Dilated CardiomyopathyNCT01873963
Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)
An observational study of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy, run by Wayne State University at 12 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Restrictive Cardiomyopathy
- How many people
- 544 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Apr 2013to 31 Mar 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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)
Show all 19Show fewer
- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital Boston
Boston, Massachusetts, 02115
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Miami, Jackson Memorial Hospital
Miami, Florida, 33136
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Children's Hospital of New York, Columbia Presbyterian Medical Center
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Primary Children's Medical Center
Salt Lake City, Utah, 84113
Washington University School of Medicine
St Louis, Missouri, 63110
Children's Hospital at Montefiore
The Bronx, New York, 10467
About this study
Official title: 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.
Read the 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:
- To identify the disease-causing and disease-associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort.
- 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.
- Medical subject headings
- Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Cardiomyopathy, Restrictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to death
Measured: 2 years
Secondary outcomes (4)
Time to transplant
Measured: 2 years
Time to normalized left ventricular size or function in dilated cardiomyopathy
Measured: 2 years
Septal:Posterior wall thickness ratio in hypertrophic cardiomyopathy
Measured: 2 years
Left ventricular outflow tract in hypertrophic cardiomyopathy
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2013 (estimated)
- Study startApr 2013
- Primary completionFeb 2017
- Study completion31 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dilated CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 544 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- Carelon Research, 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
- Responsible party
- Principal investigator, Steve Lipshultz, Wayne State University
- Investigators
- Steven E Lipshultz, MD, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01873963
- Sponsor's protocol ID
- 1R01HL111459-01
- Other IDs
- 1R01HL111459-01
- Status last verified
- Apr 2018
- First submitted
- 6 Jun 2013
- Last updated
- 1 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pahl E, Ware SM, Shi L, Colan SD, Everitt MD, Sleeper LA, Sridhar A, Schubert JA, Canter CE, Hsu DT, Webber SA, Kantor PF, Rossano JW, Chung WK, Lee TM, Towbin JA, Lal AK, Tariq M, Bhatnagar S, Dexheimer PJ, Aronow BJ, Martin LJ, Miller EM, Bansal N, Lipshultz SE. Genotype-Phenotype Associations in Pediatric Hypertrophic Cardiomyopathy: A Study From the Pediatric Cardiomyopathy Registry. JACC Heart Fail. 2026 Sep 17:103355. doi: 10.1016/j.jchf.2026.103355. Online ahead of print.
PubMed 42758059Ware SM, Wilkinson JD, Tariq M, Schubert JA, Sridhar A, Colan SD, Shi L, Canter CE, Hsu DT, Webber SA, Dodd DA, Everitt MD, Kantor PF, Addonizio LJ, Jefferies JL, Rossano JW, Pahl E, Rusconi P, Chung WK, Lee T, Towbin JA, Lal AK, Bhatnagar S, Aronow B, Dexheimer PJ, Martin LJ, Miller EM, Sleeper LA, Razoky H, Czachor J, Lipshultz SE; Pediatric Cardiomyopathy Registry Study Group. Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study. J Am Heart Assoc. 2021 May 4;10(9):e017731. doi: 10.1161/JAHA.120.017731. Epub 2021 Apr 28.
PubMed 33906374
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype-Phenotype Associations in Pediatric Cardiomyopathy
- ClinicalTrials.gov ID
- NCT01873963
- Acronym / sponsor ID
- 1R01HL111459-01
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 544 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- Carelon Research, 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
- Study start
- Apr 2013
- Primary completion
- Feb 2017 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 10 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- To identify the disease-causing and disease-associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort.
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Time to death
Time frame: 2 years
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2018.
- Derived from this study: PubMed 42758059Pahl E, Ware SM, Shi L, Colan SD, Everitt MD, Sleeper LA, Sridhar A, Schubert JA, Canter CE, Hsu DT, Webber SA, Kantor PF, Rossano JW, Chung WK, Lee TM, Towbin JA, Lal AK, Tariq M, Bhatnagar S, Dexheimer PJ, Aronow BJ, Martin LJ, Miller EM, Bansal N, Lipshultz SE. Genotype-Phenotype Associations in Pediatric Hypertrophic Cardiomyopathy: A Study From the Pediatric Cardiomyopathy Registry. JACC Heart Fail. 2026 Sep 17:103355. doi: 10.1016/j.jchf.2026.103355. Online ahead of print.
- Derived from this study: PubMed 33906374Ware SM, Wilkinson JD, Tariq M, Schubert JA, Sridhar A, Colan SD, Shi L, Canter CE, Hsu DT, Webber SA, Dodd DA, Everitt MD, Kantor PF, Addonizio LJ, Jefferies JL, Rossano JW, Pahl E, Rusconi P, Chung WK, Lee T, Towbin JA, Lal AK, Bhatnagar S, Aronow B, Dexheimer PJ, Martin LJ, Miller EM, Sleeper LA, Razoky H, Czachor J, Lipshultz SE; Pediatric Cardiomyopathy Registry Study Group. Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study. J Am Heart Assoc. 2021 May 4;10(9):e017731. doi: 10.1161/JAHA.120.017731. Epub 2021 Apr 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven E Lipshultz, MD principal investigator
Wayne State University
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy, run by Wayne State University at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to death (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01873963, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2018.