Endothelial Cell Dysfunction in Pulmonary Hypertension

NCT00098072 | Completed Phase 1

• 2 other identifiers: 05004105-CC-0041
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine and test healthy volunteers and patients with pulmonary hypertension to try to learn more about the disease and find better ways to detect, treat, and, if possible, slow progression. Pulmonary hypertension is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) rises above normal levels and may become life-threatening. Normal volunteers and patients with pulmonary hypertension 18 years of age and older may be eligible for this study. All candidates are screened with a review of their medical records. Normal volunteers also have a medical history, electrocardiogram, echocardiogram (heart ultrasound), and pulmonary function test, in which the subject breathes in and out of a tube that measures lung volume, mechanics and function. All participants undergo the following tests and procedures:

• Echocardiogram to measure heart function and blood pressure in the lungs. A small probe held against the chest uses sound waves to obtain pictures of the heart.
• Magnetic resonance imaging (MRI) to evaluate the heart's pumping action. Subjects lie on a stretcher that slides into a long, tube-shaped scanner. The machine uses a magnetic field and radio waves to obtain images of the heart.
• 6-minute walk to measure how far the subject can walk in 6 minutes. Subjects walk around the hospital for 6 minutes at a comfortable pace.
• Exercise testing to measure the ability to exercise and the subject's oxygen levels during exercise. Subjects exercise on a bike or treadmill while the oxygen and carbon dioxide they breathe are measured using a small device placed in the mouth.
• Right heart catheterization to measure pressure in the heart and lungs. A small catheter (plastic tube) is placed in an arm vein. A longer catheter called a central line is placed in a deeper vein in the neck or just below the neck, or in the leg or arm. A long, thin catheter that measures blood pressure directly is then inserted into the vein and advanced through the chambers of the heart into the lung artery to measure all the pressures in the heart and obtain blood samples.
• Genetic and protein studies. DNA, RNA, and proteins from blood samples are studied for genes and proteins that might predict the development or progression of pulmonary hypertension. In addition to the above, patients whose pulmonary hypertension was caused by a blood vessel injury undergo the tests described below. The right heart catheter inserted for the catheterization procedure remains in place to obtain measurements of the effects of nitric oxide and nitrite in the following procedures:
• Inhalation of nitric oxide (a gas naturally produced by cells lining arteries) at 30-minute intervals to examine its effect on lung and heart pressures.
• Inhalation of aerosolized nitrite at 5-minute intervals to measure its effects on lung and heart pressures.
• Inhalation of nitric oxide for up to 24 hours to obtain multiple measurements of its effect on lung and heart pressures.
• Blood draws for laboratory tests. In patients whose pulmonary hypertension was caused by a blood vessel injury, we also plan to follow response to standard therapy. After the initiation of standard therapy, we will restudy the same parameters (excluding NO and sodium nitrite studies) in these patients at approximately 4 months, and yearly for 5 years ...

Conditions

Secondary Pulmonary Arterial Hypertension

Keywords

Cytometry; Genes; Hypertension; Lung; Proteomics; Primary Pulmonary Hypertenion; PPH; Healthy Volunteers; HV

Outcome Measures

Primary Outcomes (1)

• Establish the best technique for CEC and PBMC identification, quantification, and isolation and EPC identification and quantification.

  genome-wide expression profiles

  one year

Study Arms (1)

Pilot

EXPERIMENTAL

Pilot

Procedure: Heart Catheterization

Interventions

Heart Catheterization PROCEDURE

Heart Catheterization and collection of samples

Pilot

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with IPAH
• Patients diagnosed with secondary pulmonary hypertension known to have histopathology similar to the primary form or PAH. Clinical conditions causing pulmonary hypertension with histopathology similar to the primary form are listed below.
• i. Eisenmenger Syndrome
• ii. Collagen vascular disease
• iii. Liver disease with portal hypertension
• iv. Toxin induced injury (anorexic agents, rapeseed oil)
• v. HIV disease
• vi. Sickle cell disease

You may not qualify if:

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• Pregnant women (all women of childbearing age will be required to have a screening urine or blood pregnancy test)
• Age less than 18 years
• Inability to provide informed written consent for participation in the study
• Mean PA less than or equal to 25mmHg or PVR less than 3 wood units
• PCW greater than 16 mmHg unless increase accounted for by increased transpulmonary gradient greater than or equal to 10 mmHg
• Patients receiving more than 1 year of oral therapy or more than 6 months of IV therapy.
• Patients diagnosed with pulmonary hypertension not known to have histopathology similar to the primary form. Etiologies are listed below.
• Congenital or acquired valvular or myocardial disease
• Pulmonary parasitic diseases
• Arterial hypoxemia with hypercapnea
• COPD with hypoxemia and forced expiratory volume/forced vital capacity (FEV1/FVC) greater than 2 standard deviations from normal
• Interstitial lung disease with reduced total lung capacity greater than 2 standard deviations from normal and infiltrates on chest x-ray
• Pulmonary thromboembolic disease as evidenced by lung perfusion scan or pulmonary angiogram, or intravenous drug abuse
• Pulmonary hypertension due to congenital abnormalities of the lungs, thorax and diaphragm

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991 Sep 1;115(5):343-9. doi: 10.7326/0003-4819-115-5-343.

  PMID: 1863023 BACKGROUND

• International PPH Consortium; Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet. 2000 Sep;26(1):81-4. doi: 10.1038/79226.

  PMID: 10973254 BACKGROUND

• Rubin LJ. Primary pulmonary hypertension. Chest. 1993 Jul;104(1):236-50. doi: 10.1378/chest.104.1.236. No abstract available.

  PMID: 8325077 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypertension

Interventions

Cardiac Catheterization

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Catheterization; Therapeutics; Investigative Techniques

Study Officials

• Michael A Solomon, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2004
• First Posted: December 3, 2004
• Study Start: May 17, 2000
• Primary Completion: July 8, 2009
• Study Completion: July 8, 2009
• Last Updated: May 7, 2026

Record last verified: 2026-01-09

Locations

US (1)