Effects of Etravirine on Endothelial Function in HIV-uninfected Adults: A Pilot Study
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Purpose
The purpose of this study is to determine the safety and effects of etravirine, an HIV antiretroviral medication, on vascular function.
| Condition | Intervention | Phase |
|---|---|---|
|
Endothelial Function Lipids Insulin Resistance Inflammation HIV Infections |
Drug: Etravirine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label |
| Official Title: | Effects of Etravirine (INTELENCETM) on Endothelial Function in HIV-uninfected Adults: A Pilot Study |
- Flow-mediated Dilation (FMD) of the Brachial Artery [ Time Frame: Entry and four weeks ] [ Designated as safety issue: Yes ]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.
- Lipid Fractions [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
- Insulin Sensitivity [(Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)] [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
- Blood Pressure [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
- Inflammatory Biomarkers [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
- Endothelial Activation Biomarkers [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
| Enrollment: | 28 |
| Study Start Date: | April 2009 |
| Study Completion Date: | July 2010 |
| Primary Completion Date: | March 2010 (Final data collection date for primary outcome measure) |
-
Drug: Etravirine
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
- No history of diabetes, hypertension, or dyslipidemia
- No anticipated changes or additions to other medical therapies during the course of the study
Exclusion Criteria:
- Inability to provide written, informed consent
- Known allergy/intolerance to etravirine 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
- Breastfeeding at screening and during the course of the study
- Hypotension, defined as SBP<90mmHg at time of each main study visit before brachial artery ultrasound measurements
- 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
- 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, 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 one year of screening.
Contacts and Locations| United States, Indiana | |
| Infectious Diseases Research Center | |
| Indianapolis, Indiana, United States, 46202 | |
| Principal Investigator: | Samir K Gupta, MD, MS | Indiana University School of Medicine |
More Information
No publications provided
| Responsible Party: | Samir K. Gupta, MD, MS, Indiana University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00871234 History of Changes |
| Other Study ID Numbers: | 0812-18 (TMC125HIV4003) |
| Study First Received: | March 27, 2009 |
| Results First Received: | December 7, 2010 |
| Last Updated: | January 5, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Indiana University:
|
HIV Endothelial function Etravirine |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Inflammation Insulin Resistance Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral |
Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Pathologic Processes Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases |
ClinicalTrials.gov processed this record on May 21, 2013