Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Evaluating the Effectiveness of Pentoxifylline at Improving Blood Vessel Function in HIV-infected People Not Receiving Antiretroviral Medications

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Samir Gupta, Indiana University
ClinicalTrials.gov Identifier:
NCT00796822
First received: November 21, 2008
Last updated: May 20, 2013
Last verified: May 2013

November 21, 2008
May 20, 2013
January 2009
October 2011   (final data collection date for primary outcome measure)
Change in Flow-mediated Dilation of the Brachial Artery [ Time Frame: Measured at baseline and Week 8 ] [ Designated as safety issue: No ]
Flow-mediated dilation is nn in vivo measure of arterial endothelial function. We assessed changes in flow-mediated dilation from baseline to week 8.
Flow-mediated dilation of the brachial artery [ Time Frame: Entry, week 4, week 8 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00796822 on ClinicalTrials.gov Archive Site
  • Immunologic Parameters (i.e., Activated CD8 Cell Percentage, CD4 Cell Count) [ Time Frame: Measured at baseline and Weeks 4 and 8 ] [ Designated as safety issue: No ]
  • Inflammatory Biomarkers (i.e., MCP-1, sVCAM-1, IP-10, MMP-9, TIMP-1, PAI-1 Active, hsCRP) [ Time Frame: Measured at baseline and Weeks 4 and 8 ] [ Designated as safety issue: No ]
  • Metabolics (i.e., Fasting Lipid Profile, Glucose, Insulin) [ Time Frame: Measured at baseline and Weeks 4 and 8 ] [ Designated as safety issue: No ]
  • Safety and Tolerability [ Time Frame: Measured at Weeks 4 and 8 ] [ Designated as safety issue: Yes ]
  • Immunologic parameters (activated CD8 cell percentage, CD4 cell count) [ Time Frame: Entry, week 4, week 8 ] [ Designated as safety issue: No ]
  • Inflammatory biomarkers (MCP-1, sVCAM-1, IP-10, MMP-9, TIMP-1, PAI-1 active, hsCRP) [ Time Frame: Entry, week 4, week 8 ] [ Designated as safety issue: No ]
  • Metabolics (fasting lipid profile, glucose, insulin) [ Time Frame: Entry, week 4, week 8 ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Week 4, week 8 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Evaluating the Effectiveness of Pentoxifylline at Improving Blood Vessel Function in HIV-infected People Not Receiving Antiretroviral Medications
A Randomized, Placebo-Controlled Trial of Pentoxifylline to Improve Endothelial Function in HIV-Infected Patients Not Requiring Antiretroviral Therapy

People infected with HIV have a greater risk of developing cardiovascular disease than people not infected with HIV. This may be due to increased inflammation brought on by either the HIV infection itself or the use of antiretroviral medications to treat HIV infection. This study will evaluate an anti-inflammatory drug, pentoxifylline, to determine whether it improves blood vessel function and reduces inflammation in people infected with HIV who are not currently receiving antiretroviral medications.

People infected with HIV have an increased risk for cardiovascular disease, which is a leading cause of death for those with HIV. The increase in cardiovascular disease has been thought to be linked to the use of several types of antiretroviral medications used to treat HIV infection. These medications have been shown to cause insulin resistance and dyslipidemia, or high cholesterol levels—conditions that can lead to atherosclerosis, which is a build-up of plaque within the arteries, and ultimately to cardiovascular disease. However, new research is emerging that suggests that people infected with HIV who do not receive antiretroviral medications may also have an increased risk of cardiovascular disease as a result of increased endothelial dysfunction. This condition, which involves malfunctioning of the thin layer of cells that line the interior surface of blood vessels, can lead to atherosclerosis and cardiovascular disease. Pentoxifylline is a medication that is currently used to reduce leg pain in people with blockages in the blood vessels in their legs. Previous research has shown that pentoxifylline may reduce inflammation and improve blood vessel function in people infected with HIV, but more research is needed to confirm these benefits. The purpose of this study is to determine whether pentoxifylline reduces inflammation and improves endothelial function in HIV-infected people who are not receiving antiretroviral medications.

This study will enroll HIV-infected people who are not currently receiving antiretroviral medications. At a baseline study visit, participants will undergo a medical history review; physical examination; measurements in blood pressure, heart rate, height, weight, waist, and hip; and blood and urine collection. An ultrasound imaging test of the arm will measure blood vessel function. Participants will then be randomly assigned to receive either pentoxifylline or placebo three times a day for 8 weeks. At study visits at Weeks 4 and 8, participants will undergo repeat baseline measurements.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV
  • Cardiovascular Diseases
  • Atherosclerosis
  • Drug: Pentoxifylline
    400 mg three times a day for 8 weeks
  • Drug: Placebo
    One pill three times a day for 8 weeks
  • Experimental: 1
    Participants will receive pentoxifylline.
    Intervention: Drug: Pentoxifylline
  • Placebo Comparator: 2
    Participants will receive placebo.
    Intervention: Drug: Placebo
Gupta SK, Mi D, Dubé MP, Saha CK, Johnson RM, Stein JH, Clauss MA, Mather KJ, Desta Z, Liu Z. Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial. PLoS One. 2013 Apr 9;8(4):e60852. doi: 10.1371/journal.pone.0060852. Print 2013.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
October 2011
October 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Documentation of HIV infection with a positive HIV enzyme-linked immunosorbent assay (ELISA) test and confirmatory western blot test
  • CD4 cell count greater than 350/µL at the time of screening
  • Has not received any antiretroviral therapies in the 6 months before screening
  • No anticipated need for any antiretroviral therapies during the course of this study, as determined by the principal investigator or by the participant's HIV caregiver

Note: There is no HIV-1 RNA level eligibility criterion.

Exclusion Criteria:

  • Incarceration at the time of screening or at any study visit
  • Diagnosed vascular disease, including history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease
  • Diagnosed disease or process, other than HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, or other collagen vascular diseases). Hepatitis B or C co-infections are NOT exclusionary.
  • History of bleeding diathesis, gastrointestinal ulceration or bleeding, cerebrovascular aneurysm or bleeding, or retinal hemorrhage
  • Known or suspected cancer requiring systemic treatment in the 6 months before screening
  • History of American Diabetes Association (ADA)-defined diabetes mellitus. History of gestational diabetes is not exclusionary if the potential participant does not have current ADA-defined diabetes.
  • History of migraine headaches
  • History of Raynaud's phenomenon
  • History of cardiac arrhythmias or cardiomyopathy
  • History of hypothyroidism or hyperthyroidism, even if treated
  • Known allergy or intolerance to pentoxifylline or other methylxanthines (e.g., theophylline, caffeine, theobromine). Use of caffeinated products, except on the mornings of the study visits, is not exclusionary.
  • Known allergy or intolerance to nitroglycerin
  • History of carotid bruits
  • Creatinine clearance less than 50 mL/min, using the Cockcroft-Gault equation and a serum creatinine level measured in the 28 days before screening or at the screening visit
  • Hemoglobin less than 9.0 mg/dL in the 28 days before screening or at the screening visit
  • Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) greater than three times the upper limit of normal (ULN) in the 28 days before screening or at the screening visit
  • Total bilirubin greater than 2.5 times the ULN in the 28 days before screening or at the screening visit
  • Fever, defined as a temperature greater than or equal to 38.0 C in the 48 hours before screening. Fever in the 48 hours before each study visit will require postponement of that study visit until the participant's temperature has been lower than 38.0 C for at least 48 hours; fevers continuing past the allowed study visit timeframe will result in study discontinuation.
  • Therapy for acute infection or other serious medical illnesses in the 14 days before screening. Therapy for acute infection or other serious medical illnesses that overlaps with a study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.
  • Pregnant or breastfeeding
  • Hypotension, defined as systolic blood pressure less than 90 mm Hg, at time of screening. Hypotension noted prior to brachial artery reactivity testing at each study visit will result in study visit postponement of at least 1 day until systolic pressure is greater than or equal to 90 mm Hg the morning of brachial reactivity testing; postponement outside of the allowed study visit timeframe will result in study discontinuation.
  • Hypertension, defined as the receipt of any antihypertensive medication in the 28 days before screening or systolic blood pressure greater than 160 mm Hg at the screening visit
  • Receipt of anti-inflammatory agents (including, but not limited to, plaquenil, infliximab, etanercept, mycophenolate mofetil, sirolimus, tacrolimus, cyclosporine, pentoxifylline, or thalidomide) in the 28 days before screening
  • Receipt of investigational agents, cytotoxic chemotherapy, systemic or topical glucocorticoids (of any dose), or anabolic steroids in the 28 days before screening. Physiologic testosterone replacement therapy is not exclusionary.
  • Receipt of lipid-lowering drugs, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDS), acetazolamide, anticoagulants, anticonvulsants, or thyroid replacements in the 28 days before screening
  • Use of sildenafil, vardenafil, or tadalafil in the 72 hours before or after each study visit
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00796822
614, R01HL095149-01, R01 HL095149-01
Yes
Samir Gupta, Indiana University
Indiana University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Samir K. Gupta, MD, MS Indiana University School of Medicine
Indiana University
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP