Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02055209 |
| Other study ID # |
140048 |
| Secondary ID |
14-HG-0048 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 23, 2014 |
| Est. completion date |
March 8, 2024 |
Study information
| Verified date |
May 22, 2024 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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 GENE-FORECAST :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, US
-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 to be recruited to the NIH Clinical Center. The initial participant recruitment
strategy involved two approaches: 1) 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 which we contracted with a well-established survey group (Southern Research
Group [SRG]); and 2) a community outreach effort to recruit participants into the Clinical
Center by leveraging marketing and the engagement of community-based leaders, organizations
and faith-based institutions in the area. We are no longer contracting with SRG but rather
focusing on community outreach and marketing for recruitment to the Clinical Center. The
contract with SRG was terminated after the first two years of the protocol due to low yield
of recruitment to the Clinical Center compared to community outreach.
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 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
(e.g. 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 (SES), perceived stress,
discrimination, and depression); 2) environmental factors s...
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 the GENE-FORECAST :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, US
-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 to be recruited to the NIH Clinical Center. The initial participant recruitment
strategy involved two approaches: 1) 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 which we contracted with a well-established survey group (Southern Research
Group [SRG]); and 2) a community outreach effort to recruit participants into the Clinical
Center by leveraging marketing and the engagement of community-based leaders, organizations
and faith-based institutions in the area. We are no longer contracting with SRG but rather
focusing on community outreach and marketing for recruitment to the Clinical Center. The
contract with SRG was terminated after the first two years of the protocol due to low yield
of recruitment to the Clinical Center compared to community outreach.
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 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
(e.g. 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 (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 callback visit protocol will
involve additional measures of in-depth phenotyping that include: 1) peripheral immune cell
phenotyping (e.g. T-cell, monocyte subsets); 2) blood/immune cell RNAseq; 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.
