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

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Brief Title

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

Official Title

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

Brief Summary

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

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 Phase

Phase 4

Study Type

Interventional


Primary Outcome

Pulmonary Artery Systolic Pressure (PASP)


Condition

High Altitude Pulmonary Edema

Intervention

Sildenafil citrate

Study Arms / Comparison Groups

 1
Description:  Sildenafil citrate

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

62

Start Date

March 2003

Completion Date

February 2008


Eligibility Criteria

        Inclusion Criteria:

          -  Participant in Apex 2 high altitude expedition

        Exclusion Criteria:

          -  Previous history of high altitude pulmonary edema
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Matthew Bates, , 



Administrative Informations


NCT ID

NCT00627965

Organization ID

Sildenafil1



Study Sponsor

Altitude Physiology Expeditions

Collaborators

 University of Edinburgh

Study Sponsor

Matthew Bates, Principal Investigator, Altitude Physiology Expeditions


Verification Date

February 2008