Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress

Study Overview
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Brief Summary
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The purpose of this study is to compare the cardiovascular profiles of efavirenz and rilpivirine, which are two drugs used to treat HIV infection.

Detailed Description
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This is a randomized, controlled, open-label, single-center study comparing the effects of efavirenz (EFV) versus rilpivirine (RPV) on endothelial function in a total of 40 HIV-uninfected healthy volunteers (20 in each arm) at the Indiana University Medical Center. Enrolled subjects will have their brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and other cardiovascular, inflammatory, and oxidative stress parameters measured at baseline and again after 4 weeks of study treatment.

Official Title
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A Randomized Controlled Trial Comparing Efavirenz With Rilpivirine on Changes in Endothelial Function, Inflammatory Markers, and Oxidative Stress in HIV-uninfected Healthy Volunteers

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Efavirenz
* Drug: Rilpivirine


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 For men who are capable of impregnating a female sexual partner, a willingness to use condoms with spermicidal gel for all sexual contacts during the course of the study No documented history of or receipt of medications being used to treat any psychiatric disorder, including (but not limited to) depression, dysthymia, mania, bipolar disease, schizophrenia, or previous suicidal ideation/attempts No anticipated changes or additions to other medical therapies during the course of the study No documented history of seizure disorder Exclusion Criteria: Inability to provide written, informed consent Known allergy/intolerance to rilpivirine, efavirenz, 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 Serum glucose > 200mg/dL at screening Serum total cholesterol > 190mg/dL at screening Breastfeeding at screening or during the course of the study Hypotension, defined as SBP < 90mmHg at time of each main study visit before brachial artery ultrasound measurements Hypertension, defined as SBP > 160mmHg at time of screening Receipt of investigational agents within 30 days of each screening visit or anticipated use during the trial Receipt of cytotoxic chemotherapy within 30 days of each screening visit or anticipated use during the trial Receipt of systemic glucocorticoids (> 10mg/day of prednisone or the equivalent), inhaled/nasal/topical fluticasone, or anabolic steroids within 30 days of each screening visit or anticipated use during the trial 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 or study personnel, 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 45 days of screening Drugs/therapies with significant CYP 450 induction or inhibition potential at screening Use of antacids, H2-blockers, or proton pump inhibitors within 30 days of screening or anticipated use of these drugs during the trial Any history of injection or illicit drug use Presence of fever, defined as an oral or tympanic temperature > 100.3F, at either the Entry or Closeout Visits On the PHQ-9 depression questionnaire at screening, a total score of more than 9 or any score over 0 on question 9.

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Efavirenz<br>Efavirenz 600mg given nightly without food for 30 days | Drug: Efavirenz<br>* 600mg orally every evening<br>* Other names: Sustiva, Stocrin;|
| Active Comparator: Rilpivirine<br>Rilpivirine 25mg given daily with meals for 30 days | Drug: Rilpivirine<br>* 25mg orally once daily<br>* Other names: Edurant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flow-mediated Dilation of the Brachial Artery | This is a measure of in vivo endothelial function | Change from baseline to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Markers | Change in high sensitivity C-reactive protein levels | Change from baseline to 4 weeks | 
| Endothelial Activation Markers | Change in soluble vascular cell adhesion molecule-1 levels | Change from baseline to 4 weeks | 
| Oxidative Stress Markers | Change in F2-isoprostane levels | Change from baseline to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelium, inflammation, oxidative stress, HIV-1