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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04340388
Other study ID # 1553691-1
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
Start date September 17, 2020
Est. completion date February 25, 2023

Study information

Verified date July 2023
Source Augusta University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 function and diet.


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: 1. whether dolutegravir based regimen increases body weight 2. the mechanisms whereby dolutegravir increases body weight 3. whether dolutegravir-mediated body weight gain increases the risk for CVD in PLWH.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date February 25, 2023
Est. primary completion date June 17, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility 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.

Study Design


Intervention

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.
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.

Locations

Country Name City State
United States Augusta University Augusta Georgia

Sponsors (1)

Lead Sponsor Collaborator
Augusta University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Change in cholesterol Change from baseline cholesterol (mg/dL) at 24 weeks 24 weeks
Other Change in triglycerides Change from baseline triglycerides (mg/dL) at 24 weeks 24 weeks
Other Change in high density lipoprotein (HDL) Change from baseline HDL (mg/dL) at 24 weeks 24 weeks
Other Change in low density lipoprotein (LDL) Change from baseline LDL (mg/dL) at 24 weeks 24 weeks
Other Change in HIV-1 RNA viral load Change from baseline HIV-1 viral load (copies) at 24 weeks 24 weeks
Other Change in fasting serum glucose level Change from baseline serum glucose level (mg/dL) at 24 weeks 24 weeks
Other Change in quantity of food consumption Change from baseline of calorie consumption (kcal) at 24 weeks 24 weeks
Primary Change in Weight Change from baseline kilograms (kg) of weight at 24 weeks 24 weeks
Secondary 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) 24 weeks
Secondary Change in vascular endothelial function Change from baseline vessel diameter (millimeters) at 24 weeks 24 weeks
Secondary Height Measurement of height (centimeters) from baseline to 24 weeks 24 weeks
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