Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier:
NCT02055209
First received: February 4, 2014
Last updated: July 10, 2014
Last verified: November 2013
  Purpose

Our objective is to develop a community-based cohort and novel genomic science resource for defining the biological significance of ancestry-related genomic variation in African-Americans within the G EN omics, Environmental FactORs and the Social DE terminants of Cardiovascular Disease in Africans Americans ST udy (GENE-FORECAST ). This resource will enable our team to test the working hypothesis that race-ancestry differences in the burden of cardiovascular disease (CVD) reflects the influence of a unique interplay between the distinct genomic variation characteristic of African-Americans (AA) and the exposome of social determinants and environmental factors that influence the pathogenesis of CVD in AA. The specific aims are:

AIM I. To examine the associations between common or ancestry-related DNA variants and CVD risk factors (e.g. hypertension) and phenotypes (e.g. coronary artery calcification) in African-Americans (AA).

AIM II. To examine the associations between health behaviors or social-environmental factors and CVD risk factors and phenotypes in AA.

The study is designed to create a cohort amenable to nested case-control analyses based on a community-based sampling frame with a target size of approximately 1800 self-identified, U.S. - born, African-American (AA) men and women (ages 21-65) to be recruited over the next 5-6 years from the metropolitan Washington DC, Montgomery County (MC) and Prince George s County (PG) areas. The participant recruitment strategy will involve two complementary approaches: 1) we will contract with a well-established survey group (Southern Research Group) to conduct a random-digit telephone screening survey targeting study-eligible AA that will be consented and invited to an evaluation visit in the NIH Clinical Center; and 2) we will conduct a community outreach effort to recruit participants into the Clinical Center by leveraging the engagement of community-based leaders, organizations and faith-based institutions in the area. Given the high burden of CVD among AA, this approach will yield a sample with normal individuals as well as a high proportion of AA with CVD risk factors such as obesity and hypertension that predispose to the eventual clinical signs and symptoms of CVD (e.g. heart attack and stroke). Based on previous epidemiology studies, this protocol s participant ascertainment approach and the target demographic profile; it is anticipated that the prevalence of clinically manifest CVD (history of angina, heart attack or stroke) will be less than 10-15% of the sample. All participants (either ascertained by random telephone survey or community outreach) will undergo extensive evaluation in the Clinical Center that includes: medical evaluation (e.g. anthropometrics, blood pressure), laboratory tests (e.g. lipid levels, kidney function), social determinants profiles (e.g. socioeconomic status (SES), perceived stress, discrimination, depression, perceived neighborhood characteristics), blood/urine collection for deep-sequencing based omic analyses (whole exome sequencing, and RNA-Seq), as well as testing for pre-clinical , biomarkers of the pathobiological processes of CVD or CVD phenotypes (e.g. coronary artery calcification, microalbuminuria, leukocyte telomeres, or vascular dysfunction). It is anticipated that these deep sequencing efforts will yield novel ancestry-related DNA variants associated with the CVD phenotypes; yet with unclear biological significance in elucidating racial disparities in CVD. Accordingly, our protocol also includes a Genotype-to-Phenotype (G2P) component that re- contacts subsets of the cohort based on their genotype (e.g. APOL1 chronic kidney disease risk alleles) for a call-back visit for more in-depth phenotyping and characterization of the potential effect of the DNA variant of interest on human systems biology. In some cases family members of the proband may also be invited to participate in these G2P studies to further characterize the biological significance of these putative functional DNA variants of interest.

The primary outcome variables involve well established CVD phenotypes: 1) CVD risk factors (e.g. hypertension, dyslipidemia), 2) markers of pre-clinical CVD (i.e. coronary artery calcification, coronary plaque burden by cardiac CT angiography (CTA), carotid plaque burden by 3D ultrasound, vascular dysfunction, microalbuminuria, C-reactive protein, Vitamin D levels). The protocol will assess exposures associated with CVD and relevant covariates including: 1) social determinants (SES, perceived stress, discrimination, and depression); 2) environmental factors such as neighborhood characteristics (geospatial features of healthy lifestyles [e.g. walkability]) and 3) behavioral factors (e.g. diet, physical activity). The G2P call-back visit protocol will involve additional measures of in-depth phenotyping that include: peripheral immune cell phenoty......


Condition
Hypertension
Cardiovascular Disease

Study Type: Observational
Official Title: GENE-FORECASTSM: Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study.

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To develop a novel genomic science resource for defining the functional significance and human biology consequences of ancestry-related genomic variation in AA. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 3341
Study Start Date: January 2014
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Our objective is to develop a community-based cohort and novel genomic science resource for defining the biological significance of ancestry-related genomic variation in African-Americans within GENE-FORECASTSM :GENomics, Environmental FactORs and the Social DEterminants of Cardiovascular Disease in African Americans Study.This resource will enable our team to test the working hypothesis that race-ancestry differences in the burden of cardiovascular disease (CVD) reflects the influence of a unique interplay between the distinct genomic variation characteristic of African-Americans (AA) and the exposome of social determinants and environmental factors that influence the pathogenesis of CVD in AA.

The specific aims are:

AIM I. To examine the associations between common or ancestry-related DNA variants and CVD risk factors (e.g. hypertension) and phenotypes (e.g. coronary artery calcification) in African-Americans (AA).

AIM II. To examine the associations between health behaviors or social-environmental factors and CVD risk factors and phenotypes in AA.

The study is designed to create a cohort amenable to nested case-control analyses based on a community-based sampling frame with a target size of approximately 1800 self-identified, U.S. - born, African-American (AA) men and women (ages 21-65) to be recruited over the next 5-6 years from the metropolitan Washington DC, Montgomery County (MC) and Prince George s County (PG) areas. The participant recruitment strategy will involve two complementary approaches: 1) we will contract with a well-established survey group (Southern Research Group) to conduct a random-digit telephone screening survey targeting study-eligible AA that will be consented and invited to an evaluation visit in the NIH Clinical Center; and 2) we will conduct a community outreach effort to recruit participants into the Clinical Center by leveraging the engagement of community-based leaders, organizations and faith-based institutions in the area. Given the high burden of CVD among AA, this approach will yield a sample with normal individuals as well as a high proportion of AA with CVD risk factors such as obesity and hypertension that predispose to the eventual clinical signs and symptoms of CVD (e.g. heart attack and stroke). Based on previous epidemiology studies, this protocol s participant ascertainment approach and the target demographic profile; it is anticipated that the prevalence of clinically manifest CVD (history of angina, heart attack or stroke) will be less than 10-15% of the sample. All participants (either ascertained by random telephone survey or community outreach) will undergo extensive evaluation in the Clinical Center that includes: medical evaluation (e.g. anthropometrics, blood pressure), laboratory tests (e.g. lipid levels, kidney function), social determinants profiles (e.g. socioeconomic status (SES), perceived stress, discrimination, depression, perceived neighborhood characteristics), blood/urine collection for deep-sequencing based omic analyses (whole exome sequencing, and RNA-Seq), as well as testing for pre-clinical , biomarkers of the pathobiological processes of CVD or CVD phenotypes (e.g. coronary artery calcification, microalbuminuria, leukocyte telomeres, or vascular dysfunction). It is anticipated that these deep sequencing efforts will yield novel ancestry-related DNA variants associated with the CVD phenotypes; yet with unclear biological significance in elucidating racial disparities in CVD. Accordingly, our protocol also includes a Genotype-to-Phenotype (G2P) component that re- contacts subsets of the cohort based on their genotype (e.g. APOL1 chronic kidney disease risk alleles) for a call-back visit for more in-depth phenotyping and characterization of the potential effect of the DNA variant of interest on human systems biology. In some cases family members of the proband may also be invited to participate in these G2P studies to further characterize the biological significance of these putative functional DNA variants of interest.

The primary outcome variables involve well established CVD phenotypes: 1) CVD risk factors (e.g. hypertension, dyslipidemia), 2) markers of pre-clinical CVD (i.e. coronary artery calcification, coronary plaque burden by cardiac CT angiography (CTA), carotid plaque burden by 3D ultrasound, vascular dysfunction, microalbuminuria, C-reactive protein, Vitamin D levels). The protocol will assess exposures associated with CVD and relevant covariates including: 1) social determinants (e.g. socioeconomic status, perceived stress, discrimination, and depression); 2) environmental factors such as neighborhood characteristics (geospatial features of healthy lifestyles [e.g. walkability]) and 3) behavioral factors (e.g. diet, physical activity). The G2P call-back visit protocol will involve additional measures of in-depth phenotyping that include: peripheral immune cell phenotyping (e.g. T-cell, monocyte subsets);1) peripheral immune cell phenotyping (e.g. T-cell, monocyte subsets); 2) blood/immune cell RNA-seq; 3) iPSC cell line generation (endothelial; vascular smooth muscle cells) and analysis of cardiovascular cell systems biology; 4) HDL proteome analysis, 5) FDG PET/CT and/or PET/MRI scan (vascular inflammation); 6) echocardiography; 7) bisulfite sequencing for identifying sites of DNA methylation, and 8) chromatin immunoprecipitation followed by sequencing (Chip-Seq) for identifying sites of histone modification.

It is anticipated that this multi-level, multi-dimensional analysis of genomic and phenotypic characteristics of AA will advance our understanding of the bio-social determinants of the intragroup variance and the increased overall burden of CVD observed among AA.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Community-based self-identified (non-institutionalized), US-born, African American men and women age 21-65 will be included in the study. This criterion is inclusive of self-identified AA of both Hispanic and non-Hispanic ethnicity.

EXCLUSION CRITERIA:

Pregnant women and adults who are unable to provide informed consent will be excluded. Non-English speaking African Americans and those not born in the United States will be excluded. Those with severe and disabling co-morbidities associated with end-stage CVD will be excluded such as a recent history of hospitalization for manifestations of cardiovascular disease. More specifically, patients with a history of stroke, heart attack and/or heart failure in the past 12 months will be excluded. Nursing females will be excluded from FGD PET/CT and/or PET/MRI. Participants with pacemakers and/or any history of metal device implantation and/or metal in their body will be excluded from MRI according to clinical center guidelines. Participants with implanted electronic medical device will be excluded from percent body fat measurement. For CTA, patients with known allergic reaction to contrast will not be given contrast. Diabetic patients taking metformin will be excluded from receiving CTA IV contrast agents. Patients with renal failure (eGFR< 60) will not be given either MRI or CTA IV contrast.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02055209

Contacts
Contact: Laurie-Anne Sayles (301) 451-1905 laurie-anne.sayles@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Gary H Gibbons, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier: NCT02055209     History of Changes
Other Study ID Numbers: 140048, 14-HG-0048
Study First Received: February 4, 2014
Last Updated: July 10, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Coronary Artery Calcification
African American
African-American Families

Additional relevant MeSH terms:
Cardiovascular Diseases
Hypertension
Vascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014