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

NCT05652478 | Recruiting Phase 2

• 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 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.

Conditions

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

Keywords

Metabolism; HIV; Integrase Strand Transfer Inhibitors

Outcome Measures

Primary Outcomes (1)

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

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

  Baseline to day 1 and Day 8 of ARV therapy for drug regimen.

Secondary Outcomes (2)

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

  Throughout study

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

  Days 10 and 38

Study Arms (2)

Dolutegravir

ACTIVE COMPARATOR

50mg one tablet orally once daily for 8 days.

Drug: Dolutegravir

Tenofovir alafenamide

ACTIVE COMPARATOR

25mg one tablet orally once a day for 8 days.

Drug: Tenofovir alafenamide

Interventions

Tenofovir alafenamide DRUG

25mg tenofovir alafenamide (TAF) one tablet orally once a day for 8 days.

Tenofovir alafenamide

Dolutegravir DRUG

50mg dolutegravir (DTG) one tablet orally once daily for 8 days.

Dolutegravir

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

tenofovir alafenamide; dolutegravir

Condition Hierarchy (Ancestors)

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

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: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2022
• First Posted: December 15, 2022
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2030
• Last Updated: April 16, 2026

Record last verified: 2025-08-13

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)