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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00627965
Recruitment Status : Completed
First Posted : March 4, 2008
Last Update Posted : March 4, 2008
University of Edinburgh
Information provided by:
Altitude Physiology Expeditions

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

Condition or disease Intervention/treatment Phase
High Altitude Pulmonary Edema Acute Mountain Sickness Drug: Sildenafil citrate Drug: Placebo Phase 4

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
Study Start Date : March 2003
Actual Study Completion Date : February 2008

Arm Intervention/treatment
Experimental: 1
Sildenafil citrate
Drug: Sildenafil citrate
50mg tds

Placebo Comparator: 2
Drug: Placebo
Placebo tds

Primary Outcome Measures :
  1. Pulmonary Artery Systolic Pressure (PASP)

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Participant in Apex 2 high altitude expedition

Exclusion Criteria:

  • Previous history of high altitude pulmonary edema

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00627965

Sponsors and Collaborators
Altitude Physiology Expeditions
University of Edinburgh
Principal Investigator: Matthew Bates Altitude Physiology Expeditions

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Director, Altitude Physiology Expeditions Identifier: NCT00627965     History of Changes
Other Study ID Numbers: Sildenafil1
First Posted: March 4, 2008    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: February 2008

Keywords provided by Altitude Physiology Expeditions:
Sildenafil citrate
High Altitude Pulmonary Edema
Acute Mountain Sickness
Healthy Lowland Subjects
Pulmonary Artery Systolic Pressure

Additional relevant MeSH terms:
Pulmonary Edema
Altitude Sickness
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Citric Acid
Sildenafil Citrate
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents