HIV-1-infectionPhase 4NCT04340388
Contribution of Dolutegravir to Obesity and Cardiovascular Disease
A Phase 4 study testing Dolutegravir 50 MG and Antiretroviral/Anti HIV in people with HIV-1-infection and Antiviral Drug Adverse Reaction, run by Augusta University at 1 site in United States.
Trial summary
The goal of the study is to combine a collaborative and translational approach to evaluate the effect antiretroviral regimen switch to a dolutegravir containing regimen compared to continued treatment with a non- dolutegravir based regimen on on lipid and metabolic profiles, renal function, body composition, vascular… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- HIV-1-infection, Antiviral Drug Adverse Reaction, Vascular Diseases
- What is being tested?
- Dolutegravir 50 MG and Antiretroviral/Anti HIV
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Sep 2020to 25 Feb 2023
- Phase
- Phase 4
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet the following criteria to be eligible for participation in this study:
- Age greater than or equal to 18 years with HIV-1 who have been virologically suppressed (HIV-1 RNA < 50 copies for greater than or equal to 3 months on a non-integrase strand transfer inhibitor-based regimen
- Have the ability to understand and sign an informed consent written in the English language
Who cannot join
- Subjects meeting any of the following exclusion criteria are not to be enrolled in this study:
- Age less than 18 years without HIV-1 infection
- Has hypersensitivity or other contraindication to any of the components of the study
- Has active diagnosis of untreated hepatitis due to any cause
- Has a history or current evidence of any condition, laboratory abnormality or other circumstance ( including drug or alcohol use or dependence) that might confound the results of the study or interfere with the subject's participation for the full duration of the study
- Is taking or is anticipated to require long term systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 60 days prior to Screening/Day 1 visit through to the end of study
Show all 10Show fewer
- Has documented or suspected dolutegravir-associated resistance mutations specifically:
- Q148H/K/R/N in combination with E138K or G1402/A or N155H.
- Has a life expectancy less than or equal to one year
- Is pregnant, breastfeeding, or expecting to donate eggs or sperm or conceive or father a child at any time during the study and 6 weeks following the end of study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Contribution of the Integrase Inhibitor Dolutegravir to Obesity and Cardiovascular Disease in Persons Living With HIV
The goal of the study is to combine a collaborative and translational approach to evaluate the effect antiretroviral regimen switch to a dolutegravir containing regimen compared to continued treatment with a non- dolutegravir based regimen on on lipid and metabolic profiles, renal function, body composition, vascular function and diet.
Read the detailed description
Over the last decades, the use of combined antiretroviral therapy has led to profound suppression of HIV-1 replication and increased the survival of persons living with HIV (PLWH) to close to that of the general population. As a consequence, the spectrum of diseases related to HIV has shifted from opportunistic AIDS-related diseases towards long-term-age-related complications. Individuals living with HIV are now exhibiting accelerated development of obesity, metabolic derangements and cardiovascular disease (CVD). Recent compelling clinical evidence has documented a drastic shift in anthropometric profiles among persons living with HIV. In addition, several reports present dolutegravir, a second-generation integrase inhibitor currently highly prescribed for its high antiviral efficiency, as the potential cause of unpredicted weight gain. A critical gap in the investigators' knowledge is a lack of understanding of the etiopathology of the contribution of dolutegravir on weight gain and the consequential impact on obesity and cardiovascular disease in persons living with HIV on combined antiretroviral therapy. As overweight and obesity are among the leading risk factors for cardiovascular disease in persons living with HIV, it is critical to directly investigate whether dolutegravir increases fat mass in persons living with HIV and whether body weight gains-associated with dolutegravir based regimen contribute to the increased prevalence of CVD in this population of people.
This application seeks to investigate alterations in body fat and cardiometabolic risk markers associated with dolutegravir. The investigators propose that in patients with undetectable plasma HIV RNA, there is a direct correlation of weight gain and dolutegravir after antiretroviral regimen switch. They also contend that dolutegravir associated weight gain induces a phenotypic metabolic shift which alters the vascular endothelium and potentiates CVD risk. If the investigators are correct in their hypotheses, modifications in the clinical practice of treatment and prevention strategies for CVD in people living with HIV may be warranted.
Herein the investigators propose a novel translational study which will concomitantly investigate in human patients and animal models of HIV:
- whether dolutegravir based regimen increases body weight
- the mechanisms whereby dolutegravir increases body weight
- whether dolutegravir-mediated body weight gain increases the risk for CVD in PLWH.
- Conditions
- HIV-1-infection, Antiviral Drug Adverse Reaction, Vascular Diseases, Cardiovascular Abnormalities, Abnormality of Adipose Tissue, Body Weight Changes
- Being tested
- Dolutegravir 50 MG, Antiretroviral/Anti HIV
- Medical subject headings
- Vascular Diseases, Cardiovascular Abnormalities, Body Weight Changes, HIV-Associated Lipodystrophy Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir 50 MGDrug
Also called Tenofovir alafenamide, Tenofovir disoproxil fumarate, Abacavir, Lamivudine
15 participants will be randomized to remain on fully suppressive background antiretroviral therapy. The third agent will be switched to dolutegravir at the dose of 50 mg daily.
Antiretroviral/Anti HIVDrug
Also called Antiretroviral Combinations
15 participants with suppressed HIV disease for greater than or equal to 3 months will be randomized to remain on their current 2 or 3 drug fully suppressive antiretroviral regimen.
| Study group | Role | What they receive |
|---|---|---|
| Switch from a non-integrase based regimen to dolutegravir | Active comparator | Participants with HIV-1 infection who have had viral suppression on a non-integrase based antiretroviral regimen for greater than or equal to 3 months will be switched to a dolutegravir based regimen dosed at 50 milligrams (MG) once daily. Background regimen will remain the same. Receives: Drug: Dolutegravir 50 MG |
| Continue on non-integrase inhibitor based regimen | Active comparator | Participants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen. Receives: Drug: Antiretroviral/Anti HIV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Weight
Change from baseline kilograms (kg) of weight at 24 weeks
Measured: 24 weeks
Secondary outcomes (3)
Change in body mass index (BMI)
Total change in body mass index -height and weight will be combined to report BMI (Kilogram/Height in centimeters^2)
Measured: 24 weeks
Change in vascular endothelial function
Change from baseline vessel diameter (millimeters) at 24 weeks
Measured: 24 weeks
Height
Measurement of height (centimeters) from baseline to 24 weeks
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start17 Sep 2020
- Primary completion17 Jun 2022
- Study completion25 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study design is a randomized control trial where patients will be randomized to the dolutegravir or non-dolutegravir arms by random number generation using the statistical software R. A unique identification (ID) key from 1 to 2n will be assigned to each patient. Additionally, the investigators will utilize a parallel mouse model of HIV mimicking PLWH with stable viral load that can provide mechanistic insight and integrate experiments at the tissue level (adipose tissue) as well. Experiments in the parallel mouse model of HIV will also present the advantage to enable the study the direct effects of HIV viral infection on metabolic and cardiovascular function, a study not feasible in PWH who, for easily understandable ethical reasons, cannot remain without treatment for 6 months (duration of the study).
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonell Poe, Augusta University
- Investigators
- Jonell B Poe, MPAS, Principal investigator, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04340388
- Sponsor's protocol ID
- 1553691-1
- Status last verified
- Jul 2023
- First submitted
- 1 Apr 2020
- Last updated
- 27 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators plan to share de-identified all IPD included in this study and that de-identified IPD results that underlie applications for additional funding or for publication.
Publications
Cottrell ML, Hadzic T, Kashuba AD. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2.
PubMed 23824675
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of the Integrase Inhibitor Dolutegravir to Obesity and Cardiovascular Disease in Persons Living With HIV
- ClinicalTrials.gov ID
- NCT04340388
- Acronym / sponsor ID
- 1553691-1
- Conditions
- HIV-1-infection, Antiviral Drug Adverse Reaction, Vascular Diseases, Cardiovascular Abnormalities, Abnormality of Adipose Tissue, Body Weight Changes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Study start
- 17 Sep 2020 (actual)
- Primary completion
- 17 Jun 2022 (actual)
- Study completion
- 25 Feb 2023 (actual)
- First posted
- 9 Apr 2020 (actual)
- 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.
The goal of the study is to combine a collaborative and translational approach to evaluate the effect antiretroviral regimen switch to a dolutegravir containing regimen compared to continued treatment with a non- dolutegravir based regimen on on lipid and metabolic profiles, renal function, body composition, vascular function and diet.
Detailed description
Over the last decades, the use of combined antiretroviral therapy has led to profound suppression of HIV-1 replication and increased the survival of persons living with HIV (PLWH) to close to that of the general population. As a consequence, the spectrum of diseases related to HIV has shifted from opportunistic AIDS-related diseases towards long-term-age-related complications. Individuals living with HIV are now exhibiting accelerated development of obesity, metabolic derangements and cardiovascular disease (CVD). Recent compelling clinical evidence has documented a drastic shift in anthropometric profiles among persons living with HIV. In addition, several reports present dolutegravir, a second-generation integrase inhibitor currently highly prescribed for its high antiviral efficiency, as the potential cause of unpredicted weight gain. A critical gap in the investigators' knowledge is a lack of understanding of the etiopathology of the contribution of dolutegravir on weight gain and the consequential impact on obesity and cardiovascular disease in persons living with HIV on combined antiretroviral therapy. As overweight and obesity are among the leading risk factors for cardiovascular disease in persons living with HIV, it is critical to directly investigate whether dolutegravir increases fat mass in persons living with HIV and whether body weight gains-associated with dolutegravir based regimen contribute to the increased prevalence of CVD in this population of people.
This application seeks to investigate alterations in body fat and cardiometabolic risk markers associated with dolutegravir. The investigators propose that in patients with undetectable plasma HIV RNA, there is a direct correlation of weight gain and dolutegravir after antiretroviral regimen switch. They also contend that dolutegravir associated weight gain induces a phenotypic metabolic shift which alters the vascular endothelium and potentiates CVD risk. If the investigators are correct in their hypotheses, modifications in the clinical practice of treatment and prevention strategies for CVD in people living with HIV may be warranted.
Herein the investigators propose a novel translational study which will concomitantly investigate in human patients and animal models of HIV:
- whether dolutegravir based regimen increases body weight
- the mechanisms whereby dolutegravir increases body weight
- whether dolutegravir-mediated body weight gain increases the risk for CVD in PLWH.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study design is a randomized control trial where patients will be randomized to the dolutegravir or non-dolutegravir arms by random number generation using the statistical software R. A unique identification (ID) key from 1 to 2n will be assigned to each patient. Additionally, the investigators will utilize a parallel mouse model of HIV mimicking PLWH with stable viral load that can provide mechanistic insight and integrate experiments at the tissue level (adipose tissue) as well. Experiments in the parallel mouse model of HIV will also present the advantage to enable the study the direct effects of HIV viral infection on metabolic and cardiovascular function, a study not feasible in PWH who, for easily understandable ethical reasons, cannot remain without treatment for 6 months (duration of the study).
| Arm | Type | Receives |
|---|---|---|
| Switch from a non-integrase based regimen to dolutegravir | Active comparator | Drug: Dolutegravir 50 MGParticipants with HIV-1 infection who have had viral suppression on a non-integrase based antiretroviral regimen for greater than or equal to 3 months will be switched to a dolutegravir based regimen dosed at 50 milligrams (MG) once daily. Background regimen will remain the same. |
| Continue on non-integrase inhibitor based regimen | Active comparator | Drug: Antiretroviral/Anti HIVParticipants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age greater than or equal to 18 years with HIV-1 who have been virologically suppressed (HIV-1 RNA < 50 copies for greater than or equal to 3 months on a non-integrase strand transfer inhibitor-based regimen
- Have the ability to understand and sign an informed consent written in the English language
Key exclusion criteria (10 listed)
- Subjects meeting any of the following exclusion criteria are not to be enrolled in this study:
- Age less than 18 years without HIV-1 infection
- Has hypersensitivity or other contraindication to any of the components of the study
- Has active diagnosis of untreated hepatitis due to any cause
- Has a history or current evidence of any condition, laboratory abnormality or other circumstance ( including drug or alcohol use or dependence) that might confound the results of the study or interfere with the subject's participation for the full duration of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dolutegravir 50 MGAlso: Tenofovir alafenamide, Tenofovir disoproxil fumarate, Abacavir, Lamivudine15 participants will be randomized to remain on fully suppressive background antiretroviral therapy. The third agent will be switched to dolutegravir at the dose of 50 mg daily. | Drug | Switch from a non-integrase based regimen to dolutegravir |
| Antiretroviral/Anti HIVAlso: Antiretroviral Combinations15 participants with suppressed HIV disease for greater than or equal to 3 months will be randomized to remain on their current 2 or 3 drug fully suppressive antiretroviral regimen. | Drug | Continue on non-integrase inhibitor based regimen |
Primary outcome
Change in Weight
Time frame: 24 weeks
Change from baseline kilograms (kg) of weight at 24 weeks
3 secondary outcomes
Change in body mass index (BMI)
Time frame: 24 weeks
Change in vascular endothelial function
Time frame: 24 weeks
Height
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Results publication: PubMed 23824675Cottrell ML, Hadzic T, Kashuba AD. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2.
- Individual participant dataSharing planned: Yes. The investigators plan to share de-identified all IPD included in this study and that de-identified IPD results that underlie applications for additional funding or for publication.
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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.
Jonell B Poe, MPAS principal investigator
Augusta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dolutegravir 50 MG and Antiretroviral/Anti HIV in people with HIV-1-infection and Antiviral Drug Adverse Reaction, run by Augusta University 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 3 inclusion and 10 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 27 Jul 2023. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Weight (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04340388, which also lists 1 linked publication.
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 27 Jul 2023; AzTrials last refreshed its copy on 8 Nov 2026.