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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
  Purpose

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.


Condition Intervention
Endothelial Dysfunction
Drug: Atazanavir
Drug: Lopinavir/ritonavir
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Effect of HIV-1 Protease Inhibitors on Endothelial Function and Glucose Metabolism in Normal, HIV-Uninfected Subjects: Atazanavir or Lopinavir/Ritonavir or Placebo

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: November 2003
Study Completion Date: October 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive treatment with atazanavir and placebo lopinavir/ritonavir.
Drug: Atazanavir
400 mg of atazanavir (two 200-mg capsules) per day for 4 weeks
Drug: Placebo
Daily dose of placebo for 4 weeks
Experimental: 2
Participants will receive treatment with lopinavir/ritonavir and placebo atazanavir.
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
Placebo Comparator: 3
Participants will receive treatment with placebos for both drugs.
Drug: Placebo
Daily dose of placebo for 4 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  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: NCT00720590

Locations
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Investigators
Principal Investigator: Michael P. Dubé, MD Indiana University School of Medicine
  More Information

Publications:
Responsible Party: Michael P. Dubé, MD, Indiana University School of Medicine
ClinicalTrials.gov Identifier: NCT00720590     History of Changes
Other Study ID Numbers: 573, R01 HL072711-01
Study First Received: July 21, 2008
Last Updated: August 29, 2008
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Atazanavir
HIV Protease Inhibitors
Lopinavir
Protease Inhibitors
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014