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

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

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

Study Overview

• Status: Completed
• Conditions: HIV Infections; Inflammation; Insulin Resistance; Endothelial Function; Lipids
• Intervention / Treatment: Drug: Etravirine

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Infectious Diseases Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Investigators: Principal Investigator: Samir K Gupta, MD, MS, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: March 27, 2009
• First Submitted That Met QC Criteria: March 27, 2009
• First Posted (Estimate): March 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 7, 2011
• Last Update Submitted That Met QC Criteria: January 5, 2011
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: HIV; Endothelial function; Etravirine
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Inflammation; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Etravirine
• Other Study ID Numbers: 0812-18 (TMC125HIV4003)