Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction at Altitude

Phase 1

Withdrawn

• Conditions: Hypoxic Pulmonary Vasoconstriction
• Interventions: Drug: iloprost

• Registration Number: NCT00724321
• Lead Sponsor: Loma Linda University

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 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 Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-25
• Study First Submitted QC: 2008-07-28
• Study First Posted: 2008-07-29
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-17
• Last Update Posted: 2015-09-18

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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. Known liver disease
2. Pregnancy
3. Medications that in the opinion of the investigators could place subjects at increased risk of complications Any other medical condition that in the opinion of the investigators would place the subject at high risk

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Iloprost and placebo	iloprost	Each participant will undergo testing at sea level and altitude after inhalation of iloprost and placebo, sequence is randomly assigned.

Primary Outcome Measures

Name	Time	Method
Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation	6 months

Secondary Outcome Measures

Name	Time	Method
Heart rate, tissue Doppler echocardiographic measurements	6 months

Trial Locations

Locations (1)

Loma Linda University; 🇺🇸 Loma Linda, California, United States