Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness

Acute Mountain Sickness Clinical Trial

Official title:

Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00627965
• Other study ID #: Sildenafil1
• Status: Completed
• Phase: Phase 4
• First received: February 24, 2008
• Last updated: February 24, 2008
• Start date: March 2003
• Est. completion date: February 2008

Study information

• Verified date: February 2008
• Source: Altitude Physiology Expeditions
• Contact: n/a
• Is FDA regulated: No
• Health authority: Scotland: Scottish Executive Health Department
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether regular oral use of sildenafil citrate can prevent or attenuate high altitude illnesses.

Description:

High altitude pulmonary oedema (HAPE) is a life-threatening non-cardiogenic lung injury precipitated by exaggerated pulmonary hypertension. The incidence of this rapidly progressive illness, among the estimated 40 million visitors to high altitude each year, may be as high as 0.5-2.0%. The pathogenesis of HAPE is multifactorial and may include impaired clearance of alveolar fluid, increased pulmonary vascular permeability and genetic susceptibility. Elevated pulmonary artery pressure (PAP) caused by hypoxic pulmonary vasoconstriction (HPV) is a key prerequisite for the development of HAPE and thus the reduction of PAP is paramount in the prophylaxis and treatment of this devastating illness.

Nitric oxide (NO) is thought to play an important role in the exaggerated HPV that characterises HAPE. NO, constitutively produced in the lung by the enzyme endothelial nitric oxide synthase (eNOS), increases intracellular cGMP in pulmonary vascular smooth muscle and activates cGMP-dependent protein kinase, ultimately leading to a reduction in intracellular calcium and smooth muscle relaxation. HAPE-susceptible individuals exhale less NO during both normobaric and hypobaric hypoxia suggesting that a deficiency of NO synthesis may predispose to HAPE. At high altitude, inhaled NO causes a significantly greater reduction in the systolic PAP of HAPE-susceptible individuals compared to its effect on the PAP of HAPE-resistant subjects, but the administration of NO would be impractical in the field. Most recently, work has concentrated on another target in the NO pathway.

Sildenafil citrate is an orally active, potent and selective phosphodiesterase type-5 (PDE-5) inhibitor. PDE-5 is the predominant enzyme responsible for degradation of cGMP in the lung. In a small sea level study, Zhao et al. demonstrated that pre-treatment with sildenafil nearly completely abolished the pulmonary vasopressor response to breathing hypoxic gas in healthy humans. More recently, studies at altitude have also shown reductions in pulmonary artery systolic pressure (PASP) in subjects taking sildenafil at high altitude.

One potential problem with the use of sildenafil at altitude is that PDE-5 inhibitors may worsen symptoms of acute mountain sickness (AMS). Headache is a defining symptom in AMS and is a prominent side effect of sildenafil.

We conducted a double-blind placebo-controlled randomised trial to assess the effect of regular sildenafil administration on PASP and Lake Louise AMS score at an altitude of 5200 m.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: February 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Participant in Apex 2 high altitude expedition

Exclusion Criteria:

• Previous history of high altitude pulmonary edema

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Mountain Sickness
• Altitude Sickness
• High Altitude Pulmonary Edema
• Hypertension, Pulmonary
• Pulmonary Edema

Intervention

Drug:
• Sildenafil citrate
50mg tds
• Placebo
Placebo tds

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Altitude Physiology Expeditions	University of Edinburgh

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Artery Systolic Pressure (PASP)