
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Ability to give informed consent
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Ability to communicate in English (except Spanish language at sites approved to recruit individuals of Hispanic ethnicity)
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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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Communication Tool Family Heart Talk Booklet -
- Primary Outcome Measures
Name Time Method Family clinical screening completed within 12 months from proband enrollment. 12 months from proband enrollment. 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
Living first-degree relative adheres to cardiovascular surveillance recommendations after return of genetic results. 2.5 years The probability that a living first-degree relative adheres to surveillance recommendations within 15 months after the proband receives individual genetic test information.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (26)
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Inova Heart and Vascular Institute
🇺🇸Fairfax, Virginia, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
South Miami Heart Center
🇺🇸Miami, Florida, United States
University of Arizona Sarver Heart Center
🇺🇸Tucson, Arizona, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Medstar Washington Hospital Center (DC)
🇺🇸Washington, District of Columbia, United States
NYU School of Medicine
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Cedars-Sinai Medical Center
🇺🇸Beverly Hills, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Louisiana State University Health Sciences Center in New Orleans
🇺🇸New Orleans, Louisiana, United States