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

February 4, 2014
July 10, 2014
January 2014
June 2018   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT02055209 on ClinicalTrials.gov Archive Site
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Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)
GENE-FORECASTSM: Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study.

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......

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.

Observational
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  • Hypertension
  • Cardiovascular Disease
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
3341
June 2018
June 2018   (final data collection date for primary outcome measure)
  • 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.

Both
21 Years to 65 Years
Yes
Contact: Laurie-Anne Sayles (301) 451-1905 laurie-anne.sayles@nih.gov
United States
 
NCT02055209
140048, 14-HG-0048
Not Provided
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
National Human Genome Research Institute (NHGRI)
Not Provided
Principal Investigator: Gary H Gibbons, M.D. National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health Clinical Center (CC)
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP