Contribution of Dolutegravir to Obesity and Cardiovascular Disease
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|ClinicalTrials.gov Identifier: NCT04340388|
Recruitment Status : Not yet recruiting
First Posted : April 9, 2020
Last Update Posted : April 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|HIV-1-infection Antiviral Drug Adverse Reaction Vascular Diseases Cardiovascular Abnormalities Abnormality of Adipose Tissue Body Weight Changes Body Fat Disorder HIV-Associated Lipodystrophy Syndrome||Drug: Dolutegravir 50 MG Drug: Antiretroviral/Anti HIV||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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)|
|Primary Purpose:||Basic Science|
|Official Title:||Contribution of the Integrase Inhibitor Dolutegravir to Obesity and Cardiovascular Disease in Persons Living With HIV|
|Estimated Study Start Date :||June 2020|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||March 2021|
Active Comparator: Switch from a non-integrase based regimen to dolutegravir
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.
Drug: Dolutegravir 50 MG
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.
Active Comparator: Continue on non-integrase inhibitor based regimen
Participants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen.
Drug: Antiretroviral/Anti HIV
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.
Other Name: Antiretroviral Combinations
- Change in Weight [ Time Frame: 24 weeks ]Change from baseline kilograms (kg) of weight at 24 weeks
- Change in body mass index (BMI) [ Time Frame: 24 weeks ]Total change in body mass index -height and weight will be combined to report BMI (Kilogram/Height in centimeters^2)
- Change in vascular endothelial function [ Time Frame: 24 weeks ]Change from baseline vessel diameter (millimeters) at 24 weeks
- Height [ Time Frame: 24 weeks ]Measurement of height (centimeters) from baseline to 24 weeks
- Change in cholesterol [ Time Frame: 24 weeks ]Change from baseline cholesterol (mg/dL) at 24 weeks
- Change in triglycerides [ Time Frame: 24 weeks ]Change from baseline triglycerides (mg/dL) at 24 weeks
- Change in high density lipoprotein (HDL) [ Time Frame: 24 weeks ]Change from baseline HDL (mg/dL) at 24 weeks
- Change in low density lipoprotein (LDL) [ Time Frame: 24 weeks ]Change from baseline LDL (mg/dL) at 24 weeks
- Change in HIV-1 RNA viral load [ Time Frame: 24 weeks ]Change from baseline HIV-1 viral load (copies) at 24 weeks
- Change in fasting serum glucose level [ Time Frame: 24 weeks ]Change from baseline serum glucose level (mg/dL) at 24 weeks
- Change in quantity of food consumption [ Time Frame: 24 weeks ]Change from baseline of calorie consumption (kcal) at 24 weeks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04340388
|Contact: Ivy Tillmanemail@example.com|
|Contact: Martha Farrough, RNfirstname.lastname@example.org|
|Principal Investigator:||Jonell B Poe, MPAS||Augusta University|