The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux
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ClinicalTrials.gov Identifier: NCT04061018 |
Recruitment Status :
Active, not recruiting
First Posted : August 19, 2019
Last Update Posted : April 10, 2024
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Tracking Information | |||||
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First Submitted Date | July 26, 2019 | ||||
First Posted Date | August 19, 2019 | ||||
Last Update Posted Date | April 10, 2024 | ||||
Actual Study Start Date | December 1, 2017 | ||||
Actual Primary Completion Date | December 1, 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
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Original Primary Outcome Measures | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures | Not Provided | ||||
Original Secondary Outcome Measures | Not Provided | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux | ||||
Official Title | The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux | ||||
Brief Summary | The rationale of this research is that deep phenotyping of individuals at the extremes of cholesterol efflux will identify key determinants of efflux that are potential novel therapeutic targets to prevent or reverse Atherosclerotic Cardiovascular Disease (ASCVD). The investigators propose to carry out the objective by studying participants at extreme low and high cholesterol efflux identified from the investigator's study in the population-based Dallas Heart Study by accomplishing the following aims: 1) determine the heritability of and genomic factors associated with cholesterol efflux by establishing a family pedigree of extreme low and high efflux and sequencing candidate genes involved in HDL metabolism; and 2) identify the protein and lipid signature of extreme low and high cholesterol efflux in a sex- and ethnicity-specific manner using mass spectroscopy and ELISA in FPLC-derived fractions. The investigators expect to identify genetic variants and sex- and ethnicity-specific combinations of proteins and lipids in participants with extreme low and high efflux that may lead to novel ways to modulate efflux. This proposal leverages a well-phenotyped population-based study to characterize the gene-protein-lipid signature of 1) extremes of cholesterol efflux in a sex- and ethnicity-specific manner. Successful completion of these aims will have immediate and direct impact on the use of cholesterol efflux as a clinically relevant biomarker of therapeutic benefit and are necessary for the clinical development of appropriate new targets for manipulation of the key atheroprotective function of cholesterol efflux to reduce ASCVD. | ||||
Detailed Description | The mechanisms that underlie variation in cholesterol efflux are unknown. There is a critical need to identify factors that regulate cholesterol efflux to effectively advance the clinical development of cholesterol efflux as both a risk prediction marker and as a target of therapy. The investigator's long-term goal is to determine whether modulating cholesterol efflux prevents or reverses cardiovascular disease. The overall objective of this study is to systematically create a family pedigree and biobank repository of blood and DNA from participants from the Dallas Heart Study with extreme low or high cholesterol efflux, with the specific aims of : 1) determining the heritability of and genomic factors associated with cholesterol efflux, and 2) identifying the protein and lipid signature of extreme low and high cholesterol efflux in a sex- and ethnicity-specific manner. The investigator's central hypothesis is that a combination of genetic variation in lipid transporters as well as proteins and lipids will be most strongly correlated with variation in efflux. DHS probands and their relatives (parents, siblings, adult children, grandparents, aunts/uncles, cousins) with extreme low or high cholesterol efflux will be recruited to establish a prospective family pedigree cohort and understand the heritability of extreme cholesterol efflux. Investigators will collect the following information from all participants: demographics, health history, lifestyle measures, and medications. Blood will be collected on-site by venipuncture and plasma, serum, and cells will be stored at -80o Celsius. All efflux measurements will be completed in the investigator's laboratory. |
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Study Type | Observational | ||||
Study Design | Observational Model: Cohort Time Perspective: Cross-Sectional |
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Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Retention: Samples With DNA Description: Plasma, Serum, DNA
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Sampling Method | Non-Probability Sample | ||||
Study Population | Participants from the Dallas Heart Study (DHS) with extreme low or high cholesterol efflux will be recruited in this study. DHS is a multi-ethnic, population based probability sample of Dallas County designed to define the social and the biological variables contributing to ethnic differences in cardiovascular health at the community level. https://www.utsouthwestern.edu/edumedia/edufiles/research/center_translational_medicine/dallas_heart_study/dhs-study-overview.pdf |
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Condition | Lipid Metabolism Disorders | ||||
Intervention | Not Provided | ||||
Study Groups/Cohorts |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Active, not recruiting | ||||
Estimated Enrollment |
180 | ||||
Original Estimated Enrollment | Same as current | ||||
Estimated Study Completion Date | May 6, 2025 | ||||
Actual Primary Completion Date | December 1, 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years to 89 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | Yes | ||||
Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT04061018 | ||||
Other Study ID Numbers | STU 042016-020 1R01HL136724-01A1 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement | Not Provided | ||||
Current Responsible Party | Anand Rohatgi, University of Texas Southwestern Medical Center | ||||
Original Responsible Party | University of Texas Southwestern Medical Center | ||||
Current Study Sponsor | University of Texas Southwestern Medical Center | ||||
Original Study Sponsor | Same as current | ||||
Collaborators | National Heart, Lung, and Blood Institute (NHLBI) | ||||
Investigators |
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PRS Account | University of Texas Southwestern Medical Center | ||||
Verification Date | April 2024 |