The Effect of Lopinavir/Ritonavir on Endothelial Function
Status:
Completed
Trial end date:
2005-09-01
Target enrollment:
Participant gender:
Summary
This study will examine how the anti-HIV protease inhibitor lopinavir/ritonavir (Kaletra®
(Registered Trademark)) affects the function of the endothelium (lining of the arteries).
Medications such as protease inhibitors can dramatically change the course of HIV infection
in many patients; however, among their side effects is development of abnormal lipid levels
resulting in high cholesterol and insulin resistance. These side effects may damage the
lining of the arteries that supply blood to the heart, leading to premature coronary artery
disease. The study will determine whether lopinavir/ritonavir directly affects endothelial
function and whether it alters cholesterol levels, glucose tolerance, and markers of
inflammation in people who take the drug for 4 weeks.
Healthy normal volunteers between 18 and 40 years of age may be eligible for this study.
Candidates must be HIV-negative and have no history of heart disease, hypertension, or
diabetes mellitus. They must not have smoked for at least 6 weeks before entering the study.
Volunteers will be screened with a medical history, physical examination, blood tests
(including a pregnancy test for women of childbearing potential), and electrocardiogram. In
addition, candidates will have an oral glucose tolerance test (see description below).
Participants will undergo the following procedures:
- Lopinavir/ritonavir: 4 weeks (3 capsules twice a day) beginning study day 1
- Flow-mediated vasodilatation test (study days 0 and 29) - An ultrasound device for
measuring the size of the brachial artery (artery in the upper arm) is placed just above
the elbow. The size of the artery is measured before and 5 minutes after blood flow to
the arm is stopped for 5 minutes, using a blood pressure cuff. The artery is also
measured before and after taking nitroglycerin, a medicine that dilates blood vessels.
These measurements tell how well the drug treatment works on the cells lining the
brachial artery, which is an indicator of coronary artery function. This test takes
about 1.5 hours.
- Forearm blood-flow test (study days 1 and 30): Small tubes are inserted into an artery
and vein in the forearm at the inside of the elbow. Blood pressure cuffs are placed
around the upper arm and wrist, and a strain gauge (a rubber band-like device) is placed
around the forearm. When the blood pressure cuffs are inflated, blood flows into the
forearm, stretching the strain gauge at a rate proportional to the blood flow. When the
devices are in place, a salt water solution is injected in the small tube in the artery.
After 20 minutes, small doses of the following drugs are given through the catheter at
various intervals: 1) L-NMMA (blocks production of nitric oxide, a substance produced by
the blood vessels that causes them to dilate); 2) sodium nitroprusside (dilates blood
vessels, increasing blood flow); 3) acetylcholine (lowers blood pressure); and 4)
acetylcholine plus L-NMMA. The effect of the different drugs on blood flow in the
forearm is measured. The study takes about 2 hours to complete.
- Blood tests (screening and study days 1,15, 30, and 44)
- Electrocardiogram (at screening and on study day 30)
- Oral glucose tolerance test (at screening and on study day 30) - A blood sample is
collected. Then, the subject drinks 300 milliliters of a glucose solution (a liquid that
contains sugar dissolved in water). Two hours after drinking the solution, blood is
drawn again to examine how the body responds to the increase blood sugar levels.
Phase:
Phase 1
Details
Lead Sponsor:
National Institutes of Health Clinical Center (CC)