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
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
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
NCT ID
NCT00627965
First Posted
February 24, 2008
Last Updated
February 24, 2008
Sponsor
Altitude Physiology Expeditions
Collaborators
University of Edinburgh
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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