Official Title: “Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness”

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

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Sildenafil citrate
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Pulmonary Artery Systolic Pressure (PASP)

Inclusion Criteria:

• Participant in Apex 2 high altitude expedition

Exclusion Criteria:

• Previous history of high altitude pulmonary edema

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Altitude Physiology Expeditions

Overall Clinical Trial Officials and Contacts

Matthew Bates Principal Investigator Altitude Physiology Expeditions  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00627965

Study ID Number: Sildenafil1

ClinicalTrials.gov Identifier: NCT00627965

Health Authority: Scotland: Scottish Executive Health Department

Research group website coordinating future studies