Trial record 2 of 2 for:    "familial restrictive cardiomyopathy" OR "Cardiomyopathy, Restrictive"

Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Miami
Sponsor:
Collaborators:
New England Research Institutes
Children's Hospital Medical Center, Cincinnati
Washington University School of Medicine
Children's Hospital of Philadelphia
Columbia University
Children's Hospital Boston
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
Information provided by (Responsible Party):
Steven E. Lipshultz, MD, University of Miami
ClinicalTrials.gov Identifier:
NCT01873963
First received: June 6, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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
Dilated Cardiomyopathy
Hypertrophic Cardiomyopathy
Restrictive Cardiomyopathy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genotype-Phenotype Associations in Pediatric Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Time to death [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to transplant [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to normalized left ventricular size or function in dilated cardiomyopathy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Septal:Posterior wall thickness ratio in hypertrophic cardiomyopathy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Left ventricular outflow tract in hypertrophic cardiomyopathy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 700
Study Start Date: April 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/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.

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.

  Eligibility

Genders Eligible for Study:   Both
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.

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01873963

Contacts
Contact: Steven E Lipshultz, MD 305-243-3993 SLipshultz@med.miami.edu
Contact: Jay Wilkinson, MD MPH jwilkins@med.miami.edu

Locations
United States, Florida
University of Miami, Jackson Memorial Hospital Recruiting
Miami, Florida, United States, 33136
Contact: Paolo Rusconi, MD       prusconi@med.miami.edu   
Principal Investigator: Paolo Rusconi, MD         
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Elfriede Pahl, MD       EPahl@luriechildrens.org   
Principal Investigator: Elfriede Pahl, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Steven Colan, MD       Steven.Colan@cardio.chboston.org   
Principal Investigator: Steven Colan, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Charles Canter, MD       canter@kids.wustl.edu   
Principal Investigator: Charles Canter, MD         
United States, New York
Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Daphne Hsu, MD       dhsu@montefiore.org   
Principal Investigator: Daphne Hsu, MD         
Children's Hospital of New York, Columbia Presbyterian Medical Center Recruiting
New York, New York, United States, 10032
Contact: Linda Addonizio, MD       lja1@mail.cumc.columbia.edu   
Principal Investigator: Linda Addonizio, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Stephanie Ware, MD, PhD       Stephanie.Ware@cchmc.org   
Principal Investigator: Stephanie Ware, MD, PhD         
Principal Investigator: Jeffrey Towbin, MD         
Sub-Investigator: John L Jeffries, MD, MPH         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Rossano, MD MS       RosanoJ@email.chop.edu   
Principal Investigator: Joseph Rossano, MD MS         
United States, Tennessee
Monroe Carell Jr. Children's Hospital at Vanderbilt Recruiting
Nashville, Tennessee, United States, 37232
Contact: Steven Webber, MBChB, MRCP       steven.a.webber@vanderbilt.edu   
Principal Investigator: Steven Webber, MBChB, MRCP         
Sub-Investigator: Debra Dodd, MD         
United States, Utah
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Melanie Everitt, MD       Melanie.Everitt@imail.org   
Principal Investigator: Melanie Everitt, MD         
Canada, Alberta
Stollery Children's Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Paul Kantor, MBBCh, FRCPC       paul.kantor@albertahealthservices.ca   
Principal Investigator: Paul Kantor, MBBCh, FRCPC         
Sponsors and Collaborators
University of Miami
New England Research Institutes
Children's Hospital Medical Center, Cincinnati
Washington University School of Medicine
Children's Hospital of Philadelphia
Columbia University
Children's Hospital Boston
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
Investigators
Principal Investigator: Steven E Lipshultz, MD University of Miami
  More Information

No publications provided

Responsible Party: Steven E. Lipshultz, MD, George Batchelor Professor of Pediatrics, Professor of Epidemiology and Public Health, Professor of Medicine (Oncology); Director, Batchelor Children's Research Institute, University of Miami
ClinicalTrials.gov Identifier: NCT01873963     History of Changes
Other Study ID Numbers: 1R01HL111459-01
Study First Received: June 6, 2013
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board

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

ClinicalTrials.gov processed this record on July 29, 2014