Endothelial Function, HIV Infections, Inflammation, Insulin Resistance, Lipids
Conditions
Keywords
HIV, Endothelial function, Etravirine
Brief summary
The purpose of this study is to determine the safety and effects of etravirine, an HIV antiretroviral medication, on vascular function.
Detailed description
We hypothesize that in HIV-uninfected subjects, etravirine 200mg twice daily for four weeks will have no effect on endothelial function. The primary objective of this study is to determine the effects of etravirine 200mg twice daily given for four weeks on endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, in HIV-uninfected subjects. Secondary objectives include determination of the effects of etravirine 200mg twice daily given for four weeks on safety measures, lipid fractions, HOMA-IR, blood pressure, inflammatory parameters, and endothelial activation parameters.
Interventions
DRUGEtravirine
Two one-hundred mg tablets orally twice daily for four weeks
Sponsors
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Indiana University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. 18 years of age or older 2. Negative ELISA for HIV-1 or HIV-2 at screening 3. Negative hepatitis B surface antigen at screening 4. Negative hepatitis C antibody at screening 5. For women of reproductive potential, a negative urine pregnancy test at screening and willingness to use two forms of birth control during the course of the study 6. No history of diabetes, hypertension, or dyslipidemia 7. No anticipated changes or additions to other medical therapies during the course of the study
Exclusion criteria
1. Inability to provide written, informed consent 2. Known allergy/intolerance to etravirine or nitroglycerin 3. Absolute neutrophil count \< 750cell/mL at screening 4. Hemoglobin \<11g/dL at screening 5. Platelet count \<100,000/mL at screening 6. Estimated creatinine clearance (per Cockcroft-Gault equation) \<55 mL/min at screening 7. Liver transaminases (AST or ALT) \> 100 IU/mL or total bilirubin \> 1.5mg/dL at screening 8. Breastfeeding at screening and during the course of the study 9. Hypotension, defined as SBP\<90mmHg at time of each main study visit before brachial artery ultrasound measurements 10. Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids (\>10mg/day of prednisone or the equivalent), or anabolic steroids within 30 days of each screening visit or each main study visit 11. Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis), within 72 hours (before or after) of brachial artery reactivity testing 12. Indwelling vascular catheters within any upper body vessel at time of brachial artery reactivity testing 13. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements 14. Acute therapy for serious infection or other serious medical illnesses (in the judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to each screening and study visit 15. History of migraine headaches 16. History of Raynaud's phenomenon 17. History of cardiac arrythmias 18. History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH outside the normal range on most recent testing during normal clinical care) 19. History of carotid bruits. 20. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or nicotine replacement treatments (patch, gum) within one year of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated Dilation (FMD) of the Brachial Artery | Entry and four weeks | FMD is measured as the percentage increase in brachial artery diameter after increase in blood flow. We measured the change in this percentage from entry (before etravirine was started) and again at four weeks after receiving etravirine. |
Secondary
| Measure | Time frame |
|---|---|
| Lipid Fractions | Four weeks |
| Insulin Sensitivity [(Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)] | Four weeks |
| Blood Pressure | Four weeks |
| Inflammatory Biomarkers | Four weeks |
| Endothelial Activation Biomarkers | Four weeks |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between April 2009 and March 2010. Participants were recruited via advertisements and word-of-mouth.
Pre-assignment details
After participant enrollment, a screening visit was performed to determine eligibility. Participants may have been excluded from entering the study if they were found to be ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Etravirine Healthy volunteers receiving etravirine 200mg orally twice daily | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Etravirine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age Continuous | 40 years |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Flow-mediated Dilation (FMD) of the Brachial Artery
FMD is measured as the percentage increase in brachial artery diameter after increase in blood flow. We measured the change in this percentage from entry (before etravirine was started) and again at four weeks after receiving etravirine.
Time frame: Entry and four weeks
Population: FMD analysis was per protocol restricted to those who completed the four week trial. The safety analysis was ITT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etravirine | Flow-mediated Dilation (FMD) of the Brachial Artery | 0.03 Percentage |
p-value: 0.36Wilcoxon signed-rank
Secondary
Blood Pressure
Time frame: Four weeks
Secondary
Endothelial Activation Biomarkers
Time frame: Four weeks
Secondary
Inflammatory Biomarkers
Time frame: Four weeks
Secondary
Insulin Sensitivity [(Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)]
Time frame: Four weeks
Secondary
Lipid Fractions
Time frame: Four weeks