Early Metabolic Effects of Dolutegravir or Tenofovir Alefenamide in Healthy Volunteers

Healthy Volunteer Clinical Trial

Official title: A Phase 2 Randomized Cross-Over Design Study of the Early Metabolic Effects of Dolutegravir or Tenofovir Alafenamide in Healthy Volunteers

Status Not yet recruiting

Clinical Trial Summary

Background:

People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes.

Objective:

To see how a common INSTI, dolutegravir (DTG), affects how the body uses energy. DTG will be compared with a non-INSTI drug, tenofovir alafenamide (TAF).

Eligibility:

Healthy people aged 18 to 55.

Design:

Participants will be screened. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.

Participants will have 2 inpatient stays at the clinic. Each stay will be for 11 nights, with a 3-week break between.

Both DTG and TAF are gel caps swallowed once per day by mouth. Participants will take 1 drug for 8 days during each stay.

Participants will have tests to see how their body uses energy:

They will spend 23 continuous hours in a special room that measures how much oxygen they breathe in and how much carbon dioxide they breathe out. They will do this a total of 6 times.

They will have a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density.

They will lie on a table. Electrodes will be placed on their hands and feet to measure body fat and lean body mass.

They will stand still on a platform for about 30 seconds. High-resolution laser cameras will scan their bodies.

Clinical Trial Description

Study Description:

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral (ARV) drugs currently included in first-line therapy to treat HIV infection. Several observational trials have shown that one side effect of this class of ARVs is involuntary weight gain. How these drugs cause weight gain is unknown. In addition, these marketed drugs are formulated in combination with the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir alafenamide (TAF), which may also independently contribute to weight gain, as compared to the older formulation of tenofovir disoproxil fumarate (TDF). To better understand the effects of INSTIs and TAF on metabolism, participants will be randomized 1:1 to either the INSTI dolutegravir (DTG) or TAF. Participants will be admitted to the Metabolic Unit of the NIH CC, undergo an initial baseline evaluation over 3 days, followed by an 8-day period during which they will take either drug (TAF or DTG) once daily. Following an 18-day washout period at home, participants will then be readmitted to the Metabolic Unit and assigned to the other drug, which they will follow for another 8 days. Throughout the study, participants will be assessed for metabolic processes, including 24-hour energy expenditure via metabolic chamber.

Primary Objective:

To determine if TAF or DTG induce changes in 24-hour energy expenditure and 24-hour respiratory quotient (RQ).

Secondary Objectives:

1. To determine if baseline demographic (eg, age, sex, or weight) or laboratory characteristics (eg, free thyroxine [T4], thyroid-stimulating hormone [TSH], cortisol, or other hormones) are associated with changes in 24-hour energy expenditure.

2. To determine if there is a correlation between steady-state pharmacokinetics of TAF or DTG and changes in 24-hour energy expenditure or caloric intake.

Exploratory Objective:

Evaluation of microbiota in vaginal, oral, and rectal mucosa, including potential reactivation of human endogenous retroviruses (HERVs) at start and the end of each treatment period (TAF and DTG).

Primary Endpoint:

Change in 24-hour energy expenditure and 24-hour RQ from baseline to day 1 and day 8 of ARV therapy with each drug.

Secondary Endpoints:

1. Relationship between demographic data or baseline laboratory values and changes in energy expenditure or caloric intake.

2. Relationship between pharmacokinetic parameters for TAF and DTG and changes in energy expenditure or caloric intake.

Exploratory Endpoint:

Potential changes in microbiome composition and HERVs reactivation after treatment periods with TAF or DTG. ;

Related Conditions & MeSH terms

• Healthy Volunteer
• Weight Gain

• NCT number: NCT05652478
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Mary McLaughlin, R.N.
• Phone: (301) 435-8001
• Email: mm149t@nih.gov
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 26, 2024
• Completion date: January 31, 2030