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Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)

This study is currently recruiting participants.
Verified July 2017 by Daniel Woo, University of Cincinnati
Sponsor:
ClinicalTrials.gov Identifier:
NCT00682695
First Posted: May 22, 2008
Last Update Posted: July 21, 2017
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.
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Maryland
Massachusetts General Hospital
Duke University, Durham, NC
Information provided by (Responsible Party):
Daniel Woo, University of Cincinnati
  Purpose
The purpose of this study is to find risk factors for hemorrhagic stroke.

Condition
Stroke

Study Type: Observational
Study Design: Observational Model: Ecologic or Community
Time Perspective: Prospective
Official Title: Genetic and Environmental Risk Factors for Hemorrhagic Stroke

Further study details as provided by Daniel Woo, University of Cincinnati:

Primary Outcome Measures:
  • 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. [ Time Frame: Ongoing to be completed at the end of June 2021 ]

Secondary Outcome Measures:
  • Collect and analyze 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. [ Time Frame: Ongoing to be completed at the end of June 2021 ]

Biospecimen Retention:   Samples With DNA
whole blood DNA, RNA and CBA

Estimated Enrollment: 1000
Study Start Date: September 1997
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Healthy volunteers and people who have had a hemorrhagic stroke and live within University of Maryland, University of Cincinnati, Massachusetts General Hospital and Duke University area

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 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 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 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 and who live within a 50-mile radius of Cincinnati, Ohio.
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:

  Contacts and Locations
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
Contact: Jennifer Osborne, RN, MSN 513-558-4241 jennifer.osborne@uc.edu

Locations
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Tiffany Watson    410-706-1902    tiwatson@som.umaryland.edu   
Sub-Investigator: Steven Kittner, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Christina Kourkoulis    617-726-5358      
Sub-Investigator: Jonathan R, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Erlinda Yeh    919-681-4054    linda.yeh@duke.edu   
Sub-Investigator: Michael L James, MD         
United States, Ohio
Jennifer Osborne Completed
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
National Institute of Neurological Disorders and Stroke (NINDS)
University of Maryland
Massachusetts General Hospital
Duke University, Durham, NC
Investigators
Principal Investigator: Daniel Woo, MD University of Cincinnati
  More Information

Publications:

Responsible Party: Daniel Woo, Professor, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00682695     History of Changes
Other Study ID Numbers: R01NS036695 ( U.S. NIH Grant/Contract )
First Submitted: May 20, 2008
First Posted: May 22, 2008
Last Update Posted: July 21, 2017
Last Verified: July 2017

Keywords provided by Daniel Woo, University of Cincinnati:
stroke
brain attack
hemorrhagic stroke
risk factors

Additional relevant MeSH terms:
Stroke
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhage
Pathologic Processes