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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00871234
• Other study ID #: 0812-18 (TMC125HIV4003)
• Status: Completed
• Phase: Phase 1
• First received: March 27, 2009
• Last updated: January 5, 2011
• Start date: April 2009
• Est. completion date: July 2010

Study information

• Verified date: December 2010
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Endothelial Function
• HIV Infections
• Inflammation
• Insulin Resistance
• Lipids

Intervention

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

Locations

Country	Name	City	State
United States	Infectious Diseases Research Center	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Lipid Fractions		Four weeks	Yes
Secondary	Insulin Sensitivity [(Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)]		Four weeks	Yes
Secondary	Blood Pressure		Four weeks	Yes
Secondary	Inflammatory Biomarkers		Four weeks	Yes
Secondary	Endothelial Activation Biomarkers		Four weeks	Yes