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Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00682695
Recruitment Status : Recruiting
First Posted : May 22, 2008
Last Update Posted : February 23, 2022
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Maryland, Baltimore
Massachusetts General Hospital
Duke University, Durham, NC
Columbia University
University of Illinois at Chicago
Baptist Health, Louisville
Information provided by (Responsible Party):
Daniel Woo, University of Cincinnati

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

Condition or disease
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
Estimated Enrollment : 1000 participants
Observational Model: Ecologic or Community
Time Perspective: Prospective
Official Title: Genetic and Environmental Risk Factors for Hemorrhagic Stroke
Study Start Date : September 1997
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


Group/Cohort
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
whole blood DNA, RNA and Complete Blood Count (CBC)


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
This study will be limited to physician-reviewed cases of people who have had a hemorrhagic stroke.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00682695


Contacts
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Contact: Lee A Gilkerson, RN, BSN 513-558-6140 Lee.gilkerson@uc.edu

Locations
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United States, Illinois
University of Illinois Chicago Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: Maureen Hillman    312-355-3863    hillmann@uic.edu   
Principal Investigator: Fernando Testai, M.D.         
United States, Kentucky
Baptist Health Louisville Recruiting
Louisville, Kentucky, United States, 40207
Contact: Karin Cryan    502-259-5564    karin.cryan@BHSI.COM   
Principal Investigator: Ranjit Bagga, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Tiffany Watson    410-706-1902    tiwatson@som.umaryland.edu   
Principal Investigator: Steven Kittner, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Christina Kourkoulis    617-726-5358    CKOURKOULIS@PARTNERS.ORG   
Principal Investigator: Jonathan R, MD         
United States, New York
Columbia University Not yet recruiting
New York, New York, United States, 10032
Contact: Angela Velazquez    212-305-6071    aqv2113@cumc.columbia.edu   
Principal Investigator: David Roh, M.D.         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Andreea Podgoreanu    919-681-4054    andrea.podgoreanu@duke.edu   
Principal Investigator: Michael L James, MD         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Lee A Gilkerson, RN, BSN    513-558-6140    Lee.gilkerson@uc.edu   
Principal Investigator: Daniel Woo, MD         
Sponsors and Collaborators
University of Cincinnati
National Institute of Neurological Disorders and Stroke (NINDS)
University of Maryland, Baltimore
Massachusetts General Hospital
Duke University, Durham, NC
Columbia University
University of Illinois at Chicago
Baptist Health, Louisville
Investigators
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Principal Investigator: Daniel Woo, MD University of Cincinnati
Publications:

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Responsible Party: Daniel Woo, Professor, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00682695    
Other Study ID Numbers: NS36695
2U01NS036695-15A1 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2008    Key Record Dates
Last Update Posted: February 23, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniel Woo, University of Cincinnati:
stroke
brain attack
hemorrhagic stroke
risk factors
Additional relevant MeSH terms:
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Stroke
Hemorrhagic Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases