Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness

This study has been completed.
Sponsor:
Collaborator:
University of Edinburgh
Information provided by:
Altitude Physiology Expeditions
ClinicalTrials.gov Identifier:
NCT00664001
First received: April 7, 2008
Last updated: April 21, 2008
Last verified: April 2008
  Purpose

Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) are complications of rapid ascent to high altitude. Several features suggest that raised intracranial pressure (ICP) may be an important factor in the pathogenesis of AMS. Magnetic resonance imaging of HACE patients has demonstrated that the oedema in HACE is of the vasogenic, rather that cytotoxic, type. Thus it is likely that cerebrovascular permeability has an important role in the development of AMS and HACE.

Reactive oxygen species (ROS) have been shown to alter the permeability of the blood-brain barrier in severe ischaemia, causing vasogenic cerebral oedema. Endogenous antioxidant systems may have some capacity to respond to oxidative stress in hypoxia. The plasma concentration of urate, a powerful endogenous antioxidant, rises on acute exposure to high altitude and may play a crucial antioxidant role in systemic hypoxia. This antioxidant prevents free-radical induced cerebral oedema in animal models.

There are numerous sources of ROS in hypoxia, including the mitochondrial electron transfer chain, haemoglobin (Hb) autoxidation and xanthine oxidase activity. There have been several reports of raised markers of oxidative stress in humans at moderate altitude (<3000m).

Oral antioxidant supplementation with preparations containing vitamins C and E in humans at altitude has been shown to decrease breath pentanes (a marker of oxidative stress), and improve erythrocyte filterability. In a small randomised controlled trial, Bailey and Davies demonstrated a significant reduction in symptoms of AMS in subjects taking an oral antioxidant cocktail.

The antioxidants alpha-lipoic acid, vitamin C and vitamin E act synergistically to provide membrane protection from free radical damage, and may protect against hypoxia-induced vascular leakage. We hypothesised that this combination of antioxidants would reduce the severity of acute mountain sickness, and reduce pulmonary artery pressures, in healthy lowlanders acutely exposed to high altitude.


Condition Intervention Phase
Acute Mountain Sickness
Dietary Supplement: Anti-oxidant supplementation
Dietary Supplement: Matched placebo for anti-oxidant supplementation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Double-Blind Placebo-Controlled Trial of Oral Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness.

Resource links provided by NLM:


Further study details as provided by Altitude Physiology Expeditions:

Primary Outcome Measures:
  • Acute Mountain Sickness (AMS) as assessed by Lake Louise Consensus symptom score [ Time Frame: Day 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pulmonary artery systolic pressure [ Time Frame: Day 6 ] [ Designated as safety issue: No ]

Enrollment: 83
Study Start Date: March 2003
Study Completion Date: December 2003
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Placebo tablet
Dietary Supplement: Matched placebo for anti-oxidant supplementation
Matched placebo for anti-oxidant supplementation
Active Comparator: Intervention
Anti-oxidant supplementation
Dietary Supplement: Anti-oxidant supplementation
Daily dose of 1g L-ascorbic acid, 400 IU of alpha-tocopherol acetate, and 600mg of alpha-lipoic acid in sealed capsules as anti-oxidant supplementation.

Detailed Description:

Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) are complications of rapid ascent to high altitude. By definition, AMS is a benign condition, but it is likely that the same pathology underlies high altitude cerebral oedema (HACE). In contrast, HAPE occurs in the context of pathologically elevated pulmonary artery pressures and uneven distribution of hypoxic pulmonary vasoconstriction across the pulmonary vascular bed.

Several features suggest that raised intracranial pressure (ICP) may be an important factor in the pathogenesis of AMS. Magnetic resonance imaging of HACE patients has demonstrated that the oedema in HACE is of the vasogenic, rather that cytotoxic, type. Thus it is likely that cerebrovascular permeability has an important role in the development of AMS and HACE.

Reactive oxygen species (ROS) have been shown to alter the permeability of the blood-brain barrier in severe ischaemia, causing vasogenic cerebral oedema. Endogenous antioxidant systems may have some capacity to respond to oxidative stress in hypoxia. The plasma concentration of urate, a powerful endogenous antioxidant, rises on acute exposure to high altitude and may play a crucial antioxidant role in systemic hypoxia. This antioxidant prevents free-radical induced cerebral oedema in animal models.

The pathogenesis of HAPE is understood to have two components: (i) increased pulmonary arterial pressures secondary to hypoxic pulmonary vasoconstriction and; (ii) an increase in endothelial permeability, possibly due to stress rupture of pulmonary capillaries. There is much debate surrounding the cellular mechanisms of hypoxic pulmonary vasoconstriction, but it is likely that ROS have an important role.

There are numerous sources of ROS in hypoxia, including the mitochondrial electron transfer chain, haemoglobin (Hb) autoxidation and xanthine oxidase activity. There have been several reports of raised markers of oxidative stress in humans at moderate altitude (<3000m).

Oral antioxidant supplementation with preparations containing vitamins C and E in humans at altitude has been shown to decrease breath pentanes (a marker of oxidative stress), and improve erythrocyte filterability. In a small randomised controlled trial, Bailey and Davies demonstrated a significant reduction in symptoms of AMS in subjects taking an oral antioxidant cocktail.

The antioxidants alpha-lipoic acid, vitamin C and vitamin E act synergistically to provide membrane protection from free radical damage, and may protect against hypoxia-induced vascular leakage. We hypothesised that this combination of antioxidants would reduce the severity of acute mountain sickness, and reduce pulmonary artery pressures, in healthy lowlanders acutely exposed to high altitude.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants in Apex 2 trial

Exclusion Criteria:

  • High altitude pulmonary oedema (HAPE)
  • Gasto-intestinal illness
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00664001

Locations
United Kingdom
University of Edinburgh
Edinburgh, United Kingdom
Sponsors and Collaborators
Altitude Physiology Expeditions
University of Edinburgh
Investigators
Principal Investigator: Kenneth Baillie Apex Bioscience
  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: JK Baillie, Apex
ClinicalTrials.gov Identifier: NCT00664001     History of Changes
Other Study ID Numbers: Anti-oxidant
Study First Received: April 7, 2008
Last Updated: April 21, 2008
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Altitude Sickness
Respiration Disorders
Respiratory Tract Diseases
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014