Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction and Exercise Capacity at High Altitude

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.

Study Overview

• Status: Unknown
• Conditions: Hypoxic Pulmonary Vasoconstriction
• Intervention / Treatment: Drug: iloprost

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92357
      • Recruiting
      • Jerry L. Pettis VA Medical Center
      • Contact: James D Anholm, MD; Phone Number: 909-583-6098; Email: James.Anholm@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Heart rate, tissue Doppler echocardiographic measurements	6 months

Collaborators and Investigators

• Sponsor: VA Loma Linda Health Care System
• Collaborators: Actelion
• Investigators: Principal Investigator: James D Anholm, MD, Jerry L. Pettis VA Mecial Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Anticipated): October 1, 2008
• Study Completion (Anticipated): October 1, 2008

Study Registration Dates

• First Submitted: June 30, 2008
• First Submitted That Met QC Criteria: July 1, 2008
• First Posted (Estimate): July 2, 2008

Study Record Updates

• Last Update Posted (Estimate): July 2, 2008
• Last Update Submitted That Met QC Criteria: July 1, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: To study the effects of iloprost on hypoxic pulmonary vasoconstriction at high altitude
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: 00769