Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers)

Hypertrophic Cardiomyopathy Clinical Trial

Official title:

Cardiac Biomarkers in Pediatric Cardiomyopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01873976
• Other study ID #: 1R01HL109090-01A1
• Status: Active, not recruiting
• Start date: June 2013
• Est. completion date: June 2022

Study information

• Verified date: October 2020
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Cardiomyopathy is a disease of the heart muscle. It is rare, but it can be serious. Cardiomyopathy in children can result in death, disability, heart transplantation or serious heart rhythm disorders. Natural substances in the blood called cardiac biomarkers can be measured in the laboratory and could be a less invasive way (compared to echocardiograms or MRIs) to detect heart dysfunction in children with cardiomyopathy. Little is known about how useful and valid cardiac biomarkers are in the diagnosis and determination of the symptoms in children with cardiomyopathy. The long-term goal of this project is to study how helpful measuring cardiac biomarkers in children with cardiomyopathy is to their doctors in managing the care of these patients as well as improving their overall health. Measures of these cardiac biomarkers could help doctors in determining how best to care for a child with cardiomyopathy, including when to consider heart transplantation as a treatment option.

Description:

Pediatric cardiomyopathy is a heterogeneous disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. Highly sensitive and specific cardiac biomarkers or panels of biomarkers, representing different pathologic mechanisms or pathways, are the least invasive (a particularly important consideration in children) and most-cost-effective approach to the early detection of cardiac dysfunction. The long-term goal of this project is to identify such biomarkers in children with cardiomyopathy. These findings could represent a major advance in determining the most appropriate evidence-based clinical care for these children, including when to consider heart transplantation.

The specific aims of this study are:

1. To determine the ability of established and novel cardiac biomarkers to predict short- and long-term outcomes in children with newly diagnosed (incident) dilated cardiomyopathy (DCM)

2. To assess the clinical utility of cardiac biomarkers of collagen metabolism in determining the presence of myocardial fibrosis, as established by cardiac MRI (cMRI), and left ventricular (LV) diastolic dysfunction, as established by echocardiography in both newly diagnosed and existing cases of idiopathic and familial hypertrophic cardiomyopathy (HCM) in children.

3. To determine whether longitudinal changes in cardiac biomarkers are associated with worsening heart failure (HF) class in clinically stable children with dilated or hypertrophic cardiomyopathy. This study will determine the importance of serological biomarkers, in conjunction with cardiac imaging, in the early identification of heart disease before cardiac remodeling and functional impairment have become irreversible in a pediatric population.

This is a 5-year prospective study of up to 480 children with either primary dilated or hypertrophic cardiomyopathy. The study will have three components: 1) clinical data collection by chart review, 2) biospecimen collection and testing, and 3) centralized review and measurement of echocardiograms and cMRIs.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 288
• Est. completion date: June 2022
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 20 Years

Eligibility

Inclusion Criteria:

• Patient is alive and has not received a transplant prior to enrollment in the study.

• Under age 21 years at age of enrollment

• For Group 1 (incident DCM), a case of DCM presenting to a study site within 2 years of the original cardiomyopathy diagnosis

• Group 2 (incident/recent HCM), a new or existing diagnosis of idiopathic or familial HCM with a cMRI within 12 months of diagnosis

• Group 3 (prevalent HCM or DCM), any child with a diagnosis of DCM or idiopathic, familial, or HCM due to a known disease-causing mutation who has survived transplant-free at least 12 months from the date of original cardiomyopathy diagnosis

• For all 3 groups, diagnosis of cardiomyopathy must be confirmed by Echocardiographic or cMRI criteria

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:

• Any cardiomyopathy diagnosis other than DCM or idiopathic HCM, familial HCM or HCM due to a known disease-causing gene

• 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

• Congenital heart defects unassociated with malformation syndromes (e.g., valvular heart disease or congenital coronary artery malformations)

• 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 (e.g., growth hormone, corticosteroids, cocaine) or other diseases known to cause hypertrophy

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Cardiomyopathy, Hypertrophic
• Dilated Cardiomyopathy
• Hypertrophic Cardiomyopathy

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital, University of Alberta	Edmonton	Alberta
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Ann and Robert H. Lurie Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Children's Hospital of New York, Columbia Presbyterian Medical Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UMPC	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah

Sponsors (15)

Lead Sponsor

Collaborator

Wayne State University

Ann & Robert H Lurie Children's Hospital of Chicago, Boston Children's Hospital, Children's Hospital Colorado, Children's Hospital Medical Center, Cincinnati, Children's Hospital of Philadelphia, Columbia University, HealthCore-NERI, Le Bonheur Children's Hospital, Monroe Carell Jr. Children's Hospital at Vanderbilt, Montefiore Medical Center, Primary Children's Hospital, Stollery Children's Hospital, University of Pittsburgh, Washington University School of Medicine

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Death		2 years
Secondary	Time to heart transplant		2 years
Secondary	Worsening heart failure		2 years