search
Back to results

Contribution of Dolutegravir to Obesity and Cardiovascular Disease

Primary Purpose

HIV-1-infection, Antiviral Drug Adverse Reaction, Vascular Diseases

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dolutegravir 50 MG
Antiretroviral/Anti HIV
Sponsored by
Augusta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for HIV-1-infection

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
  • 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.

Sites / Locations

  • Augusta University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Switch from a non-integrase based regimen to dolutegravir

Continue on non-integrase inhibitor based regimen

Arm Description

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.

Participants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen.

Outcomes

Primary Outcome Measures

Change in Weight
Change from baseline kilograms (kg) of weight at 24 weeks

Secondary Outcome Measures

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)
Change in vascular endothelial function
Change from baseline vessel diameter (millimeters) at 24 weeks
Height
Measurement of height (centimeters) from baseline to 24 weeks

Full Information

First Posted
April 1, 2020
Last Updated
July 25, 2023
Sponsor
Augusta University
search

1. Study Identification

Unique Protocol Identification Number
NCT04340388
Brief Title
Contribution of Dolutegravir to Obesity and Cardiovascular Disease
Official Title
Contribution of the Integrase Inhibitor Dolutegravir to Obesity and Cardiovascular Disease in Persons Living With HIV
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
September 17, 2020 (Actual)
Primary Completion Date
June 17, 2022 (Actual)
Study Completion Date
February 25, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Switch from a non-integrase based regimen to dolutegravir
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Continue on non-integrase inhibitor based regimen
Arm Type
Active Comparator
Arm Description
Participants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen.
Intervention Type
Drug
Intervention Name(s)
Dolutegravir 50 MG
Other Intervention Name(s)
Tenofovir alafenamide, Tenofovir disoproxil fumarate, Abacavir, Lamivudine, Darunavir, Cobicistat, Rilpivirine, Combivir, Zidovudine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Antiretroviral/Anti HIV
Other Intervention Name(s)
Antiretroviral Combinations
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Weight
Description
Change from baseline kilograms (kg) of weight at 24 weeks
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in body mass index (BMI)
Description
Total change in body mass index -height and weight will be combined to report BMI (Kilogram/Height in centimeters^2)
Time Frame
24 weeks
Title
Change in vascular endothelial function
Description
Change from baseline vessel diameter (millimeters) at 24 weeks
Time Frame
24 weeks
Title
Height
Description
Measurement of height (centimeters) from baseline to 24 weeks
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Change in cholesterol
Description
Change from baseline cholesterol (mg/dL) at 24 weeks
Time Frame
24 weeks
Title
Change in triglycerides
Description
Change from baseline triglycerides (mg/dL) at 24 weeks
Time Frame
24 weeks
Title
Change in high density lipoprotein (HDL)
Description
Change from baseline HDL (mg/dL) at 24 weeks
Time Frame
24 weeks
Title
Change in low density lipoprotein (LDL)
Description
Change from baseline LDL (mg/dL) at 24 weeks
Time Frame
24 weeks
Title
Change in HIV-1 RNA viral load
Description
Change from baseline HIV-1 viral load (copies) at 24 weeks
Time Frame
24 weeks
Title
Change in fasting serum glucose level
Description
Change from baseline serum glucose level (mg/dL) at 24 weeks
Time Frame
24 weeks
Title
Change in quantity of food consumption
Description
Change from baseline of calorie consumption (kcal) at 24 weeks
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonell B Poe, MPAS
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
Following publication. No end date.
IPD Sharing Access Criteria
To achieve aims in the approved proposal.
Citations:
PubMed Identifier
23824675
Citation
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.
Results Reference
result

Learn more about this trial

Contribution of Dolutegravir to Obesity and Cardiovascular Disease

We'll reach out to this number within 24 hrs