Ignite Creation Date:
2024-05-06 @ 2:30 AM
Last Modification Date:
2024-10-26 @ 11:19 AM
Study NCT ID:
NCT02055209
Status:
COMPLETED
Last Update Posted:
2024-07-15
First Post:
2014-02-04
Brief Title:
Genomics Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study GENE-FORECAST
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Genomics Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study GENE-FORECAST
Status:
COMPLETED
Status Verified Date:
2024-09-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 AIM I examine the associations between common or ancestry-related DNA variants and CVD risk factors eg hypertension and phenotypes eg coronary artery calcification in African-Americans AAAIM II To examine the associations between health behaviors or social-environmental factors and CVD risk factors and phenotypes in AAThe 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 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 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 eg heart attack and stroke 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 will medical evaluation eg anthropometrics blood pressure laboratory tests eg lipid levels kidney function social determinants profiles eg socioeconomic status SES perceived stress discrimination depression perceived neighborhood characteristics bloodurine collection for deep-sequencing based omic analyses eg whole exome sequencing and RNA-Seq as well as testing for pre-clinical biomarkers of the pathobiological processes of CVD or CVD phenotypes eg 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 eg 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 eg hypertension dyslipidemia 2 markers of pre-clinical CVD ie 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 eg socioeconomic status SES perceived stress discrimination and depression 2 environmental factors such as neighborhood characteristics geospatial features of healthy lifestyles eg walkability and 3 behavioral factors eg diet physical activity The G2P callback visit protocol will involve additional measures of in-depth phenotyping that include 1 peripheral immune cell phenotyping eg T-cell monocyte subsets 2 bloodimmune 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 PETCT andor PETMRI 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 burde
The primary outcome variables involve well established CVD phenotypes 1 CVD risk factors eg hypertension dyslipidemia 2 markers of pre-clinical CVD ie 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 eg socioeconomic status SES perceived stress discrimination and depression 2 environmental factors such as neighborhood characteristics geospatial features of healthy lifestyles eg walkability and 3 behavioral factors eg diet physical activity The G2P callback visit protocol will involve additional measures of in-depth phenotyping that include 1 peripheral immune cell phenotyping eg T-cell monocyte subsets 2 bloodimmune 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 PETCT andor PETMRI 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 burde
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 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 eg hypertension and phenotypes eg 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 eg 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 eg anthropometrics blood pressure laboratory tests eg lipid levels kidney function social determinants profiles eg socioeconomic status SES perceived stress discrimination depression perceived neighborhood characteristics bloodurine collection for deep-sequencing based omic analyses eg whole exome sequencing and RNA-Seq as well as testing for pre-clinical biomarkers of the pathobiological processes of CVD or CVD phenotypes eg 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 eg 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 eg hypertension dyslipidemia 2 markers of pre-clinical CVD ie 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 eg socioeconomic status SES perceived stress discrimination and depression 2 environmental factors such as neighborhood characteristics geospatial features of healthy lifestyles eg walkability and 3 behavioral factors eg diet physical activity The G2P callback visit protocol will involve additional measures of in-depth phenotyping that include 1 peripheral immune cell phenotyping eg T-cell monocyte subsets 2 bloodimmune 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 PETCT andor PETMRI 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
AIM I To examine the associations between common or ancestry-related DNA variants and CVD risk factors eg hypertension and phenotypes eg 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 eg 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 eg anthropometrics blood pressure laboratory tests eg lipid levels kidney function social determinants profiles eg socioeconomic status SES perceived stress discrimination depression perceived neighborhood characteristics bloodurine collection for deep-sequencing based omic analyses eg whole exome sequencing and RNA-Seq as well as testing for pre-clinical biomarkers of the pathobiological processes of CVD or CVD phenotypes eg 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 eg 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 eg hypertension dyslipidemia 2 markers of pre-clinical CVD ie 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 eg socioeconomic status SES perceived stress discrimination and depression 2 environmental factors such as neighborhood characteristics geospatial features of healthy lifestyles eg walkability and 3 behavioral factors eg diet physical activity The G2P callback visit protocol will involve additional measures of in-depth phenotyping that include 1 peripheral immune cell phenotyping eg T-cell monocyte subsets 2 bloodimmune 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 PETCT andor PETMRI 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14-HG-0048 | None | None | None |