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Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00720590
First received: July 21, 2008
Last updated: August 29, 2008
Last verified: July 2008

July 21, 2008
August 29, 2008
November 2003
September 2006   (final data collection date for primary outcome measure)
Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00720590 on ClinicalTrials.gov Archive Site
Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors
Effect of HIV-1 Protease Inhibitors on Endothelial Function and Glucose Metabolism in Normal, HIV-Uninfected Subjects: Atazanavir or Lopinavir/Ritonavir or Placebo

HIV protease inhibitors (PIs) are a class of antiretroviral drugs used to inhibit viral replication. They do so by interfering with a key step in the replication process. Some HIV PIs have been associated with an increased risk of adverse cardiovascular side effects. Further study is needed, however, to assess the full extent of effect of newer HIV PIs, including atazanavir and lopinavir/ritonavir, on cardiovascular disease risk. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors in healthy people without HIV.

Antiretroviral therapy for HIV, particularly with the use of PIs, is associated with an increased risk of heart attack. Specific cardiovascular side effects seen with the use of some PIs include insulin resistance, abnormal blood lipid levels, and endothelial dysfunction (abnormalities in the cells that line the inner surface of blood vessels). Past studies have shown that treatment with indinavir, an older PI, results in significant endothelial dysfunction, which may be the main cause for the increase in cardiovascular risk. Indinavir is now seldom used in clinical practice, and the newer PIs atazanavir and combination lopinavir/ritonavir now account for nearly 70% of total PI use in the United States. It is not known what effect these new PIs have on endothelial dysfunction. This study will compare the effects of atazanavir, lopinavir/ritonavir, and placebo on certain cardiovascular disease risk factors, including abnormal glucose metabolism and endothelial dysfunction, in healthy people without HIV.

Participation in this study will last 4 weeks. All participants will undergo initial assessments that will include various vascular and metabolic evaluations. Body weight, height, basal heart rate, and systolic and diastolic blood pressure will also be measured. Participants will then be assigned randomly to receive 4 weeks of treatment with 400 mg of atazanavir per day plus placebo, 400 mg/100 mg of lopinavir/ritonavir twice per day plus placebo, or placebos for both drugs per day. Upon completing the 4 weeks of treatment, participants will repeat the initial assessments.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Endothelial Dysfunction
  • Drug: Atazanavir
    400 mg of atazanavir (two 200-mg capsules) per day for 4 weeks
  • Drug: Lopinavir/ritonavir
    400 mg/100 mg of lopinavir/ritonavir (three soft-gel capsules, each containing 133.3 mg lopinavir and 33.3 mg ritonavir) twice per day with food for 4 weeks
  • Drug: Placebo
    Daily dose of placebo for 4 weeks
  • Experimental: 1
    Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.
    Interventions:
    • Drug: Atazanavir
    • Drug: Placebo
  • Experimental: 2
    Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.
    Interventions:
    • Drug: Lopinavir/ritonavir
    • Drug: Placebo
  • Placebo Comparator: 3
    Participants will receive treatment with placebos for both drugs.
    Intervention: Drug: Placebo
Dubé MP, Shen C, Greenwald M, Mather KJ. No impairment of endothelial function or insulin sensitivity with 4 weeks of the HIV protease inhibitors atazanavir or lopinavir-ritonavir in healthy subjects without HIV infection: a placebo-controlled trial. Clin Infect Dis. 2008 Aug 15;47(4):567-74.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
October 2006
September 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy and lean with normal lipids
  • Not infected with HIV or viral hepatitis

Exclusion Criteria:

Male
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00720590
573, R01 HL072711-01
Yes
Michael P. Dubé, MD, Indiana University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Not Provided
Principal Investigator: Michael P. Dubé, MD Indiana University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
July 2008

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