Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress
- Registration Number
- NCT01585038
- Lead Sponsor
- Indiana University
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rilpivirine Rilpivirine Rilpivirine 25mg given daily with meals for 30 days Efavirenz Efavirenz Efavirenz 600mg given nightly without food for 30 days
- Primary Outcome Measures
Name Time Method Change in Flow-mediated Dilation of the Brachial Artery Change from baseline to 4 weeks This is a measure of in vivo endothelial function
- Secondary Outcome Measures
Name Time Method Inflammatory Markers Change from baseline to 4 weeks Change in high sensitivity C-reactive protein levels
Endothelial Activation Markers Change from baseline to 4 weeks Change in soluble vascular cell adhesion molecule-1 levels
Oxidative Stress Markers Change from baseline to 4 weeks Change in F2-isoprostane levels
Trial Locations
- Locations (1)
Indiana Clinical and Translational Sciences Institute
🇺🇸Indianapolis, Indiana, United States