Trials / Recruiting
RecruitingNCT05652478
Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study
Early Metabolic Effects of Antiretroviral Drugs in Healthy Volunteers: A Phase 2 Randomized Study
- Status
- Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 120 (estimated)
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID) · NIH
- Sex
- All
- Age
- 18 Years – 55 Years
- Healthy volunteers
- Accepted
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 characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection Eligibility: Healthy people aged 18 to 55. Design: Participants will be screened in the outpatient clinic. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function. Participants will be randomized to one of four oral treatments: Tenofovir Disoproxil Fumarate TDF/Viread, Tenovovir Alafenamide TAF/Vemlidy, Dolutegravir DTG/Tivicay, or both TAF and DTG taken together for 4 weeks. Participants will have a Day 0 visit for the Lead-In Baseline visit for an exam and blood tests and continuous glucose monitor placement. Participants will return in 2wks or Day 14/Wk 2 for a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density. Optional adiopse (fat) tissue biopsy in the abdomen, and optional microbiome specimen collections. Continuous glucose monitor changed. Oral once a day dose medication will be started with education. Participants will return in 2wks or Day 28/Wk 4 for exam, labs, and continuous glucose monitor changed. Participants will return in 2wks or Day 42/Wk 6 for final exam, labs, repeat DEXA scan, repeat adipose tissue biopsy, and microbiome specimen collections.
Detailed description
Study Description: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral (ARV) drugs that are currently among first-line therapies to treat and prevent HIV. 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 incompletely understood. In addition, one of these marketed drugs (bictegravir) is coformulated in combination with the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir alafenamide (TAF), which may also independently contribute to weight gain, including when it is compared against the related prodrug tenofovir disoproxil fumarate (TDF). To better understand the effects of INSTIs and TAF on metabolism, healthy volunteer participants will be randomized 1:1:1:1 to one of four arms: the INSTI dolutegravir (DTG), TAF, DTG plus TAF, or TDF. Participants will undergo an initial screening evaluation, a 2-week treatment-free lead-in period, and then a 4-week open-label treatment phase during which they will take the assigned study drug(s). During the study, participants will be assessed for changes in metabolic pathways, metabolites, and gene expression using a multi-omic approach. They will undergo serial research sample collection, including adipose tissue biopsy and microbiome sampling, both prior to initiation and after 4 weeks of the study drug(s). Objectives: Primary Objective: To characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection. Secondary Objectives: * To characterize the change in plasma proteomics and lipidomics that 4 weeks of each treatment may induce in the absence of HIV infection. * To characterize the change in peripheral blood mononuclear cell (PBMC) transcriptomics and cell populations that 4 weeks of each treatment may induce in the absence of HIV infection. * To characterize the changes in adipose tissue via RNA sequencing, metabolomics, and proteomics that 4 weeks of each treatment may induce in the absence of HIV infection. * To determine if baseline (prior to study agent administration) demographics (eg, age, sex, or weight) or laboratory characteristics (eg, free thyroxine \[T4\], thyroid-stimulating hormone \[TSH\], cortisol, or other hormones) are associated with multi-omic changes induced by each treatment. * To compare the multi-omic changes induced by DTG and/or TAF versus TDF in the absence of HIV infection. Exploratory Objectives: * To determine if there is a correlation between pharmacokinetic (PK) measurements of TAF, DTG, or TDF and multi-omic changes. * 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. Endpoints: Primary Endpoint: Change in plasma metabolites from ARV initiation to the end of the 4-week period of ARV therapy with each treatment. Secondary Endpoints: * Comprehensive multi-omic profile changes in plasma, PBMCs, and adipose tissue from ARV initiation to the end of the 4-week treatment period with each treatment, encompassing transcriptomic changes, metabolomic alterations, lipidomic shifts, and proteomic variations. * Relationship between demographic data or baseline laboratory values and multi-omic profile changes in plasma, PBMC, and adipose tissue. * Multi-omic comparisons between DTG and/or TAF versus TDF. Exploratory Endpoints: * Relationship between PK parameters for TAF, DTG, and TDF and multi-omic profile changes in plasma, PBMC, and adipose tissue. * Potential changes in microbiome composition and HERV reactivation after treatment periods.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Dolutegravir (DTG) AND Tenofovir alafenamide (TAF) | 50mg dolutegravir (DTG) one tablet AND 25mg tenofovir alafenamide (TAF) one tablet together, orally once daily for 4 wks (Day 14 to Day 42) |
| DRUG | Tenofovir Disoproxil Fumarate | 300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42) |
| DRUG | Dolutegravir | 50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42) |
| DRUG | Tenofovir alafenamide | 25mg tenofovir alafenamide (TAF) one tablet orally once a day for 4 wks (Day 14 to Day 42) |
Timeline
- Start date
- 2026-04-22
- Primary completion
- 2028-01-31
- Completion
- 2030-01-31
- First posted
- 2022-12-15
- Last updated
- 2026-04-17
Locations
1 site across 1 country: United States
Source: ClinicalTrials.gov record NCT05652478. Inclusion in this directory is not an endorsement.