Clinical trial NCT00708565: Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction and Exercise Capacity at High Altitude
Official title: Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction and Exercise Capacity at High Altitude
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hypoxic Pulmonary Vasoconstriction
Keywords: To study the effects of iloprost on hypoxic pulmonary vasoconstriction at high altitude
Lead sponsor: VA Loma Linda Health Care System
Sponsor class: FED
Collaborators: name: Actelion
First posted: 2008-07-02
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to determine if single dose administration of inhaled iloprost will reduce pulmonary artery pressure, reduce hypoxic pulmonary vasoconstriction and improve arterial oxygenation at rest and during exercise at high altitude.

Detailed description: Three major pathways in addition to oxygen modulate pulmonary vascular tone: 1) nitric oxide, 2) endothelin, and 3) prostacyclin. Considerable animal data support the role of the prostacyclin pathway in modulating hypoxic pulmonary vasoconstriction. In humans, prostacyclin and its analogs are important therapeutic agents in the treatment of pulmonary arterial hypertension (PAH). Despite the animal data and human data in PAH there is very little information about the use of iloprost to relieve hypoxic pulmonary vasoconstriction in healthy humans. Inhaled iloprost is an ideal agent to study the prostacyclin pathway due to its short duration of action (30-90 min) and elimination half-life of only 20-30 min. Individuals already participating in the Nepal Medex 2008 trip will be invited to participate in this research. Participants will be healthy active females or males, between 18-80 years of age, without known pregnancy or liver disease, who have a readily measurable tricuspid regurgitant velocity by Doppler echocardiography. If possible, we will attempt to identify a cohort of HAPE susceptible patients. Participants will undergo evaluation both at sea level (baseline) and at high altitude. Baseline (low altitude) testing will be performed in Bangor, North Wales, UK, and will include evaluation of pulmonary artery systolic pressures, cardiac output, and oxygen saturation at rest and during submaximal exercise before and after inhalation of iloprost. This strategy will then be repeated at an altitude of approximately 5000 meters in the Dhaulagiri region of Nepal.

Eligibility criteria: Inclusion Criteria:

1. Age: 18 - 80 years
2. Healthy physically active males or females
3. Have readily measurable tricuspid regurgitation (TR) peak systolic velocity by continuous wave Doppler ultrasound

Exclusion Criteria:

1. Unable to measure TR velocity
2. Known liver disease
3. Pregnancy
4. Nitrates, cyclosporin, glyburide or other medications that in the opinion of the investigators could place subjects at increased risk of complications
5. Any other medical condition that in the opinion of the investigators would place the subject at high risk

Primary outcomes:
measure: Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation
timeFrame: 6 months
Secondary outcomes:
measure: Heart rate, tissue Doppler echocardiographic measurements
timeFrame: 6 months
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Jerry L. Pettis VA Medical Center
state: California
Study officials:
affiliation: Jerry L. Pettis VA Mecial Center
name: James D Anholm, MD
role: PRINCIPAL_INVESTIGATOR
References: