Trial record 6 of 15 for:    "Pulmonary edema of mountaineers"

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

This study has been completed.
Sponsor:
Collaborator:
University of Edinburgh
Information provided by:
Altitude Physiology Expeditions
ClinicalTrials.gov Identifier:
NCT00627965
First received: February 24, 2008
Last updated: NA
Last verified: February 2008
History: No changes posted
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness

Resource links provided by NLM:


Further study details as provided by Altitude Physiology Expeditions:

Primary Outcome Measures:
  • Pulmonary Artery Systolic Pressure (PASP)

Enrollment: 62
Study Start Date: March 2003
Study Completion Date: February 2008
Arms Assigned Interventions
Experimental: 1
Sildenafil citrate
Drug: Sildenafil citrate
50mg tds
Placebo Comparator: 2
Placebo
Drug: Placebo
Placebo tds

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant in Apex 2 high altitude expedition

Exclusion Criteria:

  • Previous history of high altitude pulmonary edema
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627965

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

Additional Information:
No publications provided by Altitude Physiology Expeditions

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Director, Altitude Physiology Expeditions
ClinicalTrials.gov Identifier: NCT00627965     History of Changes
Other Study ID Numbers: Sildenafil1
Study First Received: February 24, 2008
Last Updated: February 24, 2008
Health Authority: Scotland: Scottish Executive Health Department

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

Additional relevant MeSH terms:
Altitude Sickness
Edema
Pulmonary Edema
Hypertension, Pulmonary
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Lung Diseases
Citric Acid
Sildenafil
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Cardiovascular Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014