Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness

Acute Mountain Sickness Clinical Trial

Official title:

Randomized Double-Blind Placebo-Controlled Trial of Oral Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00664001
• Other study ID #: Anti-oxidant
• Status: Completed
• Phase: Phase 3
• First received: April 7, 2008
• Last updated: April 21, 2008
• Start date: March 2003
• Est. completion date: December 2003

Study information

• Verified date: April 2008
• Source: Altitude Physiology Expeditions
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: December 2003
• Est. primary completion date: August 2003
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participants in Apex 2 trial

Exclusion Criteria:

• High altitude pulmonary oedema (HAPE)

• Gasto-intestinal illness

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Mountain Sickness
• Altitude Sickness

Intervention

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.
• Matched placebo for anti-oxidant supplementation
Matched placebo for anti-oxidant supplementation

Locations

Country	Name	City	State
United Kingdom	University of Edinburgh	Edinburgh

Sponsors (2)

Lead Sponsor	Collaborator
Altitude Physiology Expeditions	University of Edinburgh

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Mountain Sickness (AMS) as assessed by Lake Louise Consensus symptom score		Day 2	No
Secondary	Pulmonary artery systolic pressure		Day 6	No