Dolutegravir + Tenofovir Alefenamide Metabolic Effects in Healthy Volunteers
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Must not be taking: Anticonvulsants, Rifamycins, St. John's wort, others
Disqualifiers: HIV, Hepatitis, Diabetes, Cardiovascular, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires participants to stop taking certain medications and supplements that can affect energy metabolism, such as carbamazepine, metformin, and thyroid medications, among others. If you are taking any of these, you would need to stop them to participate in the study.
What data supports the effectiveness of the drug Dolutegravir + Tenofovir Alefenamide?
The research suggests that switching to a dolutegravir-based regimen may have different metabolic effects compared to tenofovir alafenamide-based regimens, such as changes in cholesterol and body weight. However, specific effectiveness data for the combination of Dolutegravir and Tenofovir Alefenamide in healthy volunteers is not directly provided.
12345What makes the drug Dolutegravir + Tenofovir Alefenamide unique compared to other treatments?
Dolutegravir + Tenofovir Alefenamide is unique because it combines two drugs that work together to treat HIV by blocking the virus from multiplying, which is different from other treatments that might use different combinations or single drugs. This combination is known for its effectiveness and lower side effects compared to older HIV treatments.
678910Eligibility Criteria
Healthy individuals aged 18 to 55 who can consent and stay in a clinic for two periods of 11 days. They shouldn't have asthma, COPD, HIV, hepatitis A/B/C, extreme weight changes recently or be athletes. No cancer (except certain skin cancers), diabetes, thyroid issues, glaucoma, psychological conditions like claustrophobia or depression that affect participation safety. Not for pregnant/post-partum women or those with high blood pressure, anemia, drug/alcohol abuse history within five years.Inclusion Criteria
Able to provide informed consent
Willing to allow samples and data to be stored and shared for future research
I am willing to stay in the hospital for two 11-day periods over 5 weeks.
+2 more
Exclusion Criteria
Fasting serum glucose >126 mg/dL
Anemia, defined as hemoglobin <13 g/dL (males) or <12 g/dL (females)
I have had weight loss surgery in the past.
+26 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline Evaluation
Participants undergo an initial baseline evaluation over 3 days
3 days
Inpatient stay
Treatment Period 1
Participants take either DTG or TAF once daily for 8 days during the first inpatient stay
8 days
Inpatient stay
Washout Period
Participants have an 18-day washout period at home between treatment periods
18 days
Treatment Period 2
Participants take the alternate drug (DTG or TAF) once daily for 8 days during the second inpatient stay
8 days
Inpatient stay
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing how the HIV medication dolutegravir affects body energy use compared to tenofovir alafenamide. Participants will take one drug for eight days during each clinic stay and undergo tests including room calorimetry measuring oxygen intake and carbon dioxide output six times; DEXA scans for body fat and bone density; plus other assessments of body composition.
2Treatment groups
Active Control
Group I: Tenofovir alafenamideActive Control1 Intervention
25mg one tablet orally once a day for 8 days.
Group II: DolutegravirActive Control1 Intervention
50mg one tablet orally once daily for 8 days.
Dolutegravir is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:
🇪🇺 Approved in European Union as Tivicay for:
- HIV-1 infection
🇺🇸 Approved in United States as Tivicay for:
- HIV-1 infection
🇨🇦 Approved in Canada as Tivicay for:
- HIV-1 infection
🇯🇵 Approved in Japan as Tivicay for:
- HIV-1 infection
🇨🇭 Approved in Switzerland as Tivicay for:
- HIV-1 infection
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
References
Change in metabolic parameters after switching from triple regimens with tenofovir alafenamide to dolutegravir-based dual therapy. Bi-lipid study. [2023]The use of tenofovir alafenamide (TAF) has been associated with increased cholesterol and body weight. Real-life data on the metabolic effects of switching from a TAF-based triple regimen to a dolutegravir (DTG)-based two-drug regimen (2-DR) are scarce.
Switching from tenofovir alafenamide to tenofovir disoproxil fumarate improves lipid profile and protects from weight gain. [2022]Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) increases low-density lipoprotein cholesterol (LDL-C) and body weight. Metabolic effects of the opposite TAF-to-TDF switch are unknown.
Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens. [2023]Cardiometabolic outcomes were investigated 3 years after switching to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) vs continuing 3-/4-drug tenofovir alafenamide (TAF)-based regimens in a multicenter phase 3 noninferiority study based on an open-label randomized design.
Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV. [2021]Whilst reporting improved renal and bone safety profiles, studies have noted changes in lipid profiles among people living with HIV (PLWH) receiving antiretroviral therapy (ART) switching away from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We aimed to characterize changes in lipids observed after switching to TAF-containing ART in a real-world setting.
Weight gain following the single substitution of tenofovir disoproxil fumarate by tenofovir alafenamide in HIV-infected people from the French Dat'AIDS cohort: A propensity score-matched analysis. [2023]To minimize confounding factors, we aimed to describe the changes in weight and body mass index (BMI) following the single substitution of tenofovir disoproxil fumarate (TDF) by tenofovir alafenamide (TAF) in people living with HIV (PLWH).
Effect of dexfenfluramine on energy expenditure in obese patients on a very-low-calorie-diet. [2014]To investigate the effect of dexfenfluramine (dF) on Energy Expenditure (EE).
Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus. [2019]To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P
Correlation between metabolic and behavioral effects of dexfenfluramine treatment. [2013]The consequences of dexfenfluramine (dFF) treatments on food intake (FI), locomotor activity (LA), respiratory quotient (RQ), and on changes in metabolic rate (MR) and in RQ that are induced by LA and FI, were investigated in 12 female Wistar rats fed ad libitum. Reduction of FI induced by dFF was correlated with an overall decrease in RQ that expresses increased lipogenesis. For a given amount of activity, MR and RQ changes were enhanced by dFF. On the other hand, dFF appeared to increase energy expenditure in relation to FI only to the extent that the energetic cost of LA itself was not taken into account. It is concluded that the anorexia induced by dFF may be due to the peripheral consequences of dFF treatments on the peripheral metabolism of glucides and lipids according to a lipostatic, glucostatic, or an ischymetric mechanism, and that the increase in energy expenditure previously reported after feeding, may reflect an increase in the energy produced in relation to LA rather than an increase in the thermic effect of feeding per se.
Dexfenfluramine reduces cardiovascular risk factors. [2014]This study investigated the potential for dexfenfluramine to improve biochemical and clinical risk factors for cardiovascular disease, in obese dyslipidaemic individuals. Dexfenfluramine, the dextro isomer of fenfluramine, has been shown to aid weight reduction and lower blood lipids in normal subjects, and to improve glucose tolerance and insulin sensitivity in subjects with diabetes mellitus. Twenty-nine overweight (mean weight 83.3 +/- 11.3 kg), hyperlipidaemic (mean total cholesterol 7.3 +/- 1.2 mol/l) subjects participated in a 12-week randomized double-blind parallel study of dexfenfluramine versus placebo. After an eight-week dietary run-in phase, subjects were randomised to treatment with either dexfenfluramine or placebo for 12 weeks. During the run-in, energy intakes fell in both groups (5.5% for dexfenfluramine, 5% for placebo, no significant difference between groups). Dietary composition improved, fat as a percentage of energy decreased (14%, P
Dexfenfluramine in type II diabetes: effect on weight and diabetes control. [2022]To assess the effect of dexfenfluramine on weight loss, diabetic control and blood lipids in type II diabetics over a three-month period.