We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01873963
Recruitment Status : Active, not recruiting
First Posted : June 10, 2013
Last Update Posted : February 10, 2017
Information provided by (Responsible Party):

June 6, 2013
June 10, 2013
February 10, 2017
April 2013
February 2017   (Final data collection date for primary outcome measure)
Time to death [ Time Frame: 2 years ]
Same as current
Complete list of historical versions of study NCT01873963 on ClinicalTrials.gov Archive Site
  • Time to transplant [ Time Frame: 2 years ]
  • Time to normalized left ventricular size or function in dilated cardiomyopathy [ Time Frame: 2 years ]
  • Septal:Posterior wall thickness ratio in hypertrophic cardiomyopathy [ Time Frame: 2 years ]
  • Left ventricular outflow tract in hypertrophic cardiomyopathy [ Time Frame: 2 years ]
Same as current
Not Provided
Not Provided
Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)
Genotype-Phenotype Associations in Pediatric Cardiomyopathy
Cardiomyopathy in children is a serious disease which can result in death, disability, heart transplantation or serious heart rhythm disorders. Doctors know little about the causes of cardiomyopathy but would like to learn more. In fact, up to 50-75% of cases in children have no known cause. For this reason, the purpose of this study is to identify genes that cause cardiomyopathy or that influence how people with cardiomyopathy do over time. These findings could improve disease prevention, surveillance, early management, and prognosis.

Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. The long-term goal of this project is to identify the genetic basis of cardiomyopathy and to correlate these findings with clinical phenotypes for risk stratification. These findings could improve disease prevention, surveillance, early management, and prognosis.

The specific aims of this study are:

  1. To identify the disease-causing and disease-associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort.
  2. To identify genotype-phenotype correlations that allow for risk stratification and improve management and therapy.

Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of up to 700 pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. The biological parent(s) of enrolled participants will also be approached about participating and providing a blood sample for genetic testing. In addition to the parent(s), the participants siblings and other relatives may also be approached regarding enrollment, based on the pedigree and family history.

This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease-causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge and technical innovation to the translation of genomic data to clinical utility. These aims will provide critical genetic architecture data, identify variants with large effects, and enable genotype-phenotype correlations necessary for advancing management and therapy.

The Study will have two components: 1) clinical data collection by chart review and family interview, and 2) biospecimen collection and genetic testing.

Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Bio specimen blood samples were collected for patients enrolled in the PCM Genes study.
Non-Probability Sample
Pediatric cases of dilated, hypertrophic or restrictive cardiomyopathy and select relatives will be enrolled at 11 pediatric cardiology centers in the US and Canada.
  • Dilated Cardiomyopathy
  • Hypertrophic Cardiomyopathy
  • Restrictive Cardiomyopathy
Not Provided
Pediatric cardiomyopathy
Diagnosis of primary or idiopathic dilated, hypertrophic or restrictive cardiomyopathy. Diagnosis must have been made before the age of 18 and must be confirmed by established echocardiographic criteria or cardiac MRI (cMRI) at the time of diagnosis.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Active, not recruiting
March 2017
February 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient is alive. (except samples from deceased relatives who have consented for testing).Patients who are status-post heart transplant are eligible if pre-transplant longitudinal data are available.
  • Under age 18 years at the time of diagnosis of either primary or idiopathic dilated, hypertropic, or restrictive cardiomyopathy.
  • A diagnosis of cardiomyopathy which, at the time of diagnosis, was confirmed by echocardiographic criteria or cardiac MRI

Exclusion Criteria:

A patient is not eligible for enrollment if one or more of the following conditions are met at the time of presentation with cardiomyopathy:

  • Arrhythmogenic right ventricular dysplasia
  • Neuromuscular disease (defined by specific conditions)
  • Endocrine disease known to cause heart muscle disease (including infants of diabetic mothers)
  • History of rheumatic fever
  • Toxic exposures known to cause heart muscle disease (anthracyclines, mediastinal radiation, iron overload or heavy metal exposure)
  • HIV infection or born to an HIV positive mother
  • Kawasaki disease
  • Immunologic disease
  • Invasive cardiothoracic procedures or major surgery during the preceding month, except those specifically related to cardiomyopathy including left ventricular assist device (LVAD), extracorporeal membrane oxygenator (ECMO), and automatic implantable cardioverter/defibrillator (AICD) placement.
  • Uremia, active or chronic
  • Abnormal ventricular size or function that can be attributed to intense physical training or chronic anemia
  • Chronic arrhythmia, unless there are studies documenting inclusion criteria prior to the onset of arrhythmia (except a patient with chronic arrhythmia, subsequently ablated, whose cardiomyopathy persists after two months is not to be excluded).
  • Malignancy
  • Systemic Hypertension
  • Pulmonary parenchymal or vascular disease (e.g., cystic fibrosis, cor pulmonale, or pulmonary hypertension)
  • Ischemic coronary vascular disease
  • Association with drugs known to cause hypertrophy (e.g., growth hormone, corticosteroids, cocaine)
  • Genetic syndrome or chromosomal abnormality known to be associated with cardiomyopathy
Sexes Eligible for Study: All
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
1R01HL111459-01( U.S. NIH Grant/Contract )
1R01HL111459-01 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Steve Lipshultz, Wayne State University
Wayne State University
  • New England Research Institutes
  • Children's Hospital Medical Center, Cincinnati
  • Washington University School of Medicine
  • Children's Hospital of Philadelphia
  • Columbia University
  • Boston Children’s Hospital
  • Ann & Robert H Lurie Children's Hospital of Chicago
  • Primary Children's Hospital
  • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Stollery Children's Hospital
  • National Heart, Lung, and Blood Institute (NHLBI)
  • University of Miami
  • Children's Hospital Colorado
  • Indiana University
Principal Investigator: Steven E Lipshultz, MD Wayne State University
Wayne State University
February 2017