Genetic and Environmental Risk Factors for Hemorrhagic Stroke

NCT ID: NCT00682695

Last Updated: 2025-07-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-01-01

Study Completion Date

2029-12-31

Brief Summary

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The purpose of this study is to find risk factors for hemorrhagic stroke.

Detailed Description

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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.

Conditions

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Stroke

Study Design

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Observational Model Type

ECOLOGIC_OR_COMMUNITY

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Age 18 or older
* Resident (6 months or longer) within the recruitment center
* Fulfillment of the criteria for spontaneous ICH
* No evidence of trauma, brain tumor/metastases or infectious processes as a cause of the hemorrhage
* Ability of the patient or legal representative to provide consent for an interview, blood pressure determinations and DNA sampling

Exclusion Criteria

* N/A
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Duke University, Durham, NC

UNKNOWN

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

University of Illinois at Chicago

OTHER

Sponsor Role collaborator

Baptist Health, Louisville

OTHER

Sponsor Role collaborator

State University of New York at Buffalo

OTHER

Sponsor Role lead

Responsible Party

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Daniel Woo

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daniel Woo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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University of Illinois Chicago

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

Baptist Health Louisville

Louisville, Kentucky, United States

Site Status RECRUITING

University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status NOT_YET_RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lee A Gilkerson, RN, BSN

Role: CONTACT

513-558-6140

Facility Contacts

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Maureen Hillman

Role: primary

312-355-3863

Karin Cryan

Role: primary

502-259-5564

Tiffany Watson

Role: primary

410-706-1902

Christina Kourkoulis

Role: primary

617-726-5358

Angela Velazquez

Role: primary

212-305-6071

Andreea Podgoreanu

Role: primary

919-681-4054

Lee A Gilkerson, RN, BSN

Role: primary

513-558-6140

References

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Woo D, Sauerbeck LR, Kissela BM, Khoury JC, Szaflarski JP, Gebel J, Shukla R, Pancioli AM, Jauch EC, Menon AG, Deka R, Carrozzella JA, Moomaw CJ, Fontaine RN, Broderick JP. Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke. 2002 May;33(5):1190-5. doi: 10.1161/01.str.0000014774.88027.22.

Reference Type BACKGROUND
PMID: 11988589 (View on PubMed)

Kissela BM, Sauerbeck L, Woo D, Khoury J, Carrozzella J, Pancioli A, Jauch E, Moomaw CJ, Shukla R, Gebel J, Fontaine R, Broderick J. Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke. 2002 May;33(5):1321-6. doi: 10.1161/01.str.0000014773.57733.3e.

Reference Type BACKGROUND
PMID: 11988610 (View on PubMed)

Woo D, Kissela BM, Khoury JC, Sauerbeck LR, Haverbusch MA, Szaflarski JP, Gebel JM, Pancioli AM, Jauch EC, Schneider A, Kleindorfer D, Broderick JP. Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study. Stroke. 2004 Jun;35(6):1360-4. doi: 10.1161/01.STR.0000127786.16612.A4. Epub 2004 Apr 15.

Reference Type BACKGROUND
PMID: 15087556 (View on PubMed)

Woo D, Haverbusch M, Sekar P, Kissela B, Khoury J, Schneider A, Kleindorfer D, Szaflarski J, Pancioli A, Jauch E, Moomaw C, Sauerbeck L, Gebel J, Broderick J. Effect of untreated hypertension on hemorrhagic stroke. Stroke. 2004 Jul;35(7):1703-8. doi: 10.1161/01.STR.0000130855.70683.c8. Epub 2004 May 20.

Reference Type BACKGROUND
PMID: 15155969 (View on PubMed)

Flaherty ML, Woo D, Haverbusch M, Sekar P, Khoury J, Sauerbeck L, Moomaw CJ, Schneider A, Kissela B, Kleindorfer D, Broderick JP. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005 May;36(5):934-7. doi: 10.1161/01.STR.0000160756.72109.95. Epub 2005 Mar 24.

Reference Type BACKGROUND
PMID: 15790947 (View on PubMed)

Sauerbeck LR, Khoury JC, Woo D, Kissela BM, Moomaw CJ, Broderick JP. Smoking cessation after stroke: education and its effect on behavior. J Neurosci Nurs. 2005 Dec;37(6):316-9, 325.

Reference Type BACKGROUND
PMID: 16396084 (View on PubMed)

Woo D, Kaushal R, Chakraborty R, Woo J, Haverbusch M, Sekar P, Kissela B, Pancioli A, Jauch E, Kleindorfer D, Flaherty M, Schneider A, Khatri P, Sauerbeck L, Khoury J, Deka R, Broderick J. Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage. Stroke. 2005 Sep;36(9):1874-9. doi: 10.1161/01.STR.0000177891.15082.b9. Epub 2005 Aug 11.

Reference Type BACKGROUND
PMID: 16100021 (View on PubMed)

Woo D, Sekar P, Chakraborty R, Haverbusch MA, Flaherty ML, Kissela BM, Kleindorfer D, Schneider A, Khoury J, Sauerbeck LR, Deka R, Broderick JP. Genetic epidemiology of intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2005 Nov-Dec;14(6):239-43. doi: 10.1016/j.jstrokecerebrovasdis.2005.08.002.

Reference Type BACKGROUND
PMID: 16557295 (View on PubMed)

Flaherty ML, Haverbusch M, Kissela B, Kleindorfer D, Schneider A, Sekar P, Moomaw CJ, Sauerbeck L, Broderick JP, Woo D. Perimesencephalic subarachnoid hemorrhage: incidence, risk factors, and outcome. J Stroke Cerebrovasc Dis. 2005 Nov-Dec;14(6):267-71. doi: 10.1016/j.jstrokecerebrovasdis.2005.07.004.

Reference Type BACKGROUND
PMID: 16518463 (View on PubMed)

Flaherty ML, Woo D, Haverbusch M, Moomaw CJ, Sekar P, Sauerbeck L, Kissela B, Kleindorfer D, Broderick JP. Potential applicability of recombinant factor VIIa for intracerebral hemorrhage. Stroke. 2005 Dec;36(12):2660-4. doi: 10.1161/01.STR.0000189634.08400.82. Epub 2005 Nov 3.

Reference Type BACKGROUND
PMID: 16269646 (View on PubMed)

Woo D, Kaushal R, Kissela B, Sekar P, Wolujewicz M, Pal P, Alwell K, Haverbusch M, Ewing I, Miller R, Kleindorfer D, Flaherty M, Chakraborty R, Deka R, Broderick J. Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study. Stroke. 2006 Feb;37(2):371-6. doi: 10.1161/01.STR.0000198843.72824.0a. Epub 2005 Dec 22.

Reference Type BACKGROUND
PMID: 16373644 (View on PubMed)

Flaherty ML, Haverbusch M, Sekar P, Kissela B, Kleindorfer D, Moomaw CJ, Sauerbeck L, Schneider A, Broderick JP, Woo D. Long-term mortality after intracerebral hemorrhage. Neurology. 2006 Apr 25;66(8):1182-6. doi: 10.1212/01.wnl.0000208400.08722.7c.

Reference Type BACKGROUND
PMID: 16636234 (View on PubMed)

Flaherty ML, Haverbusch M, Sekar P, Kissela BM, Kleindorfer D, Moomaw CJ, Broderick JP, Woo D. Location and outcome of anticoagulant-associated intracerebral hemorrhage. Neurocrit Care. 2006;5(3):197-201. doi: 10.1385/NCC:5:3:197.

Reference Type BACKGROUND
PMID: 17290088 (View on PubMed)

Kaushal R, Pal P, Alwell K, Haverbusch M, Flaherty M, Moomaw C, Sekar P, Kissela B, Kleindorfer D, Chakraborty R, Broderick J, Deka R, Woo D. Association of ALOX5AP with ischemic stroke: a population-based case-control study. Hum Genet. 2007 Jun;121(5):601-7. doi: 10.1007/s00439-007-0338-y. Epub 2007 Mar 27.

Reference Type BACKGROUND
PMID: 17387518 (View on PubMed)

Eden SV, Morgenstern LB, Sekar P, Moomaw CJ, Haverbusch M, Flaherty ML, Broderick JP, Woo D. The role of race in time to treatment after subarachnoid hemorrhage. Neurosurgery. 2007 May;60(5):837-43; discussion 837-43. doi: 10.1227/01.NEU.0000255451.82483.50.

Reference Type BACKGROUND
PMID: 17460518 (View on PubMed)

Kaushal R, Woo D, Pal P, Haverbusch M, Xi H, Moomaw C, Sekar P, Kissela B, Kleindorfer D, Flaherty M, Sauerbeck L, Chakraborty R, Broderick J, Deka R. Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes. BMC Med Genet. 2007 Jul 31;8:49. doi: 10.1186/1471-2350-8-49.

Reference Type BACKGROUND
PMID: 17672902 (View on PubMed)

Flaherty ML, Kissela B, Woo D, Kleindorfer D, Alwell K, Sekar P, Moomaw CJ, Haverbusch M, Broderick JP. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology. 2007 Jan 9;68(2):116-21. doi: 10.1212/01.wnl.0000250340.05202.8b.

Reference Type BACKGROUND
PMID: 17210891 (View on PubMed)

Kharofa J, Sekar P, Haverbusch M, Moomaw C, Flaherty M, Kissela B, Broderick J, Woo D. Selective serotonin reuptake inhibitors and risk of hemorrhagic stroke. Stroke. 2007 Nov;38(11):3049-51. doi: 10.1161/STROKEAHA.107.491472. Epub 2007 Sep 27.

Reference Type BACKGROUND
PMID: 17901378 (View on PubMed)

Other Identifiers

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2U01NS036695-15A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NS36695

Identifier Type: -

Identifier Source: org_study_id

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