Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors
| Tracking Information | |||||
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| First Received Date ICMJE | July 21, 2008 | ||||
| Last Updated Date | August 29, 2008 | ||||
| Start Date ICMJE | November 2003 | ||||
| Primary Completion Date | September 2006 (final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ] | ||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | Complete list of historical versions of study NCT00720590 on ClinicalTrials.gov Archive Site | ||||
| Current Secondary Outcome Measures ICMJE |
Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ] | ||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Effect of the HIV Protease Inhibitors Atazanavir and Lopinavir/Ritonavir on Cardiovascular Disease Risk Factors | ||||
| Official Title ICMJE | Effect of HIV-1 Protease Inhibitors on Endothelial Function and Glucose Metabolism in Normal, HIV-Uninfected Subjects: Atazanavir or Lopinavir/Ritonavir or Placebo | ||||
| Brief Summary | 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. |
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| Detailed Description | 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. |
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| Study Type ICMJE | Interventional | ||||
| Study Phase | Not Provided | ||||
| Study Design ICMJE | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) |
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| Condition ICMJE | Endothelial Dysfunction | ||||
| Intervention ICMJE |
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| Study Arm (s) |
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| Publications * | 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. | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Enrollment ICMJE | 30 | ||||
| Completion Date | October 2006 | ||||
| Primary Completion Date | September 2006 (final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria: |
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| Gender | Male | ||||
| Ages | 18 Years to 65 Years | ||||
| Accepts Healthy Volunteers | Yes | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Location Countries ICMJE | United States | ||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT00720590 | ||||
| Other Study ID Numbers ICMJE | 573, R01 HL072711-01 | ||||
| Has Data Monitoring Committee | Yes | ||||
| Responsible Party | Michael P. Dubé, MD, Indiana University School of Medicine | ||||
| Study Sponsor ICMJE | National Heart, Lung, and Blood Institute (NHLBI) | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| Information Provided By | National Heart, Lung, and Blood Institute (NHLBI) | ||||
| Verification Date | July 2008 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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