Insulin ResistancePhase 1TAF-IRNCT03092206
Changes in Insulin Sensitivity in Healthy Volunteers Taking Tenofovir Alafenamide (TAF)-Containing Antiretroviral Medication
A Phase 1 study testing F/TAF, E/C/F/TAF and R/F/TAF in people with Insulin Resistance, run by Technical University of Munich at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- F/TAF, E/C/F/TAF and R/F/TAF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 18 Apr 2017to 28 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male, healthy volunteers, age range ≥18-40 years
- Written informed consent and willingness to attend study visits
- Willingness for taking study medication during study period
- Birth control during study period
Who cannot join
- Participation in other interventional clinical trials and/or participation in another clinical trial with medicinal products within the last 4 weeks
- Known allergies or contraindications against study medication
- Known metabolic dysfunction, e.g. Hypertriglyceridemia or Diabetes mellitus
- Smoking or alcohol abuse (> 15g/day alcohol consumption)
- Documented HIV-infection
- BMI <18 >25
Show all 12Show fewer
- Recurrent medication or any antiretroviral medication within the last 30 days
- ALT, AST, Bilirubin, Creatinine, TSH, blood pressure, heart rate, QTc are out of normal range
- o Normal ranges for clinical chemistry are defined by local laboratory. For blood pressure normal range is defined as 100/60-140/90; for heart rate 60-100
- Known liver, kidney, heart, pulmonary, gastrointestinal, endocrinological, rheumathoid, neurological, psychiatric or metabolic diseases
- Any situation of which the sponsors sees relevant contraindication against study participation
- Imprisoned or situated people
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Changes in Insulin Sensitivity in Healthy Volunteers Taking Tenofovir Alafenamide (TAF)-Containing Antiretroviral Medication: The TAF-IR Study
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
Read the 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.
- Conditions
- Insulin Resistance
- Being tested
- F/TAF, E/C/F/TAF, R/F/TAF
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F/TAFDrug
Also called Descovy
antiretroviral therapy
E/C/F/TAFDrug
Also called Genvoya
antiretroviral therapy
R/F/TAFDrug
Also called Odefsey
antiretroviral therapy
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | F/TAF ; oral; Dose: 25/200 mg; Frequency: QD Receives: Drug: F/TAF |
| Group 2 | Experimental | Group 2: E/C/F/TAF; oral; Dose: 150/150/200/10 mg; Frequency: QD Receives: Drug: E/C/F/TAF |
| Group 3 | Experimental | Group 3: R/F/TAF; oral; Dose: 25/200/25 mg; Frequency: QD Receives: Drug: R/F/TAF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in insulin sensitivity
To assess changes in insulin sensitivity (mean glucose disposal rate normalized to body weight (MBW [mg glucose/min*kg]) in HIV-negative, healthy, non-obese (BMI 18-25) male volunteers following 14±2 days of treatment with group 1 or group 2 or group 3, as measured by HEGC.
Measured: 14±2 days
Secondary outcomes (2)
changes in insulin sensitivity
To asses changes in insulin sensitivity as measured by mean glucose disposal rate normalized to body weight and steady-state insulin concentration (MBW/L [mg glucose/min kg UIU]) and normalized to body weight and steady-state glucose concentration (MCR [dL/min kg]), HOMA-IR, HOMA-, QUICKI and 1/QUICKI indices in HIV-negative, healthy, non-obese male volunteers following 14 +/-2 days of administration of IMP in group 1, 2 or 3.
Measured: 14 +/-2 days
lipid metabolism
Changes in lipid metabolism in HIV-negative, healthy, non-obese male volunteers following 14±2 days of administration of IMP in group 1, 2 or 3.
Measured: 14±2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start18 Apr 2017
- Primary completion28 Jul 2017
- Study completion28 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group 1: F/TAF ; oral; Dose: 25/200 mg; Frequency: QD Group 2: E/C/F/TAF; oral; Dose: 150/150/200/10 mg; Frequency: QD Group 3: R/F/TAF; oral; Dose: 25/200/25 mg; Frequency: QD
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092206
- Sponsor's protocol ID
- TAF-1688-0030-I
- Acronym
- TAF-IR
- Status last verified
- Aug 2017
- First submitted
- 21 Mar 2017
- Last updated
- 21 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Insulin Sensitivity in Healthy Volunteers Taking Tenofovir Alafenamide (TAF)-Containing Antiretroviral Medication: The TAF-IR Study
- ClinicalTrials.gov ID
- NCT03092206
- Acronym / sponsor ID
- TAF-IR / TAF-1688-0030-I
- Conditions
- Insulin Resistance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 28 Jul 2017 (actual)
- Study completion
- 28 Jul 2017 (actual)
- First posted
- 27 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Group 1: F/TAF ; oral; Dose: 25/200 mg; Frequency: QD Group 2: E/C/F/TAF; oral; Dose: 150/150/200/10 mg; Frequency: QD Group 3: R/F/TAF; oral; Dose: 25/200/25 mg; Frequency: QD
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: F/TAFF/TAF ; oral; Dose: 25/200 mg; Frequency: QD |
| Group 2 | Experimental | Drug: E/C/F/TAFGroup 2: E/C/F/TAF; oral; Dose: 150/150/200/10 mg; Frequency: QD |
| Group 3 | Experimental | Drug: R/F/TAFGroup 3: R/F/TAF; oral; Dose: 25/200/25 mg; Frequency: QD |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male, healthy volunteers, age range ≥18-40 years
- Written informed consent and willingness to attend study visits
- Willingness for taking study medication during study period
- Birth control during study period
Key exclusion criteria (12 listed)
- Participation in other interventional clinical trials and/or participation in another clinical trial with medicinal products within the last 4 weeks
- Known allergies or contraindications against study medication
- Known metabolic dysfunction, e.g. Hypertriglyceridemia or Diabetes mellitus
- Smoking or alcohol abuse (> 15g/day alcohol consumption)
- Documented HIV-infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| F/TAFAlso: Descovyantiretroviral therapy | Drug | Group 1 |
| E/C/F/TAFAlso: Genvoyaantiretroviral therapy | Drug | Group 2 |
| R/F/TAFAlso: Odefseyantiretroviral therapy | Drug | Group 3 |
Primary outcome
Changes in insulin sensitivity
Time frame: 14±2 days
To assess changes in insulin sensitivity (mean glucose disposal rate normalized to body weight (MBW [mg glucose/min*kg]) in HIV-negative, healthy, non-obese (BMI 18-25) male volunteers following 14±2 days of treatment with group 1 or group 2 or group 3, as measured by HEGC.
2 secondary outcomes
changes in insulin sensitivity
Time frame: 14 +/-2 days
lipid metabolism
Time frame: 14±2 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing F/TAF, E/C/F/TAF and R/F/TAF in people with Insulin Resistance, run by Technical University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in insulin sensitivity (time frame: 14±2 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2017.