DCM Precision Medicine Study

March 18, 2024 updated by: Ray Hershberger

Precision Medicine for Dilated Cardiomyopathy in European and African Ancestry

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Enrollment (Estimated)

6500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona Sarver Heart Center
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Palo Alto, California, United States, 94304
        • Stanford University
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Medstar Washington Hospital Center (DC)
    • Florida
      • Miami, Florida, United States, 33143
        • South Miami Heart Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Sciences Center in New Orleans
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48187
        • University of Michigan
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New York
      • New York, New York, United States, 10016
        • NYU School of Medicine
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22042
        • Inova Heart and Vascular Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Communication Tool
Behavioral: Family Heart Talk Booklet
No Intervention: No Communication Tool

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Family clinical screening completed within 12 months from proband enrollment.
Time Frame: 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
12 months from proband enrollment.
Living first-degree relative adheres to cardiovascular surveillance recommendations after return of genetic results.
Time Frame: 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.
2.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ray Hershberger

Collaborators

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2016

Primary Completion (Estimated)

April 30, 2024

Study Completion (Estimated)

April 30, 2024

Study Registration Dates

First Submitted

January 27, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimated)

January 31, 2017

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015H0309
  • R01HL128857 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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