Genetic Determinants of Sudden Cardiac Death

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Christine M. Albert, MD, MPH, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00064558
First received: July 8, 2003
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

To evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population.


Condition
Cardiovascular Diseases
Heart Diseases
Death, Sudden, Cardiac
Ventricular Arrhythmia
Arrhythmia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Genetic Determinants of Sudden Cardiac Death

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • sequence variation [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To determine if sequence variants in SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2 genes and other candidate genes are associated with an increased risk of SCD in broader populations.


Secondary Outcome Measures:
  • Single loci and SCD risk [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To test directly for associations between single loci that may have functional significance and SCD risk.


Enrollment: 2500
Study Start Date: July 2003
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Sudden cardiac death (SCD) affects 400,000 individuals each year in the U.S. alone. Over half have no evidence of heart disease prior to death, and the ability to identify those at risk and therefore prevent SCD is poor. Mutations in cardiac ion channel genes including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2 have been implicated in monogenic traits with a high risk of SCD, such as the long-QT, Brugada, sudden infant death syndrome, and catecholaminergic polymorphic ventricular tachycardia. Alterations in ion channel function can result in life-threatening ventricular arrhythmias in diverse disease states. Therefore, sequence variants in these genes that alter function or transcription of these ion channels may confer a predisposition to ventricular arrhythmia and SCD in broader populations.

DESIGN NARRATIVE:

This study will determine if sequence variants in the cardiac ion channel genes are associated with an increased risk of sudden cardiac death in apparently healthy populations. Cases of sudden cardiac death will be assembled from five NIH-funded prospective cohorts with a total of 106,314 individuals with existent blood samples. All cohorts are exceptionally well characterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints. The investigators will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts. Using these novel markers, they will define the haplotype block structure (SNPs in linkage disequilibrium) for the six cardiac ion channel genes, including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2. They will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes (haplotype tag SNPs) in both coding and non-coding regions and sudden cardiac death risk. They will also test directly for associations between single loci that may have functional significance and sudden cardiac death risk. An estimated 600 cases of well-documented sudden cardiac death will be confirmed over the first three years of the grant period, and these cases will be matched on age, sex, ethnicity, and geographic location to two control subjects from the same cohort. In addition, based upon known sex-differences in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, the investigators will specifically examine sex-differences in the risk of sudden cardiac death associated with sequence variation in these genes. In addition to these specific ion channel variants, other genetic hypotheses will be addressed in this case-control set. The findings generated will have substantial implications for our understanding of the sudden cardiac death syndrome and risk stratification in the general population.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Participants previously enrolled in the Physicians' Health Study I (protocol 1999-P-001468), Physicians' Health Study II (protocols 1999-P-003315, 1999-P-003318), Nurses' Health Study (protocols 1999-P-01114, 1999-P-010982), Women's Health Study (protocols 1999-P-001304, 1999-P-001478), Women's Antioxidant Cardiovascular Study (protocols 1999-P-001364, 1999-P-001611), and Health Professional Health Study approved through the Harvard School of Public Health IRB (protocols 0007PROC, 0103STOR)

Criteria

No eligibility criteria

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00064558

Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Christine M Albert, MD, MPH Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Christine M. Albert, MD, MPH, Director, Center for Arrhythmia Prevention, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00064558     History of Changes
Other Study ID Numbers: 1228, R01HL068070
Study First Received: July 8, 2003
Last Updated: January 22, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Cardiovascular Diseases
Death
Death, Sudden
Heart Diseases
Death, Sudden, Cardiac
Pathologic Processes
Heart Arrest

ClinicalTrials.gov processed this record on July 31, 2014