Sildenafil to Treat HIV-Associated Pulmonary Hypertension

Stopped early · Phase 1

Conditions studied: HIV

In brief

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. ...

Key facts

Study ID: NCT00327080
Run by: National Heart, Lung, and Blood Institute (NHLBI)
People needed: 20
Starts: 2006-05-12
Expected to finish: 2009-03-18
Last updated by the study team: 2019-12-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

For Healthy volunteers:
Current pregnancy, lactation or women not currently using medically acceptable birth control. (All women of childbearing age will be required to have a screening urine or blood pregnancy test)
Contraindication to MRI scanning including individuals with the following devices:
A) Central nervous system aneurysm clips
B) Implanted neural stimulator
C) Implanted cardiac pacemaker or defibrillator prior to enrollment
D) Cochlear implant
E) Ocular foreign body (e.g. metal shavings)
F) Insulin pump
G) Metal shrapnel or bullet
Contraindications to MRI contrast agent administration:
Inability to provide informed written consent for participation in the study.
Chronic, medically refractory atrial tachyarrhythmias
Symptoms of heart failure
Mean PA greater than 25 mmHg or PVR greater than 1.5 wood units, or PCWP greater than 15 mmHg
History of recreational drug use with the exception of marijuana. No Marijuana use within 3 months of protocol screening through completion of the study.
Volunteers may be excluded if in the opinion of the study investigators they have a condition that may adversely affect the outcome of the study or the safety of the volunteer.
For HIV Positive Volunteers:
Current pregnancy, lactation or women not currently using medically acceptable birth control.
Active, untreated opportunistic infection with the exception of oral thrush or neoplasm with the exception of Kaposi's Sarcoma.
Any of the following medical conditions:
A) Severe renal insufficiency (on hemodialysis or serum creatinine greater than 2.5 mg/dl) or (CrCl less than 20 ml/min).
B) Severe coagulopathy (platelets less than 100,000, PT INR greater than 1.5, PTT greater than 40 s)
Chronic, medically refractory atrial tachyarrhythmias
Current recreational drug use or use within 4 weeks of protocol screening with the exception of marijuana

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.