Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study

NCT05652478 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000906000906-I
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Weight Gain; Healthy Volunteer; Metabolic Effects; Integrase Strand Transfer Inhibitors

Keywords

Metabolism; HIV; Integrase Strand Transfer Inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in plasma metabolites from ARV initiation to the end of the 4 week period of ARV therapy with each treatment

  To determine if TAF or DTG or TDF or DTG/TAF induce changes in plasma metabolites in the 4wks of therapy

  Day 14/Wk2 to Day 42/Wk6 of ARV therapy for each of 4 drug regimen.

Secondary Outcomes (4)

• Encompassing transcriptomic changes, metabolic alterations, lipidomic shifts, and proteomic variations.

  Throughout study - Baseline to Day 42/Wk 6

• 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 of four treatments

  Throughout study - Baseline to Day 42/Wk 6

• Relationship between demographic data or baseline laboratory values and multi-omic profile changes in plasma, PBMC, and adipose tissue.

  Throughout study - Baseline to Day 42/Wk 6

• Multi-omic comparisons between DTG and/or TAF versus TDF.

  Throughout study - Baseline to Day 42/Wk 6

Study Arms (4)

Dolutegravir

ACTIVE COMPARATOR

50mg one tablet orally once a day for 4 weeks, Day 14 to Day 42

Drug: Dolutegravir

Dolutegravir AND Tenofovir alafenamide

ACTIVE COMPARATOR

50mg one tablet orally AND 25mg one tablet orally together once a day for 4 weeks, Day 14 to Day 42

Drug: Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)

Tenofovir alafenamide

ACTIVE COMPARATOR

25mg one tablet orally once a day for 4 weeks, Day 14 to Day 42

Drug: Tenofovir alafenamide

Tenofovir Disoproxil Fumarate

ACTIVE COMPARATOR

300mg one tablet orally once daily for 4 weeks, Day 14 to Day 42

Drug: Tenofovir Disoproxil Fumarate

Interventions

Tenofovir Disoproxil Fumarate DRUG

300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42)

Tenofovir Disoproxil Fumarate

Dolutegravir (DTG) AND Tenofovir alafenamide (TAF) DRUG

50mg dolutegravir (DTG) one tablet AND 25mg tenofovir alafenamide (TAF) one tablet together, orally once daily for 4 wks (Day 14 to Day 42)

Dolutegravir AND Tenofovir alafenamide

Dolutegravir DRUG

50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42)

Dolutegravir

Tenofovir alafenamide DRUG

25mg tenofovir alafenamide (TAF) one tablet orally once a day for 4 wks (Day 14 to Day 42)

Tenofovir alafenamide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged 18 to 55 years.
• Able to provide informed consent.
• Willing to allow samples and data to be stored and shared for future research.
• Agrees to use a barrier method of contraception or abstain from sexual activity starting at screening though the end of study participation.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Current infection with HIV or hepatitis A, B, or C.
• Body mass index (BMI) \<18.5 kg/m\^2 or \>30.0 kg/m\^2.
• Weight change \>5% in the past 6 months.
• History of or current cardiovascular disease such as congestive heart failure, heart block, or clinically relevant abnormal ECG as determined by investigators.
• History of or current liver disease or alanine transaminase serum level \>2x upper limit of normal.
• History of or current kidney disease or renal insufficiency, or estimated creatinine clearance \<=80 mL/min (Modification of Diet in Renal Disease equation).
• Current cancer or history of cancer within 5 years of screening, with the exception of squamous cell carcinoma or basal cell carcinoma that is localized and does not require systemic therapy.
• History of bariatric surgery.
• Diabetes mellitus as defined by a prior diagnosis or a hemoglobin A1c of \>6.4 percent on screening labs.
• Fasting serum glucose \>126 mg/dL.
• History of or current hypo- or hyper-thyroid or abnormal TSH, except minor deviations deemed to be of no clinical significance by the investigator.
• History of or current asthma or chronic obstructive pulmonary disease.
• Psychological conditions by self-report, such as (but not limited to) clinical depression, bipolar disorders, which would be incompatible with safe and successful participation in this study.
• Pregnancy or within 1 year post-partum.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016 Sep;3(9):e410-e420. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.

  PMID: 27562742 BACKGROUND

• Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, Kulagin V, Givens N, de Oliveira CF, Brennan C; FLAMINGO study team. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015 Apr;2(4):e127-36. doi: 10.1016/S2352-3018(15)00027-2. Epub 2015 Mar 10.

  PMID: 26424673 BACKGROUND

• Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, Kuritzkes DR, Sagar M, Brown TT, Cohn SE, McComsey GA, Aweeka F, Fichtenbaum CJ, Presti RM, Koletar SL, Haas DW, Patterson KB, Benson CA, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS; ACTG A5257 Team. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461-71. doi: 10.7326/M14-1084.

  PMID: 25285539 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Weight Gain

Interventions

dolutegravir; tenofovir alafenamide; Tenofovir

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brian P Epling, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary E McLaughlin, R.N.

CONTACT

(301) 435-8001; mmclaughli@niaid.nih.gov

Brian P Epling, M.D.

CONTACT

(240) 460-9309; brian.epling@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2022
• First Posted: December 15, 2022
• Study Start (Estimated): June 17, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2030
• Last Updated: June 12, 2026

Record last verified: 2026-04-15

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)