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Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)

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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):

Study Description
Brief Summary:
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.

Condition or disease
Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Restrictive Cardiomyopathy

Detailed Description:

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.

Study Design

Study Type : Observational
Actual Enrollment : 544 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genotype-Phenotype Associations in Pediatric Cardiomyopathy
Study Start Date : April 2013
Primary Completion Date : February 2017
Estimated Study Completion Date : March 2017

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :
  1. Time to death [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Time to transplant [ Time Frame: 2 years ]
  2. Time to normalized left ventricular size or function in dilated cardiomyopathy [ Time Frame: 2 years ]
  3. Septal:Posterior wall thickness ratio in hypertrophic cardiomyopathy [ Time Frame: 2 years ]
  4. Left ventricular outflow tract in hypertrophic cardiomyopathy [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA
Bio specimen blood samples were collected for patients enrolled in the PCM Genes study.

Eligibility Criteria

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pediatric cases of dilated, hypertrophic or restrictive cardiomyopathy and select relatives will be enrolled at 11 pediatric cardiology centers in the US and Canada.

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01873963

United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
University of Miami, Jackson Memorial Hospital
Miami, Florida, United States, 33136
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Children's Hospital at Montefiore
Bronx, New York, United States, 10467
Children's Hospital of New York, Columbia Presbyterian Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
Canada, Alberta
Stollery Children's Hospital
Edmonton, Alberta, Canada, T6G 2B7
Sponsors and Collaborators
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
More Information

Responsible Party: Steve Lipshultz, Schotanus Family Endowed Chair of Pediatrics, Professor and Chair, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine; President, University Pediatricians and Pediatrician-in-Chief, Children's Hospital of Michigan, Wayne State University
ClinicalTrials.gov Identifier: NCT01873963     History of Changes
Other Study ID Numbers: 1R01HL111459-01 ( U.S. NIH Grant/Contract )
First Posted: June 10, 2013    Key Record Dates
Last Update Posted: February 10, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
Cardiomyopathy, Restrictive
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases