Cardiovascular DiseasesNCT00064558
Genetic Determinants of Sudden Cardiac Death
An observational study of Cardiovascular Diseases and Heart Diseases, run by Brigham and Women's Hospital.
Trial summary
To evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Death, Sudden, Cardiac
- How many people
- 2,500 participants
- Where
- No sites listed yet
- Study dates
- Jul 2003to Jun 2008
- 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
No eligibility criteria.
About this study
To evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population.
Read the 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 our ability to identify those at risk and, therefore prevent SCD, is poor. Mutations in cardiac ion channel genes including SCN5A, KCNQ1, KCNH2, KCNE1, KCNE2 and RyR2 have been implicated in monogenic traits with high risk of SCD, such as the long-QT, Brugada, sudden infant death syndrome (SIDS), 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 research program proposes to determine if sequence variants in the above and other candidate genes are associated with an increased risk of SCD in apparently-healthy populations. Cases of SCD will be assembled from 5 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. We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts for the 6 genes. We 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 of candidate genes and SCD risk. We will also test directly for associations between single loci that may have functional significance and SCD risk. An estimated 600 cases of well-documented SCD will be confirmed over the first 3 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 difference in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, we will specifically examine sex difference in the risk of SCD associated with sequence variation in these genes. The findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population.
- Conditions
- Cardiovascular Diseases, Heart Diseases, Death, Sudden, Cardiac, Ventricular Arrhythmia, Arrhythmia
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Death, Sudden, Cardiac, Arrhythmias, Cardiac
What is being measured
The primary outcome is the main question the study is designed to answer.
sequence variation
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.
Measured: Ongoing
Secondary outcomes (1)
Single loci and SCD risk
To test directly for associations between single loci that may have functional significance and SCD risk.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2003 (estimated)
- Study startJul 2003
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 2,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Christine M. Albert, MD, MPH, Brigham and Women's Hospital
- Investigators
- Christine M Albert, M.D., M.P.H., Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00064558
- Sponsor's protocol ID
- 1228
- Other IDs
- R01HL068070
- Status last verified
- Oct 2025
- First submitted
- 8 Jul 2003
- Last updated
- 7 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Determinants of Sudden Cardiac Death
- ClinicalTrials.gov ID
- NCT00064558
- Acronym / sponsor ID
- 1228
- Conditions
- Cardiovascular Diseases, Heart Diseases, Death, Sudden, Cardiac, Ventricular Arrhythmia, Arrhythmia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,500 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 2003
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 10 Jul 2003 (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.
To evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population.
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 our ability to identify those at risk and, therefore prevent SCD, is poor. Mutations in cardiac ion channel genes including SCN5A, KCNQ1, KCNH2, KCNE1, KCNE2 and RyR2 have been implicated in monogenic traits with high risk of SCD, such as the long-QT, Brugada, sudden infant death syndrome (SIDS), 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 research program proposes to determine if sequence variants in the above and other candidate genes are associated with an increased risk of SCD in apparently-healthy populations. Cases of SCD will be assembled from 5 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. We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts for the 6 genes. We 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 of candidate genes and SCD risk. We will also test directly for associations between single loci that may have functional significance and SCD risk. An estimated 600 cases of well-documented SCD will be confirmed over the first 3 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 difference in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, we will specifically examine sex difference in the risk of SCD associated with sequence variation in these genes. The findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
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
sequence variation
Time frame: Ongoing
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.
1 secondary outcome
Single loci and SCD risk
Time frame: Ongoing
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 7 Oct 2025.
- Individual participant dataSharing planned: No
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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.
Christine M Albert, M.D., M.P.H. principal investigator
Brigham and Women's Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by Brigham and Women's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 7 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
sequence variation (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Oct 2025.