Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Janssen Services, LLC
Information provided by (Responsible Party):
Samir K Gupta, MD, MS, Indiana University
ClinicalTrials.gov Identifier:
NCT01585038
First received: April 23, 2012
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to compare the cardiovascular profiles of efavirenz and rilpivirine, which are two drugs used to treat HIV infection.


Condition Intervention Phase
Cardiovascular Disease
Drug: Efavirenz
Drug: Rilpivirine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Randomized Controlled Trial Comparing Efavirenz With Rilpivirine on Changes in Endothelial Function, Inflammatory Markers, and Oxidative Stress in HIV-uninfected Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Flow-mediated dilation of the brachial artery [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    This is a measure of in vivo endothelial function


Secondary Outcome Measures:
  • Inflammatory markers [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    hsCRP, IL-6, sTNFRI, sTNFRII

  • Endothelial activation markers [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    sVCAM-1, sICAM-1, vWF, IP-10

  • Oxidative stress markers [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    F2-isoprostane

  • Metabolic markers [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    HOMA-IR, fasting lipid profile


Estimated Enrollment: 40
Study Start Date: July 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Efavirenz Drug: Efavirenz
600mg orally every evening
Other Name: Sustiva, Stocrin
Active Comparator: Rilpivirine Drug: Rilpivirine
25mg orally once daily
Other Name: Edurant

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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. 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
  7. 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
  8. No anticipated changes or additions to other medical therapies during the course of the study
  9. No documented history of seizure disorder

Exclusion Criteria:

  1. Inability to provide written, informed consent
  2. Known allergy/intolerance to rilpivirine, efavirenz, 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. Serum glucose > 200mg/dL at screening
  9. Serum total cholesterol > 190mg/dL at screening
  10. Breastfeeding at screening or during the course of the study
  11. Hypotension, defined as SBP < 90mmHg at time of each main study visit before brachial artery ultrasound measurements
  12. Hypertension, defined as SBP > 160mmHg at time of screening
  13. Receipt of investigational agents within 30 days of each screening visit or anticipated use during the trial
  14. Receipt of cytotoxic chemotherapy within 30 days of each screening visit or anticipated use during the trial
  15. 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
  16. Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis), within 72 hours (before or after) of brachial artery reactivity testing
  17. Indwelling vascular catheters within any upper body vessel at time of brachial artery reactivity testing
  18. Active drug or alcohol use or dependence that, in the opinion of the investigator or study personnel, would interfere with adherence to study requirements
  19. 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
  20. History of migraine headaches
  21. History of Raynaud's phenomenon
  22. History of cardiac arrythmias
  23. History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH outside the normal range on most recent testing during normal clinical care)
  24. History of carotid bruits
  25. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or nicotine replacement treatments (patch, gum) within 45 days of screening
  26. Drugs/therapies with significant CYP 450 induction or inhibition potential at screening
  27. Use of antacids, H2-blockers, or proton pump inhibitors within 30 days of screening or anticipated use of these drugs during the trial
  28. Any history of injection or illicit drug use
  29. Presence of fever, defined as an oral or tympanic temperature > 100.3F, at either the Entry or Closeout Visits
  30. On the PHQ-9 depression questionnaire at screening, a total score of more than 9 or any score over 0 on question 9.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585038

Locations
United States, Indiana
Indiana Clinical and Translational Sciences Institute
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Janssen Services, LLC
Investigators
Principal Investigator: Samir K Gupta, MD, MS Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Samir K Gupta, MD, MS, Associate Professor of Medicine, Indiana University
ClinicalTrials.gov Identifier: NCT01585038     History of Changes
Other Study ID Numbers: TMC278HIV4002
Study First Received: April 23, 2012
Last Updated: April 28, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by Indiana University:
endothelium
inflammation
oxidative stress
HIV-1

Additional relevant MeSH terms:
Cardiovascular Diseases
Inflammation
Pathologic Processes
Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014