Effects of Etravirine on Endothelial Function in HIV-uninfected Adults: A Pilot Study

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effects of etravirine, an HIV antiretroviral medication, on vascular function.

Detailed Description
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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.

Official Title
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Effects of Etravirine (INTELENCETM) on Endothelial Function in HIV-uninfected Adults: A Pilot Study

Conditions
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Endothelial Function, Lipids, Insulin Resistance, Inflammation, HIV Infections

Intervention / Treatment
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* Drug: Etravirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Negative ELISA for HIV-1 or HIV-2 at screening Negative hepatitis B surface antigen at screening Negative hepatitis C antibody at screening 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 No history of diabetes, hypertension, or dyslipidemia No anticipated changes or additions to other medical therapies during the course of the study Exclusion Criteria: Inability to provide written, informed consent Known allergy/intolerance to etravirine or nitroglycerin Absolute neutrophil count < 750cell/mL at screening Hemoglobin <11g/dL at screening Platelet count <100,000/mL at screening Estimated creatinine clearance (per Cockcroft-Gault equation) <55 mL/min at screening Liver transaminases (AST or ALT) > 100 IU/mL or total bilirubin > 1.5mg/dL at screening Breastfeeding at screening and during the course of the study Hypotension, defined as SBP<90mmHg at time of each main study visit before brachial artery ultrasound measurements 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 Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis), within 72 hours (before or after) of brachial artery reactivity testing Indwelling vascular catheters within any upper body vessel at time of brachial artery reactivity testing Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements 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 History of migraine headaches History of Raynaud's phenomenon History of cardiac arrythmias History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH outside the normal range on most recent testing during normal clinical care) History of carotid bruits. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or nicotine replacement treatments (patch, gum) within one year of screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Etravirine|Two one-hundred mg tablets orally twice daily for four weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Entry and four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Endothelial function, Etravirine