HIVHIV RCTSNCT01670968
HIV Reverse Cholesterol Transport Study
An observational study of HIV and Dyslipidemia, run by University College Dublin at 1 site in United Kingdom.
Trial summary
Primary Objective: To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens Secondary Objective: To examine changes in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Dyslipidemia
- How many people
- 100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2009to Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals starting antiretroviral therapy at the Mater Misericordiae University Hospital, Dublin, and Chelsea and Westminister Hospital, London
Who may be able to join
- > 18 years old
- HIV-infected
- Not currently on antiretroviral therapy (>6/12), but about to start
Who cannot join
- On lipid lowering medication (statin / fibrate / niacin)
- HCV Ab+
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Chelsea & Westminster Hospital
London, SW10 9NH
Anton Pozniak, +44 20 8746 8000, anton.pozniak@chelwest.nhs.uk
Graeme Moyle, +44 20 8746 8000, gm@moyleg.demon.co.uk
About this study
Official title: The Effect of Antiretroviral Therapy and HIV on Reverse Cholesterol Transport in Blood( HIV Reverse Cholesterol Transport Study- HIV RCTS)
Primary Objective:
To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens
Secondary Objective:
To examine changes in monocyte intracellular cholesterol content in HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens
Read the detailed description
HIV infection is associated with low HDL-cholesterol, an independent risk-factor for cardiovascular disease (CVD). NNRTI-based HAART increases HDL-c, with nevirapine shown to increase production of its major apolipoprotein ApoA-I. In contrast, initiation of PI-based HAART leads to persistently low HDL-c despite a reduction in HIV RNA and immunologic recovery.
HDL-c is formed through reverse cholesterol transport (RCT), the process where cholesterol is transferred from intracellular pools to circulating lipoproteins which are then eliminated by the liver. Accumulation of intracellular cholesterol in cells such as macrophages and their precursor (circulating monocytes) has been implicated in atherogenesis.
In vitro data suggests the HIV protein Nef directly interferes with cellular proteins involved in RCT such as ATP-binding cassette transporter A1 (ABCA1) in monocyte-derived macrophages. ABCA1 expression is controlled by peroxisome proliferator-activated receptor gamma (PPARG) and the intracellular cholesterol sensor sterol regulatory element binding protein 2 (SREBP2). In adipose tissue it is known that PI treatment downregulates SREBP and PPARG expression.
Preliminary work in the investigators lab has reproduced these findings in monocytes in untreated HIV infection in vivo and demonstrated relationships between gene expression for ABCA1, SREBP2, monocyte intracellular cholesterol and circulating lipoproteins. These early data suggest that defects in RCT determine intracellular cholesterol levels in HIV-infected subjects whereas increased LDL-c is a greater determinant of intracellular cholesterol in HIV negative subjects. This suggests a potentially pivotal role for RCT abnormalities in low HDL-c, increased intracellular cholesterol and atherogenesis in HIV infection.
The investigator's aim to examine the impact of initiation of ART with either PI or NNRTI on RCT in circulating monocytes in vivo and how this impact correlates with changes in amount and size of circulating HDL-c.
- Conditions
- HIV, Dyslipidemia
- Medical subject headings
- Dyslipidemias
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ABCA1 mRNA expression in monocytes
Measured: June 2013
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2012 (estimated)
- Study startSep 2009
- Primary completionMay 2020 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College Dublin
- Sponsor type
- University, hospital or other
- Collaborators
- Chelsea and Westminster NHS Foundation Trust
- Responsible party
- Principal investigator, Patrick Mallon, University College Dublin
- Investigators
- Patrick WG Mallon, FRACP FRCPI PhD, Principal investigator, HIV Molecular Research Group, UCD School of Medicine and Medical Sciences. Department of Infectious Diseases, Mater Misericordiae University Hospital and Mater Private Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01670968
- Sponsor's protocol ID
- HIV RCTS
- Acronym
- HIV RCTS
- Status last verified
- Mar 2020
- First submitted
- 18 Aug 2012
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Antiretroviral Therapy and HIV on Reverse Cholesterol Transport in Blood( HIV Reverse Cholesterol Transport Study- HIV RCTS)
- ClinicalTrials.gov ID
- NCT01670968
- Acronym / sponsor ID
- HIV RCTS / HIV RCTS
- Conditions
- HIV, Dyslipidemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University College DublinUniversity, hospital or other
- Collaborators
- Chelsea and Westminster NHS Foundation Trust
- Study start
- Sep 2009
- Primary completion
- May 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 23 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens
Secondary Objective:
To examine changes in monocyte intracellular cholesterol content in HIV-infected subjects starting antiretroviral therapy and the different effect of NNRTI and PI based regimens
Detailed description
HIV infection is associated with low HDL-cholesterol, an independent risk-factor for cardiovascular disease (CVD). NNRTI-based HAART increases HDL-c, with nevirapine shown to increase production of its major apolipoprotein ApoA-I. In contrast, initiation of PI-based HAART leads to persistently low HDL-c despite a reduction in HIV RNA and immunologic recovery.
HDL-c is formed through reverse cholesterol transport (RCT), the process where cholesterol is transferred from intracellular pools to circulating lipoproteins which are then eliminated by the liver. Accumulation of intracellular cholesterol in cells such as macrophages and their precursor (circulating monocytes) has been implicated in atherogenesis.
In vitro data suggests the HIV protein Nef directly interferes with cellular proteins involved in RCT such as ATP-binding cassette transporter A1 (ABCA1) in monocyte-derived macrophages. ABCA1 expression is controlled by peroxisome proliferator-activated receptor gamma (PPARG) and the intracellular cholesterol sensor sterol regulatory element binding protein 2 (SREBP2). In adipose tissue it is known that PI treatment downregulates SREBP and PPARG expression.
Preliminary work in the investigators lab has reproduced these findings in monocytes in untreated HIV infection in vivo and demonstrated relationships between gene expression for ABCA1, SREBP2, monocyte intracellular cholesterol and circulating lipoproteins. These early data suggest that defects in RCT determine intracellular cholesterol levels in HIV-infected subjects whereas increased LDL-c is a greater determinant of intracellular cholesterol in HIV negative subjects. This suggests a potentially pivotal role for RCT abnormalities in low HDL-c, increased intracellular cholesterol and atherogenesis in HIV infection.
The investigator's aim to examine the impact of initiation of ART with either PI or NNRTI on RCT in circulating monocytes in vivo and how this impact correlates with changes in amount and size of circulating HDL-c.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals starting antiretroviral therapy at the Mater Misericordiae University Hospital, Dublin, and Chelsea and Westminister Hospital, London
Key inclusion criteria (3 listed)
- > 18 years old
- HIV-infected
- Not currently on antiretroviral therapy (>6/12), but about to start
Key exclusion criteria (2 listed)
- On lipid lowering medication (statin / fibrate / niacin)
- HCV Ab+
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
Change in ABCA1 mRNA expression in monocytes
Time frame: June 2013
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
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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.
Patrick WG Mallon, FRACP FRCPI PhD principal investigator
HIV Molecular Research Group, UCD School of Medicine and Medical Sciences. Department of Infectious Diseases, Mater Misericordiae University Hospital and Mater Private Hospital
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 HIV and Dyslipidemia, run by University College Dublin at 1 site in United Kingdom.
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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 25 Mar 2020. 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 Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrick WG Mallon, MB BCh FRACP FRCPI PhD (+353 716 6311, paddy.mallon@ucd.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ABCA1 mRNA expression in monocytes (time frame: June 2013). 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 25 Mar 2020.