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

• ClinicalTrials.gov Identifier: NCT00871234
• Recruitment Status: Completed
• First Posted: March 30, 2009
• Results First Posted: January 5, 2011
• Last Update Posted: January 7, 2011
• Sponsor: Indiana University
• Collaborator: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Information provided by: Indiana University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Endothelial Function; Lipids; Insulin Resistance; Inflammation; HIV Infections	Drug: Etravirine	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Effects of Etravirine (INTELENCETM) on Endothelial Function in HIV-uninfected Adults: A Pilot Study
• Study Start Date: April 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: July 2010

Arms and Interventions

Intervention Details:

• Drug: Etravirine
  Two one-hundred mg tablets orally twice daily for four weeks
  Other Name: INTELENCETM

Outcome Measures

Primary Outcome Measures :

1. Flow-mediated Dilation (FMD) of the Brachial Artery [ Time Frame: 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 Outcome Measures :

1. Lipid Fractions [ Time Frame: Four weeks ]
2. Insulin Sensitivity [(Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)] [ Time Frame: Four weeks ]
3. Blood Pressure [ Time Frame: Four weeks ]
4. Inflammatory Biomarkers [ Time Frame: Four weeks ]
5. Endothelial Activation Biomarkers [ Time Frame: Four weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Indiana

Infectious Diseases Research Center

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Investigators

• Principal Investigator: Samir K Gupta, MD, MS; Indiana University School of Medicine

More Information

• Responsible Party: Samir K. Gupta, MD, MS, Indiana University School of Medicine
• ClinicalTrials.gov Identifier: NCT00871234
• Other Study ID Numbers: 0812-18 (TMC125HIV4003)
• First Posted: March 30, 2009
• Results First Posted: January 5, 2011
• Last Update Posted: January 7, 2011
• Last Verified: December 2010

Keywords provided by Indiana University:

HIV; Endothelial function; Etravirine

Additional relevant MeSH terms:

Insulin Resistance; Inflammation; Pathologic Processes; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Etravirine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents