Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction at Altitude

Sponsor

Loma Linda University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00724321

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypoxic Pulmonary Vasoconstriction	Drug: iloprost	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction With Exercise at High Altitude

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Nov 1, 2008

Actual Study Completion Date :

Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: Iloprost and placebo Each participant will undergo testing at sea level and altitude after inhalation of iloprost and placebo, sequence is randomly assigned.	Drug: iloprost A dose of inhaled iloprost (or placebo) will be given once at baseline and then at altitude. Measurements will be obtained before and after inhalation. Patients will then cross over and be given a dose of placebo (or iloprost)and measurements will be repeated.

Arm

Intervention/Treatment

Other: Iloprost and placebo

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

Drug: iloprost

A dose of inhaled iloprost (or placebo) will be given once at baseline and then at altitude. Measurements will be obtained before and after inhalation. Patients will then cross over and be given a dose of placebo (or iloprost)and measurements will be repeated.

Outcome Measures

Primary Outcome Measures

Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation [6 months]

Secondary Outcome Measures

Heart rate, tissue Doppler echocardiographic measurements [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

Known liver disease
Pregnancy
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