Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)
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ClinicalTrials.gov Identifier: NCT00682695 |
Recruitment Status :
Active, not recruiting
First Posted : May 22, 2008
Last Update Posted : December 7, 2023
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Tracking Information | |||||
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First Submitted Date | May 20, 2008 | ||||
First Posted Date | May 22, 2008 | ||||
Last Update Posted Date | December 7, 2023 | ||||
Study Start Date | September 1997 | ||||
Estimated Primary Completion Date | October 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
Perform deep DNA sequencing of Chr 1q22 [ Time Frame: Ongoing to be completed at the end of June 2021 ] Perform deep DNA sequencing of Chr 1q22 among non-Hispanic white and black ICH cases and controls to identify all genomic variation within these regions.
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Original Primary Outcome Measures |
The analysis of the presence of specific genetic markers such as APOE4, APOE2 and Alpha-1-Antitrypsin gene mutations in people with hemorrhagic stroke versus the control group. [ Time Frame: Ongoing to be completed at the end of June 2008 ] | ||||
Change History | |||||
Current Secondary Outcome Measures |
Collect and analyze DNA, RNA, and serum on ICH cases and matched control participants. [ Time Frame: Ongoing to be completed at the end of June 2021 ] Collect and analyze DNA, RNA, and serum on ICH cases and matched controls both at the time of ICH and in the convalescent period. We will perform RNA expression profiling between cases and controls and over time in cases.
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Original Secondary Outcome Measures |
Analysis of risk factors such as age, race, gender, current smoking, heavy alcohol use, use of anti-coagulants, diabetes, hemorrhagic stroke family history, hypertension, etc. in people with hemorrhagic stroke versus the control group. [ Time Frame: Ongoing to be completed at the end of June 2008 ] | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | Genetic and Environmental Risk Factors for Hemorrhagic Stroke | ||||
Official Title | Genetic and Environmental Risk Factors for Hemorrhagic Stroke | ||||
Brief Summary | The purpose of this study is to find risk factors for hemorrhagic stroke. | ||||
Detailed Description | The proposed research builds on the most robust, statistically significant and replicated association identified to determine the mechanism by which it may relate to intracerebral hemorrhage (ICH) risk. Given that ICH is an extreme phenotype on a spectrum of manifestations of cerebral small vessel disease, the findings that emerge from our proposed studies offer the promise of broad impact for research and treatment in a wide variety of cerebrovascular disorders. In the genetic epidemiology of hemorrhagic stroke, we propose to perform an in-depth fine-mapping of the entire 1q22 genomic region (~250kb) to investigate whether genetic variants influence gene expression that correlates with ICH status or changes in expression over time in ICH cases. As existing samples were not processed for gene expression analysis, we will recruit 500 non-lobar ICH cases (~150 black, ~350 white) and 1000 controls (300 black, 700 white) to correlate sequence variation with gene expression levels in the same samples. Identified associations will be replicated in 6,000 cases of ICH and 9,361 individuals in the CHARGE consortium with MRI white matter hyperintensity volume measurements and 5,000 controls. The current proposal takes the next logical step by pursuing the most promising findings of our Genome-Wide Association Study (GWAS) to complete the following aims: Specific Aim #1: Perform deep DNA sequencing of Chr 1q22 among non-Hispanic white and black ICH cases and controls to identify all genomic variation within these regions and test the following: Hypothesis #1a: Variants strongly associated with ICH risk at 1q22 are either directly causal or in linkage disequilibrium to causal variants that influence ICH risk, and sequencing of these regions will reveal both common and rare variants that exert this causal influence. Hypothesis #1b: Variants strongly associated with ICH risk at 1q22 will be associated with risk of, or severity of, leukoaraiosis. Specific Aim #2: Prospectively collect DNA, RNA, and serum on ICH cases and geographic region site-specific controls both at the time of ICH and in the convalescent period. We will perform RNA expression profiling between cases and controls and over time in cases. We will compute expression quantitative trait locus (eQTL) analysis with Single Nucleotide Polymorphisms (SNPs) arising from Aim 1. We will also determine whether alternatively spliced transcripts differ between cases and controls. Hypothesis #2a: Variation in gene expression or alternatively spliced transcripts affects risk of ICH. Hypothesis #2b: Variations identified by DNA sequencing will affect gene expression and/or alternatively spliced transcripts that affect risk of ICH. |
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Study Type | Observational | ||||
Study Design | Observational Model: Ecologic or Community Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Retention: Samples With DNA Description: whole blood DNA, RNA and Complete Blood Count (CBC)
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Sampling Method | Non-Probability Sample | ||||
Study Population | This study will be limited to physician-reviewed cases of people who have had a hemorrhagic stroke. | ||||
Condition | Stroke | ||||
Intervention | Not Provided | ||||
Study Groups/Cohorts | 1
Participants who have had a hemorrhagic stroke at University of Maryland, University of Cincinnati, Massachusetts General Hospital, Duke University, Columbia University and University of Chicago Illinois, age 18 years or greater. Ability of the patient or legal representative to provide informed consent. Racial/ethnic category meets one of the following: African American, Caucasian or Hispanic. Healthy volunteers who are matched to the study cases with hemorrhagic stroke within +/- 5 years of age, same gender and same race. |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Active, not recruiting | ||||
Estimated Enrollment |
1000 | ||||
Original Actual Enrollment |
3187 | ||||
Estimated Study Completion Date | October 2024 | ||||
Estimated Primary Completion Date | October 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | Yes | ||||
Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT00682695 | ||||
Other Study ID Numbers | NS36695 2U01NS036695-15A1 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Current Responsible Party | Daniel Woo, University of Cincinnati | ||||
Original Responsible Party | Joseph P. Broderick, MD, Chairman of the Department of Neurology, University of Cincinnati College of Medicine | ||||
Current Study Sponsor | University of Cincinnati | ||||
Original Study Sponsor | Same as current | ||||
Collaborators |
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Investigators |
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PRS Account | University of Cincinnati | ||||
Verification Date | December 2023 |