Sildenafil to Treat HIV-Associated Pulmonary Hypertension
Status:
Terminated
Trial end date:
2009-03-18
Target enrollment:
Participant gender:
Summary
This study will examine how blood pressure in the lungs is controlled in healthy people,
people with HIV and people with HIV and pulmonary artery hypertension (high blood pressure in
the lungs, also called PAH). PAH sometimes develops in people with HIV, but it is not known
why this occurs or how best to treat it.
Healthy volunteers and patients with HIV infection who are 18 years of age or older may be
eligible for this study. All candidates are screened with a medical history, physical
examination, electrocardiogram (EKG), chest x-ray, echocardiogram and blood tests.
Participants undergo the following procedures:
All participants have a right heart catheterization and forearm blood flow study.
- Catheterization study. A catheter (plastic tube) is placed in an arm vein and possibly
in an artery in the arm. Then a large catheter is passed through a vein in the groin,
neck or chest. Through this "introducer" catheter, another catheter is advanced into the
right side of the heart and to the pulmonary artery. A facemask is put in place to
measure the amount of nitric oxide produced by the lungs. Acetylcholine is infused
through the catheter and its effects on blood pressure in the lungs and on the amount of
nitric oxide exhaled is measured. After about 1 hour, the catheter and facemask are
removed and a new catheter is inserted through the introducer catheter into the
pulmonary artery. The subject is moved into an MRI scanner where blood flow is measured
after infusion of three different medications: acetylcholine (causes blood vessels to
expand and slows heart rate); sodium nitroprusside (causes blood vessels to expand and
increases blood flow to the heart); and L-NMMA (decreases blood flow by blocking
production of nitric oxide in cells lining the blood vessels).
- Blood flow study. Small tubes are inserted into the artery of the patient's forearm.
These are used to infuse medicines and draw blood samples. Forearm blood flow is
measured using pressure cuffs placed on the wrist and upper arm, and a strain gauge (a
rubber band device) placed around the forearm. When the cuffs are inflated, blood flows
into the arm, stretching the strain gauge, and the flow measurement is recorded. A small
lamp is positioned over the hand to measure the light reflected from the hand and blood
flow in the forearm. Blood samples are then drawn to measure blood counts and proteins
and other natural body chemicals. Then, forearm blood flow is measured after
administration of small doses of sodium nitroprusside, acetylcholine and L-NMMA. There
is a 20- to 30-minute rest period between injections of the different drugs.
In addition, HIV-infected patients with PAH undergo the following tests to determine the
cause of their PAH: CT scan of the lungs, pulmonary function tests, 6-minute walk test,
quality-of-life assessment, assessment of difficulty in breathing, exercise testing while
measuring oxygen breathed in and carbon dioxide breathed out, blood tests, monitoring of
oxygen saturation during sleep for 1 night and ventilation/perfusion scan. For the
ventilation/perfusion scan, the subject breathes in a small amount of radioactive aerosol
while images are obtained of the radioactivity as it enters the lungs, and then pictures of
the lungs are taken from multiple angles. Next, the patient receives an injection of tiny
particles of albumin (a protein) containing a small amount of radioactivity and pictures of
the lungs are taken that show the pattern of blood flow to the lungs.
Patients with HIV and PAH who may benefit from the investigational drug, sildenafil (commonly
known as Viagra), may continue to participate in the next stage of the study. They receive
the first dose of sildenafil after completing the forearm blood flow study. They continue the
drug for 16 weeks, returning to the clinic 1 week after the first dose and then every other
week to monitor the response to treatment and drug side effects. At the end of 16 weeks,
patients return to the clinic for a repeat evaluation, including blood tests, 6-minute walk
test, echocardiogram, right heart catheterization and forearm blood flow study.
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