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

Sponsor

Indiana University (Other)

Overall Status

Completed

CT.gov ID

NCT00720590

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endothelial Dysfunction	Drug: Atazanavir Drug: Lopinavir/ritonavir Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Other

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

Study Start Date :

Nov 1, 2003

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Leg blood flow response to the intra-femoral artery infusion of methacholine chloride [Measured at Week 4]

Secondary Outcome Measures

Insulin sensitivity measured by the hyperinsulinemic euglycemic clamp study [Measured at Week 4]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

Indiana University
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator: Michael P. Dubé, MD, Indiana University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00720590

Other Study ID Numbers:

573
R01HL072711
R01HL072711-01

First Posted:

Jul 23, 2008

Last Update Posted:

Oct 25, 2017

Last Verified:

Jul 1, 2008

Additional relevant MeSH terms:

Ritonavir

Lopinavir

Atazanavir Sulfate

Study Results

No Results Posted as of Oct 25, 2017