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

Primary Purpose

High Altitude Pulmonary Edema, Acute Mountain Sickness

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sildenafil citrate
Placebo
Sponsored by
Altitude Physiology Expeditions
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for High Altitude Pulmonary Edema focused on measuring Sildenafil citrate, Prevention, High Altitude Pulmonary Edema, Acute Mountain Sickness, Healthy Lowland Subjects, Pulmonary Artery Systolic Pressure

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Participant in Apex 2 high altitude expedition

Exclusion Criteria:

  • Previous history of high altitude pulmonary edema

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    1

    2

    Arm Description

    Sildenafil citrate

    Placebo

    Outcomes

    Primary Outcome Measures

    Pulmonary Artery Systolic Pressure (PASP)

    Secondary Outcome Measures

    Full Information

    First Posted
    February 24, 2008
    Last Updated
    February 24, 2008
    Sponsor
    Altitude Physiology Expeditions
    Collaborators
    University of Edinburgh
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00627965
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2008
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2003 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    February 2008 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Altitude Physiology Expeditions
    Collaborators
    University of Edinburgh

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    High Altitude Pulmonary Edema, Acute Mountain Sickness
    Keywords
    Sildenafil citrate, Prevention, High Altitude Pulmonary Edema, Acute Mountain Sickness, Healthy Lowland Subjects, Pulmonary Artery Systolic Pressure

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    62 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1
    Arm Type
    Experimental
    Arm Description
    Sildenafil citrate
    Arm Title
    2
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Sildenafil citrate
    Intervention Description
    50mg tds
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo tds
    Primary Outcome Measure Information:
    Title
    Pulmonary Artery Systolic Pressure (PASP)

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Participant in Apex 2 high altitude expedition Exclusion Criteria: Previous history of high altitude pulmonary edema
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Matthew Bates
    Organizational Affiliation
    Altitude Physiology Expeditions
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    23270443
    Citation
    MacCormick IJ, Somner J, Morris DS, MacGillivray TJ, Bourne RR, Huang SS, MacCormick A, Aspinall PA, Baillie JK, Thompson AA, Dhillon B. Retinal vessel tortuosity in response to hypobaric hypoxia. High Alt Med Biol. 2012 Dec;13(4):263-8. doi: 10.1089/ham.2011.1097.
    Results Reference
    derived
    PubMed Identifier
    21962063
    Citation
    Bates MG, Thompson AA, Baillie JK, Sutherland AI, Irving JB, Hirani N, Webb DJ. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial. High Alt Med Biol. 2011 Fall;12(3):207-14. doi: 10.1089/ham.2011.0007.
    Results Reference
    derived
    Links:
    URL
    http://altitude.org
    Description
    Research group website coordinating future studies

    Learn more about this trial

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

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