Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness

NCT ID: NCT00664001

Last Updated: 2008-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-03-31

Study Completion Date

2003-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Mountain Sickness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Control

Placebo tablet

Group Type PLACEBO_COMPARATOR

Matched placebo for anti-oxidant supplementation

Intervention Type DIETARY_SUPPLEMENT

Matched placebo for anti-oxidant supplementation

Intervention

Anti-oxidant supplementation

Group Type ACTIVE_COMPARATOR

Anti-oxidant supplementation

Intervention Type DIETARY_SUPPLEMENT

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.

Interventions

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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.

Intervention Type DIETARY_SUPPLEMENT

Matched placebo for anti-oxidant supplementation

Matched placebo for anti-oxidant supplementation

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Participants in Apex 2 trial

Exclusion Criteria

* High altitude pulmonary oedema (HAPE)
* Gasto-intestinal illness
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Edinburgh

OTHER

Sponsor Role collaborator

Altitude Physiology Expeditions

OTHER

Sponsor Role lead

Responsible Party

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Apex

Principal Investigators

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Kenneth Baillie

Role: PRINCIPAL_INVESTIGATOR

Apex Bioscience

Locations

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University of Edinburgh

Edinburgh, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Hall DP, MacCormick IJ, Phythian-Adams AT, Rzechorzek NM, Hope-Jones D, Cosens S, Jackson S, Bates MG, Collier DJ, Hume DA, Freeman T, Thompson AA, Baillie JK. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness. PLoS One. 2014 Jan 22;9(1):e81229. doi: 10.1371/journal.pone.0081229. eCollection 2014.

Reference Type DERIVED
PMID: 24465370 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23270443 (View on PubMed)

Baillie JK, Thompson AA, Irving JB, Bates MG, Sutherland AI, Macnee W, Maxwell SR, Webb DJ. Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial. QJM. 2009 May;102(5):341-8. doi: 10.1093/qjmed/hcp026. Epub 2009 Mar 9.

Reference Type DERIVED
PMID: 19273551 (View on PubMed)

Related Links

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Other Identifiers

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Anti-oxidant

Identifier Type: -

Identifier Source: org_study_id