Ignite Creation Date:
2024-05-06 @ 6:24 PM
Last Modification Date:
2024-10-26 @ 2:47 PM
Study NCT ID:
NCT05652478
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2022-12-10
Brief Title:
Early Metabolic Effects of Dolutegravir or Tenofovir Alefenamide in Healthy Volunteers
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase 2 Randomized Cross-Over Design Study of the Early Metabolic Effects of Dolutegravir or Tenofovir Alafenamide in Healthy Volunteers
Status:
RECRUITING
Status Verified Date:
2024-09-19
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Study Description
Integrase strand transfer inhibitors INSTIs are a class of antiretroviral ARV drugs currently included in first-line therapy to treat HIV infection 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 unknown In addition these marketed drugs are formulated in combination with the nucleotide reverse transcriptase inhibitor NRTI tenofovir alafenamide TAF which may also independently contribute to weight gain as compared to the older formulation of tenofovir disoproxil fumarate TDF To better understand the effects of INSTIs and TAF on metabolism participants will be randomized 11 to either the INSTI dolutegravir DTG or TAF Participants will be admitted to the Metabolic Unit of the NIH CC undergo an initial baseline evaluation over 3 days followed by an 8-day period during which they will take either drug TAF or DTG once daily Following an 18-day washout period at home participants will then be readmitted to the Metabolic Unit and assigned to the other drug which they will follow for another 8 days Throughout the study participants will be assessed for metabolic processes including 24-hour energy expenditure via metabolic chamber
Primary Objective
To determine if TAF or DTG induce changes in 24-hour energy expenditure and 24-hour respiratory quotient RQ
Secondary Objectives
1 To determine if baseline demographic eg age sex or weight or laboratory characteristics eg free thyroxine T4 thyroid-stimulating hormone TSH cortisol or other hormones are associated with changes in 24-hour energy expenditure
2 To determine if there is a correlation between steady-state pharmacokinetics of TAF or DTG and changes in 24-hour energy expenditure or caloric intake
Exploratory Objective
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 period TAF and DTG
Primary Endpoint
Change in 24-hour energy expenditure and 24-hour RQ from baseline to day 1 and day 8 of ARV therapy with each drug
Secondary Endpoints
1 Relationship between demographic data or baseline laboratory values and changes in energy expenditure or caloric intake
2 Relationship between pharmacokinetic parameters for TAF and DTG and changes in energy expenditure or caloric intake
Exploratory Endpoint
Potential changes in microbiome composition and HERVs reactivation after treatment periods with TAF or DTG
Integrase strand transfer inhibitors INSTIs are a class of antiretroviral ARV drugs currently included in first-line therapy to treat HIV infection 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 unknown In addition these marketed drugs are formulated in combination with the nucleotide reverse transcriptase inhibitor NRTI tenofovir alafenamide TAF which may also independently contribute to weight gain as compared to the older formulation of tenofovir disoproxil fumarate TDF To better understand the effects of INSTIs and TAF on metabolism participants will be randomized 11 to either the INSTI dolutegravir DTG or TAF Participants will be admitted to the Metabolic Unit of the NIH CC undergo an initial baseline evaluation over 3 days followed by an 8-day period during which they will take either drug TAF or DTG once daily Following an 18-day washout period at home participants will then be readmitted to the Metabolic Unit and assigned to the other drug which they will follow for another 8 days Throughout the study participants will be assessed for metabolic processes including 24-hour energy expenditure via metabolic chamber
Primary Objective
To determine if TAF or DTG induce changes in 24-hour energy expenditure and 24-hour respiratory quotient RQ
Secondary Objectives
1 To determine if baseline demographic eg age sex or weight or laboratory characteristics eg free thyroxine T4 thyroid-stimulating hormone TSH cortisol or other hormones are associated with changes in 24-hour energy expenditure
2 To determine if there is a correlation between steady-state pharmacokinetics of TAF or DTG and changes in 24-hour energy expenditure or caloric intake
Exploratory Objective
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 period TAF and DTG
Primary Endpoint
Change in 24-hour energy expenditure and 24-hour RQ from baseline to day 1 and day 8 of ARV therapy with each drug
Secondary Endpoints
1 Relationship between demographic data or baseline laboratory values and changes in energy expenditure or caloric intake
2 Relationship between pharmacokinetic parameters for TAF and DTG and changes in energy expenditure or caloric intake
Exploratory Endpoint
Potential changes in microbiome composition and HERVs reactivation after treatment periods with TAF or DTG
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 000906-I | None | None | None |