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DCM Precision Medicine Study

Sponsor
Ray Hershberger (Other)
Overall Status
Recruiting
CT.gov ID
NCT03037632
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Human Genome Research Institute (NHGRI) (NIH)
6,500
Enrollment
27
Locations
2
Arms
70.7
Anticipated Duration (Months)
240.7
Patients Per Site
3.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Behavioral: Family Heart Talk Booklet
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
6500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Blinded until intervention is assigned to subject.
Primary Purpose:
Prevention
Official Title:
Precision Medicine for Dilated Cardiomyopathy in European and African Ancestry
Actual Study Start Date :
Jun 7, 2016
Anticipated Primary Completion Date :
Apr 30, 2022
Anticipated Study Completion Date :
Apr 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Communication Tool

Behavioral: Family Heart Talk Booklet
No Intervention: No Communication Tool

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham Birmingham Alabama United States 35294
2 University of Arizona Sarver Heart Center Tucson Arizona United States 85724
3 Cedars-Sinai Medical Center Beverly Hills California United States 90211
4 UCLA Medical Center Los Angeles California United States 90095
5 Stanford University Palo Alto California United States 94304
6 Medstar Washington Hospital Center (DC) Washington District of Columbia United States 20010
7 South Miami Heart Center Miami Florida United States 33143
8 Emory University Atlanta Georgia United States 30322
9 Northwestern University Chicago Illinois United States 60611
10 Louisiana State University Health Sciences Center in New Orleans New Orleans Louisiana United States 70112
11 University of Maryland Baltimore Maryland United States 21201
12 Tufts Medical Center Boston Massachusetts United States 02111
13 University of Michigan Ann Arbor Michigan United States 48187
14 Henry Ford Health Systems Detroit Michigan United States 48202
15 University of Mississippi Medical Center Jackson Mississippi United States 39216
16 Washington University in St. Louis Saint Louis Missouri United States 63110
17 University of Nebraska Medical Center Omaha Nebraska United States 68198
18 NYU School of Medicine New York New York United States 10016
19 Cleveland Clinic Cleveland Ohio United States 44195
20 Ohio State University Columbus Ohio United States 43210
21 University of Pennsylvania Philadelphia Pennsylvania United States 19104
22 Medical University of South Carolina Charleston South Carolina United States 29425
23 University of Texas Southwestern Medical Center Dallas Texas United States 75390
24 Houston Methodist Hospital Houston Texas United States 77030
25 University of Utah Salt Lake City Utah United States 84132
26 Inova Heart and Vascular Institute Fairfax Virginia United States 22042
27 University of Washington Seattle Washington United States 98195

Sponsors and Collaborators

  • Ray Hershberger
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Human Genome Research Institute (NHGRI)

Investigators

  • Principal Investigator: Ray Hershberger, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Ray Hershberger, MD, Ohio State University
ClinicalTrials.gov Identifier:
NCT03037632
Other Study ID Numbers:
  • 2015H0309
  • R01HL128857
First Posted:
Jan 31, 2017
Last Update Posted:
Sep 9, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated

Study Results

No Results Posted as of Sep 9, 2021