Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)

December 6, 2023 updated by: Daniel Woo, University of Cincinnati
The purpose of this study is to find risk factors for hemorrhagic stroke.

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Chicago
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Health Louisville
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Ongoing to be completed at the end of June 2021

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Ongoing to be completed at the end of June 2021

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cincinnati

Collaborators

Massachusetts General Hospital
University of Maryland, Baltimore
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)
University of Illinois at Chicago
Baptist Health, Louisville
Duke University, Durham, NC

Investigators

  • Principal Investigator: Daniel Woo, MD, University of Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1997

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

May 20, 2008

First Submitted That Met QC Criteria

May 20, 2008

First Posted (Estimated)

May 22, 2008

Study Record Updates

Last Update Posted (Estimated)

December 7, 2023

Last Update Submitted That Met QC Criteria

December 6, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NS36695
  • 2U01NS036695-15A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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