Lipid Metabolism DisordersNCT04061018
The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux
An observational study of Lipid Metabolism Disorders, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Lipid Metabolism Disorders
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2017to 31 May 2025
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- Dallas Heart Study (DHS) Participants who are above or below the sex- and ethnicity-specific 10th and 90th% of cholesterol efflux.
- Family members of the DHS participants are also eligible
Who cannot join
- HIV
- Cancer
- Autoimmune diseases
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Lipid Metabolism Disorders
- Keywords
- HDL, Atherosclerotic Cardiovascular Disease, Cholesterol efflux
- Medical subject headings
- Lipid Metabolism Disorders, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| High Cholesterol Efflux | Dallas Heart Study participants who are above the sex and ethnicity specific 90th % of cholesterol efflux | |
| Low Cholesterol Efflux | Dallas Heart Study participants who are below the sex and ethnicity specific 10th % of cholesterol efflux |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2019
- Study start1 Dec 2017
- Primary completion1 Dec 2023
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lipid Metabolism DisordersStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Anand Rohatgi, University of Texas Southwestern Medical Center
- Investigators
- Anand Rohatgi, MD, Principal investigator, UT Southwetsern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04061018
- Sponsor's protocol ID
- STU 042016-020
- Other IDs
- 1R01HL136724-01A1
- Status last verified
- Feb 2026
- First submitted
- 26 Jul 2019
- Last updated
- 20 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux
- ClinicalTrials.gov ID
- NCT04061018
- Acronym / sponsor ID
- STU 042016-020
- Conditions
- Lipid Metabolism Disorders
- Keywords
- HDL, Atherosclerotic Cardiovascular Disease, Cholesterol efflux
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 19 Aug 2019 (actual)
- Results
- Posted 20 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Cholesterol Efflux | – | –Dallas Heart Study participants who are above the sex and ethnicity specific 90th % of cholesterol efflux |
| Low Cholesterol Efflux | – | –Dallas Heart Study participants who are below the sex and ethnicity specific 10th % of cholesterol efflux |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (2 listed)
- Dallas Heart Study (DHS) Participants who are above or below the sex- and ethnicity-specific 10th and 90th% of cholesterol efflux.
- Family members of the DHS participants are also eligible
Key exclusion criteria (4 listed)
- HIV
- Cancer
- Autoimmune diseases
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cholesterol Efflux Capacity (CEC)
Time frame: Baseline
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).
Circulating Metabolite (Glucose) Linked to Variation Cholesterol Efflux
Time frame: Baseline
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.
Circulating Metabolite (Creatinine) Linked to Variation Cholesterol Efflux
Time frame: Baseline
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.
Circulating Proteins Linked to Variation Cholesterol Efflux
Time frame: Baseline
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anand Rohatgi, MD principal investigator
UT Southwetsern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lipid Metabolism Disorders, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cholesterol Efflux Capacity (CEC) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.