Sildenafil to Treat HIV-Associated Pulmonary Hypertension

NCT00327080 | Terminated Phase 1

• 2 other identifiers: 06016506-H-0165
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

HIV

Keywords

HIV; AIDS; Pulmonary Hypertension; Blood Flow Studies; Right Heart Catheterization; HIV Infection; HIV Associated Pulmonary Hypertension; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Evaluate pulmonary artery and systemic endothelial function in HIV infected volunteers with pulmonary hypertension in comparison to HIV infected volunteers without pulmonary hypertension.

Secondary Outcomes (1)

• Evaluate the safety and efficacy of sildenafil in the treatment of hemodynamic and functional abnormalities in volunteers with HIV associated pulmonary hypertension.

Interventions

MRI PROCEDURE

L-NMMA DRUG

Acetylcholine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• For Healthy Volunteers:
• Males or females, 18 years of age or older.
• No history of HIV infection.
• EKG and echocardiogram with no evidence of clinical relevant heart disease (including TRV less than 2.5 m/s)
• No history of causes of pulmonary hypertension such as collagen vascular disease, chronic liver disease with ALT or AST greater than 2 times the upper limit of normal or cirrhosis of the liver, chronic thromboembolic disease, congenital heart defects, or pulmonary parenchymal disease with hypoxemia.
• No history of diseases thought to be related to development of endothelial dysfunction including systemic hypertension or diabetes requiring drug therapy, hypercholesterolemia and obesity.
• No history of anemia, thrombocytopenia or coagulopathy.
• No history of renal insufficiency.
• No medical conditions requiring chronic medication use with the exception of:
• Heartburn, GERD
• Environmental allegeries, post nasal drip or non-allergic rhinitis
• Asthma with no history of oral steroid use, weekly inhaled steroids, or hospitalization for asthma exacerbation.
• Dermatologic conditions that do not require the use of oral steroids or other immunosuppressants.
• No more than 20 cigarettes per year for the previous 2 years and no cigarette use for 30 days prior to the screening evaluation until completion of the study.
• For HIV Positive Volunteers:

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, Hirschel B, Luthy R. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med. 1997 Mar;155(3):990-5. doi: 10.1164/ajrccm.155.3.9117037.

  PMID: 9117037 BACKGROUND

• Zuber JP, Calmy A, Evison JM, Hasse B, Schiffer V, Wagels T, Nuesch R, Magenta L, Ledergerber B, Jenni R, Speich R, Opravil M; Swiss HIV Cohort Study Group. Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis. 2004 Apr 15;38(8):1178-85. doi: 10.1086/383037. Epub 2004 Apr 1.

  PMID: 15095226 BACKGROUND

• Nunes H, Humbert M, Sitbon O, Morse JH, Deng Z, Knowles JA, Le Gall C, Parent F, Garcia G, Herve P, Barst RJ, Simonneau G. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2003 May 15;167(10):1433-9. doi: 10.1164/rccm.200204-330OC. Epub 2003 Feb 25.

  PMID: 12615632 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Hypertension, Pulmonary; HIV Infections

Interventions

omega-N-Methylarginine; Acetylcholine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Biogenic Amines; Amines; Organic Chemicals

Study Officials

• Henry Masur, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 17, 2006
• First Posted: May 18, 2006
• Study Start: May 12, 2006
• Primary Completion: March 18, 2009
• Study Completion: March 18, 2009
• Last Updated: December 17, 2019

Record last verified: 2012-11-13

Locations

US (1)