Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness

NCT00664001 | Completed Phase 3

• 1 other identifier: Anti-oxidant
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Mountain Sickness

Outcome Measures

Primary Outcomes (1)

• Acute Mountain Sickness (AMS) as assessed by Lake Louise Consensus symptom score

  Day 2

Secondary Outcomes (1)

• Pulmonary artery systolic pressure

  Day 6

Study Arms (2)

Control

PLACEBO COMPARATOR

Placebo tablet

Dietary Supplement: Matched placebo for anti-oxidant supplementation

Intervention

ACTIVE COMPARATOR

Anti-oxidant supplementation

Dietary Supplement: Anti-oxidant supplementation

Interventions

Anti-oxidant supplementation 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.

Intervention

Matched placebo for anti-oxidant supplementation DIETARY_SUPPLEMENT

Matched placebo for anti-oxidant supplementation

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants in Apex 2 trial

You may not qualify if:

• High altitude pulmonary oedema (HAPE)
• Gasto-intestinal illness

Sponsors & Collaborators

• Altitude Physiology Expeditions: lead
• University of Edinburgh: collaborator

Study Sites (1)

University of Edinburgh

Edinburgh, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 24465370 DERIVED

• 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.

  PMID: 23270443 DERIVED

• 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.

  PMID: 19273551 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Altitude Sickness

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Kenneth Baillie

  Apex Bioscience

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 7, 2008
• First Posted: April 22, 2008
• Study Start: March 1, 2003
• Primary Completion: August 1, 2003
• Study Completion: December 1, 2003
• Last Updated: April 22, 2008

Record last verified: 2008-04

Locations

GB (1)