Early Metabolic Effects of Dolutegravir or Tenofovir Alefenamide in Healthy Volunteers

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Dec 14, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at how a medication called dolutegravir (DTG), used to treat HIV, affects the way the body uses energy, especially in terms of weight gain. Researchers want to compare its effects with another medication called tenofovir alafenamide (TAF), which is not an integrase strand transfer inhibitor (INSTI). Understanding these effects is important because weight gain from these medications can lead to health problems like diabetes and heart disease.

To participate in the study, you must be a healthy adult aged 18 to 55 who can stay in a clinical setting for two separate 11-night stays. You should not have any major health issues, including HIV or liver disease, and your body weight should fall within a certain range. During the study, you’ll take either DTG or TAF for eight days and undergo several tests to see how your body processes energy. This includes spending time in a special room that measures your breathing and having scans to assess your body fat and muscle mass. This study is currently recruiting participants, and your health will be closely monitored throughout the trial.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• 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 and able to stay in the whole-room indirect calorimetry suite on 6 occasions.
• • Willing to reside on the metabolic unit in the Clinical Center for 2 stays of 11 consecutive days over the course of 5 weeks.
• • Willing to allow samples and data to be stored and shared for future research.
• EXCLUSION CRITERIA:
• 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 or a trained athlete.
• • 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 \<=50 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.
• • 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.
• • History of or current glaucoma.
• • Psychological conditions by self-report, such as (but not limited to) claustrophobia, clinical depression, bipolar disorders, that would be incompatible with safe and successful participation in this study.
• • Pregnancy or within 1 year post-partum.
• • Experiences irregular menstrual cycles.
• • Breastfeeding.
• • Blood pressure \>140/90 mm Hg or current antihypertensive therapy.
• • Anemia, defined as hemoglobin \<13 g/dL (males) or \<12 g/dL (females).
• • History of illicit drug, opioids, or alcohol abuse within the last 5 years; current use of illicit drugs or opioids (by history) or excessive alcohol (CAGE assessment score \>=2).
• • Current use of medications/dietary supplements/alternative therapies known to alter energy metabolism.
• • Current use of prescription medications, including recent use (6 months) of Descovy or Truvada (eg, for purposes of PrEP).
• • Any history of exposure to cabotegravir (eg, as participant in research study for this drug).
• • Current use of nonprescriptive medications that may have interactions with study drugs as determined by the investigators.
• • History of adverse or allergic reactions to the study drugs.
• • Daily caffeine intake \>500 mg (about 4 cups of coffee)
• • Current smoker or user of tobacco products.
• • Participants with dietary allergies, intolerances, or eating patterns that would preclude them from consuming controlled metabolic meals.
• • Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Trial Officials