National Heart, Lung, and Blood Institute (NHLBI) — Biomedical Watch V2

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Traitements

8

Molécule	Indication / population	Phase	Objectif	Pays	Résultat
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus ErythematosusStudy Description: Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined. Objectives: Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects: Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects Endpoints: Primary Endpoint: The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects. Exploratory Endpoints: Healthy control vs. SLE subjects: * Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation. * Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates. SLE baseline vs. NR/placebo supplementation: Baseline vs. 6 weeks of NR/placebo: -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils. Baseline vs. 12 weeks of NR/placebo: * Whole blood NAD+ levels (batched and measured at the end of study enrollment period) * Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis. * Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects	Lupus	Phase 1/2	Remyélinisation indirecte / réparation	United States	À vérifier
Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)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 (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 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 (e.g. 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 (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 burde......	Hypertension	À vérifier	Immunomodulation + Traitement symptomatique	United States	À vérifier
Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID)-2.0Background: \- High blood pressure is a common problem. It can cause heart attacks, strokes, and kidney failure. It affects African Americans more than other racial groups. Data were collected from over a thousand African Americans across the country. The data were put into a database (MH-GRID). The data were about genes, diet, sleep, body mass index. They also cover stress and access to healthy foods and parks. Researchers at NIH will study these data in new ways. They want to learn more about the connection between African Americans and high blood pressure. Objective: \- To study MH-GRID data to find the causes of severe high blood pressure and other cardio-metabolic problems in people of African ancestry. Eligibility: \- African Americans age 30 55 with severe high blood pressure were used in the MH-GRID study. No new participants will be enrolled in this study. Design: \- Researchers will examine data from the MH-GRID study.	Hypertension	À vérifier	À vérifier	United States	À vérifier
WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)Background: Williams Syndrome (WS) is a genetic disorder. People with WS have less of a protein that allows parts of the body to stretch than other individuals. Researchers are interested in the stretchiness of the skin of people with WS and how it may relate to cardiovascular problems some people with WS develop. They are also interested in identifying exposures such as medications that may change the elasticity of the skin and vessels. Objective: To learn more about the skin and blood vessels in individuals with WS and how those tissues change over time. Eligibility: People ages 5-70 with WS. People ages 1-70 with a medical condition that affects connective tissue. Design: Participants will be screened with a review of their medical records. Participants will have 1 visit. Participants with WS may do so at a Williams Syndrome Association family meeting or camp, or at NIH. Other participants will be seen at NIH. During the visit, participants will have height, weight, and blood pressure measured. Researchers will listen to the participant s chest and abdomen. Participants skin will be examined. It may be photographed. Participants will have photos of their eyes and face taken. Researchers will use a DermaLab Suction Cup Probe. A small suction cup will be placed on the arm with a sticker. It will pull lightly on the skin. This allows a computer to measure skin flexibility. Researchers will use a SphygmoCor. A probe that looks like a dull pencil will be placed on the wrist, neck, and groin area. A computer will measure how fast the pulse is moving and will estimate blood vessel flexibility. Participants may be invited to have these procedures repeated at a later date (2 years from now or more).	Hypertension	À vérifier	À vérifier	United States	À vérifier
WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)Background: Williams Syndrome (WS) is a genetic disorder. People with WS have less of a protein that allows parts of the body to stretch than other individuals. Researchers are interested in the stretchiness of the skin of people with WS and how it may relate to cardiovascular problems some people with WS develop. They are also interested in identifying exposures such as medications that may change the elasticity of the skin and vessels. Objective: To learn more about the skin and blood vessels in individuals with WS and how those tissues change over time. Eligibility: People ages 5-70 with WS. People ages 1-70 with a medical condition that affects connective tissue. Design: Participants will be screened with a review of their medical records. Participants will have 1 visit. Participants with WS may do so at a Williams Syndrome Association family meeting or camp, or at NIH. Other participants will be seen at NIH. During the visit, participants will have height, weight, and blood pressure measured. Researchers will listen to the participant s chest and abdomen. Participants skin will be examined. It may be photographed. Participants will have photos of their eyes and face taken. Researchers will use a DermaLab Suction Cup Probe. A small suction cup will be placed on the arm with a sticker. It will pull lightly on the skin. This allows a computer to measure skin flexibility. Researchers will use a SphygmoCor. A probe that looks like a dull pencil will be placed on the wrist, neck, and groin area. A computer will measure how fast the pulse is moving and will estimate blood vessel flexibility. Participants may be invited to have these procedures repeated at a later date (2 years from now or more).	Hypertension	À vérifier	À vérifier	United States	À vérifier
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus ErythematosusStudy Description: Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined. Objectives: Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects: Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects Endpoints: Primary Endpoint: The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects. Exploratory Endpoints: Healthy control vs. SLE subjects: * Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation. * Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates. SLE baseline vs. NR/placebo supplementation: Baseline vs. 6 weeks of NR/placebo: -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils. Baseline vs. 12 weeks of NR/placebo: * Whole blood NAD+ levels (batched and measured at the end of study enrollment period) * Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis. * Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects	Lupus	Phase 1/2	Remyélinisation indirecte / réparation	United States	À vérifier
Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)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 (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 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 (e.g. 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 (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 burde......	Hypertension	À vérifier	Immunomodulation + Traitement symptomatique	United States	À vérifier
Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID)-2.0Background: \- High blood pressure is a common problem. It can cause heart attacks, strokes, and kidney failure. It affects African Americans more than other racial groups. Data were collected from over a thousand African Americans across the country. The data were put into a database (MH-GRID). The data were about genes, diet, sleep, body mass index. They also cover stress and access to healthy foods and parks. Researchers at NIH will study these data in new ways. They want to learn more about the connection between African Americans and high blood pressure. Objective: \- To study MH-GRID data to find the causes of severe high blood pressure and other cardio-metabolic problems in people of African ancestry. Eligibility: \- African Americans age 30 55 with severe high blood pressure were used in the MH-GRID study. No new participants will be enrolled in this study. Design: \- Researchers will examine data from the MH-GRID study.	Hypertension	À vérifier	À vérifier	United States	À vérifier

Essais cliniques

4

Molécule	Indication / population	Phase	NCT	Titre	Statut
Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID)-2.0	Hypertension	À vérifier	NCT02290392	Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID)-2.0	COMPLETED
Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)	Hypertension	À vérifier	NCT02055209	Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)	COMPLETED
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus	Lupus	Phase 1/2	NCT06032923	Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus	RECRUITING
WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)	Hypertension	À vérifier	NCT02692846	WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)	COMPLETED

Publications

0

Molécule	Indication / population	Titre	Journal	Date
Aucune publication.