An observational study in Lipid Metabolism Disorders, sponsored by University of Texas Southwestern Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 89 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-20.
Sponsored by University of Texas Southwestern Medical Center · Observational
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.
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.
180 studies on the registry are indexed under Lipid Metabolism Disorders; 33 are open to participants now.
This study's enrollment of 86 is close to the median of 91 across 39 observational studies indexed under Lipid Metabolism Disorders.
Browse Lipid Metabolism Disorders studies →University of Texas Southwestern Medical Center is the lead sponsor of 990 studies on the registry; 201 are open to participants now.
Of its 135 completed or terminated interventional studies of FDA-regulated products, 100 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
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
Exclusion Criteria:
Dallas Heart Study participants who are above the sex and ethnicity specific 90th % of cholesterol efflux
Dallas Heart Study participants who are below the sex and ethnicity specific 10th % of cholesterol efflux
Cholesterol Efflux Capacity (CEC)
Cholesterol efflux capacity (CEC) was determined by measuring the efflux of a fluorophore tagged cholesterol, BODIPY (Avanti polar lipids), from J774 murine macrophages (ATCC) to an appropriate acceptor. Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. Cholesterol efflux capacity is inversely correlated with incidence of cardiovascular events (i.e. higher cholesterol efflux capacity is better for patients).
Time frame: Baseline
Circulating Metabolite (Glucose) Linked to Variation Cholesterol Efflux
The investigators will measure circulating metabolite (glucose) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
Time frame: Baseline
Circulating Metabolite (Creatinine) Linked to Variation Cholesterol Efflux
The investigators will measure circulating metabolite (creatinine) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
Time frame: Baseline
Circulating Proteins Linked to Variation Cholesterol Efflux
The investigators will measure circulating proteins (apolipoprotein A-I, Albumin, Hemoglobin) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
Time frame: Baseline
| Milestone | High Cholesterol Efflux | Low Cholesterol Efflux |
|---|---|---|
| Started | 30 | 27 |
| Completed | 19 | 17 |
| Not completed | 11 | 10 |
Cholesterol efflux capacity (CEC) was determined by measuring the efflux of a fluorophore tagged cholesterol, BODIPY (Avanti polar lipids), from J774 murine macrophages (ATCC) to an appropriate acceptor. Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. Cholesterol efflux capacity is inversely correlated with incidence of cardiovascular events (i.e. higher cholesterol efflux capacity is better for patients).
| Ratio | High Cholesterol Efflux | Low Cholesterol Efflux |
|---|---|---|
| Cholesterol Efflux Capacity (CEC) | 1.30 (1.20 to 1.42) | 0.65 (0.38 to 0.75) |
The investigators will measure circulating metabolite (glucose) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
| mmol/L | High Cholesterol Efflux | Low Cholesterol Efflux |
|---|---|---|
| Circulating Metabolite (Glucose) Linked to Variation Cholesterol Efflux | 5.72 (4.94 to 6.94) | 5.27 (4.99 to 5.77) |
The investigators will measure circulating metabolite (creatinine) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
| umol/L | High Cholesterol Efflux | Low Cholesterol Efflux |
|---|---|---|
| Circulating Metabolite (Creatinine) Linked to Variation Cholesterol Efflux | 77.79 (61.88 to 86.63) | 71.60 (51.27 to 81.33) |
The investigators will measure circulating proteins (apolipoprotein A-I, Albumin, Hemoglobin) and identify the most relevant to the high/low cholesterol efflux phenotype, offering the potential to focus future studies targeting metabolic regulators of efflux.
| G/L | High Cholesterol Efflux | Low Cholesterol Efflux |
|---|---|---|
| Apolipoprotein A-I | 1.54 (1.48 to 1.82) | 1.55 (1.49 to 1.71) |
| Albumin | 44 (42 to 45) | 45 (41 to 46) |
| Hemoglobin | 136 (129 to 149) | 137 (130 to 143) |
Collected over 24 hours from baseline visit. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High Cholesterol Efflux | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) |
| Low Cholesterol Efflux | 0/27 (0%) | 0/27 (0%) | 0/27 (0%) |
| Age, Categorical(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 13 | 4 | 17 |
| >=65 years | 6 | 13 | 19 |
| Sex: Female, Male(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Female | 13 | 12 | 25 |
| Male | 6 | 5 | 11 |
| Race/Ethnicity, Customized(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Black or African American | 12 | 10 | 22 |
| Hispanic or Latino | 9 | 9 | 18 |
| Number of Participants with Hypercholesterolemia(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Count of participants | 9 | 9 | 18 |
| Number of Participants with Diabetes(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Count of participants | 6 | 4 | 10 |
| Number of Participants with Heart Disease(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Count of participants | 2 | 0 | 2 |
| Number of Participants with Hypertension(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Count of participants | 8 | 12 | 20 |
| Number of Participants Menopausal(Participants) | High Cholesterol Efflux | Low Cholesterol Efflux | Total |
|---|---|---|---|
| Count of participants | 11 | 11 | 22 |
5 further baseline measures are reported on the registry.
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This study is completed, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
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University of Texas Southwestern Medical Center