Ignite Creation Date:
2025-12-26 @ 5:24 PM
Ignite Modification Date:
2026-01-10 @ 1:31 AM
Study NCT ID:
NCT03092206
Status:
COMPLETED
Last Update Posted:
2017-08-21
First Post:
2017-03-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Changes in Insulin Sensitivity in Healthy Volunteers Taking Tenofovir Alafenamide (TAF)-Containing Antiretroviral Medication
Sponsor:
Technical University of Munich
Organization:
Study Overview
Official Title:
Changes in Insulin Sensitivity in Healthy Volunteers Taking Tenofovir Alafenamide (TAF)-Containing Antiretroviral Medication: The TAF-IR Study
Status:
COMPLETED
Status Verified Date:
2017-08
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:
TAF-IR
Brief Summary:
Investigation of possible changes in insulin sensitivity in healthy volunteers taking the following HIV treatment combinations: F/TAF (group 1) as compared to E/C/F/TAF (group 2) as compared to R/F/TAF (group 3). The measurement of insulin sensitivity will be performed in 30 HIV-negative healthy non-obese (BMI 18-25) male volunteers before and after 14±2 days of treatment. The volunteers will be randomly assigned to one of the three groups. Changes in insulin sensitivity will be measured by golden standard hyperinsulinemic euglycemic clamp (HEGC) technique, using glucose and insulin infusion as diagnostic agents
Detailed Description:
Nearly immediately following the characterization of HIV, the metabolic disturbances in HIV-positive patients, particularly changes in insulin sensitivity, were reported. The chronic inflammation due to metabolic changes caused by HIV-Infection on one hand and the antiretroviral therapy (ART) itself on the other hand were considered major contributors to pathological changes in insulin sensitivity in HIV-positive patients. There were two possible mechanisms discussed in the literature: Direct effects on insulin-associated cellular glucose uptake and indirect effects of changes in lipid metabolism, i.e. the lipotoxicity. Particularly, thymidine analogues, such as nucleoside reverse transcriptase inhibitors (NRTI) were strongly linked to lipotoxicity and depletion of mitochondric DNA, causing insulin resistance (IR) in HIV-positive patients and healthy volunteers, ultimately resulting in overt diabetes mellitus. Furthermore, protease inhibitors (PI) showed lipotoxicity, further increasing insulin resistance.
The incidence of insulin resistance and, ultimately, diabetes mellitus in patients receiving ART increases over time, significantly contributing to cardiovascular morbidity and mortality in HIV-positive patients. Due to significant increases both in life expectation and duration of ART in HIV-patients, the early recognition of unfavorable metabolic changes (i. e. insulin resistance) gains in importance. Particularly, the considerations of long-term toxicity and safety of ART are receiving more and more attention. Unfortunately, the appropriate strategies for screening, surveillance and therapeutic consequences are not well established in HIV-positive patients.
While the very well established HIV nucleoside reverse transcriptase inhibitor Tenofovir disaproxil fumarate (TDF) was associated with a favorable influence on lipids and with no known negative effects on insulin sensitivity, the new drug Tenofovir alafenamide (TAF) has not been analyzed in concern of changes in insulin sensitivity yet. As TAF has been recently submitted for approval by FDA and EMEA for treatment of HIV-positive patients, widespread use and potential replacement of TDF can be expected soon. Fixed dose combinations with Emtricitabine (F/TAF) or cobicistat-boosted elvitegravir (E/C/F/TAF) or rilpivirine (R/F/TAF) have been developed and will take part in ART settings. Unfortunately, only limited data exists on metabolic effects of TAF or TAF-containing fixed dose combination drugs, particularly concerning changes in lipid metabolism and insulin sensitivity in HIV-positive patients or healthy volunteers. For providing more safety data concerning changes in insulin sensitivity and associated effects on lipids more data should be provided.
We intend to investigate the possible changes in insulin sensitivity, measured as described below by "hyperinsulinemic eugylcemic clamp" in healthy volunteers taking TAF/FTC (group 1) as compared to E/C/F/TAF (group 2) as compared to R/F/TAF (group 3). To our best of knowledge, there are currently no data available investigating changes in insulin sensitivity of TAF-containing ART-regiments.
The incidence of insulin resistance and, ultimately, diabetes mellitus in patients receiving ART increases over time, significantly contributing to cardiovascular morbidity and mortality in HIV-positive patients. Due to significant increases both in life expectation and duration of ART in HIV-patients, the early recognition of unfavorable metabolic changes (i. e. insulin resistance) gains in importance. Particularly, the considerations of long-term toxicity and safety of ART are receiving more and more attention. Unfortunately, the appropriate strategies for screening, surveillance and therapeutic consequences are not well established in HIV-positive patients.
While the very well established HIV nucleoside reverse transcriptase inhibitor Tenofovir disaproxil fumarate (TDF) was associated with a favorable influence on lipids and with no known negative effects on insulin sensitivity, the new drug Tenofovir alafenamide (TAF) has not been analyzed in concern of changes in insulin sensitivity yet. As TAF has been recently submitted for approval by FDA and EMEA for treatment of HIV-positive patients, widespread use and potential replacement of TDF can be expected soon. Fixed dose combinations with Emtricitabine (F/TAF) or cobicistat-boosted elvitegravir (E/C/F/TAF) or rilpivirine (R/F/TAF) have been developed and will take part in ART settings. Unfortunately, only limited data exists on metabolic effects of TAF or TAF-containing fixed dose combination drugs, particularly concerning changes in lipid metabolism and insulin sensitivity in HIV-positive patients or healthy volunteers. For providing more safety data concerning changes in insulin sensitivity and associated effects on lipids more data should be provided.
We intend to investigate the possible changes in insulin sensitivity, measured as described below by "hyperinsulinemic eugylcemic clamp" in healthy volunteers taking TAF/FTC (group 1) as compared to E/C/F/TAF (group 2) as compared to R/F/TAF (group 3). To our best of knowledge, there are currently no data available investigating changes in insulin sensitivity of TAF-containing ART-regiments.
Study Oversight
Has Oversight DMC:
False
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?:
False
Is an FDA AA801 Violation?: