Endothelial Dysfunction as a Risk Factor in HIV Study
Highly active antiretroviral therapy (HAART) has proven effective in altering the natural history of HIV infection in many patients. However, this therapy may not be sustainable because of the toxicities of the medications. Evidence suggests that HIV-infected patients on HAART may be at risk for premature coronary artery disease. The exact cause is unknown. It is possible that the medications directly affect the endothelium (the lining of the arteries that supply blood to the heart) and lead to premature heart disease. Or because the medications cause lipid abnormalities (high cholesterol) and a condition of relative insulin resistance, in which the body has a difficult time processing sugars; known risk factors for endothelial dysfunction and heart disease. Therapeutic intervention that reverses these lipid abnormalities and/or insulin resistance may lower these risk factors, normalize endothelial function, and decrease the risk of heart disease.
This protocol aims to assess endothelial function among a group of HIV-infected patients with varying degrees of viral activity and levels of immune function on a variety of HAART regimens. It also aims to evaluate the effect of three different medications on lipids, insulin resistance, and thus endothelial function. Understanding the factors involved in causing endothelial dysfunction will help better characterize the relative risks and benefits of early versus late and continuous versus intermittent HAART therapy. The research may offer some insights into the causes of premature heart disease among HIV-infected patients on HAART that could be more thoroughly investigated in subsequent clinical trials.
A total of 75 patients will be recruited: 25 for each arm of the study. Each arm evaluates the potential benefit of a particular medication and will enroll sequentially. An endothelial function test will be performed on an outpatient basis. The first 25 patients will be assigned at random to receive pravastatin sodium or placebo; the next 25 will receive gemfibrozil or placebo; the final 25 will receive rosiglitazone or placebo. Patients will take the pills for 6 weeks, no pills for the next 4 weeks, and then the opposite treatment for 6 more weeks. Two weeks after the start of the study drug, blood will be taken to check for potential toxic side effects. After each 6-week treatment, blood will be drawn and endothelial function tests will be performed.
|HIV Infections||Drug: Pravastatin Drug: Gemfibrozil Drug: Rosiglitazone||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Endothelial Dysfunction as a Risk Factor in HIV Study|
|Study Start Date:||May 2002|
|Estimated Study Completion Date:||October 2005|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00039663
|United States, Maryland|
|National Institutes of Health Clinical Center (CC)|
|Bethesda, Maryland, United States, 20892|