Pik Lenin High Altitude Research Expedition 2009
Condition: Oxidative Stress; Cell-derived Microparticles
Study type: Interventional

Summary: 
      Exposure to hypobaric hypoxia demands maximum effort of the body and can lead to high
      altitude illnesses. Recently, there is rising interest on coagulation activation during
      trekking and mountaineering in higher regions and on development of oxidative stress due to
      hypoxia. 30 volunteers have been examined during an high altitude research expedition to the
      7134m high mount Pik Lenin in Kyrgyzstan to investigate mechanisms of coagulation activation
      and effects of antioxidant supplements on oxidative stress.
    

Detailed description: 
      Reactions to acute exposure to high altitude and the process of acclimatization has been of
      scientific interest since many years. High altitude illnesses are specified by three
      different entities: acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and
      high altitude cerebral edema (HACE). Prevalence of AMS is known to be between 10 to 20% for
      altitudes between 4000 and 5000m, increasing significantly in higher altitude. The prevalence
      depends on the ascent rate, individual susceptibility and physical exhaustion.

      Although mechanisms leading to high altitude illnesses are not yet completely clear some
      progress has been made. It is well accepted that excessive pulmonary hypertension may lead to
      HAPE. Furthermore, there is rising evidence about endothelial dysfunction being involved in
      disease progression. Some cellular and molecular mechanisms of acute (hypobaric) hypoxia,
      possibly leading to endothelial dysfunction, have been studied in a few experimental and
      field settings. Paradoxical increase in systemic oxidative stress is seen under hypoxic
      conditions, such as high altitude stay. Reactive oxygen species (ROS) could be demonstrated
      in many endothelial disorders and capillary leakage syndromes such as septicaemia, myocardial
      infarct and stroke. Furthermore, coagulation activation might result from endothelial
      dysfunction but also amplify endothelial interruption. Still, most of our knowledge
      concerning effects of hypoxia in general but also concerning oxidative stress is from in
      vitro studies (e.g. cancer cells).

      In the context of a high altitude expedition human subjects can safely be submitted to
      prolonged hypoxia to explore generation of ROS and extent of procoagulatory state.

      Objective

      The purpose of our study is to confirm excessive oxidative stress found in our previous study
      in 2005 and to investigate whether oxidative stress during high altitude exposure can be
      modified by dietary supplementations of specific antioxidants. Moreover, we like to study
      mechanisms of coagulation activation by assessing extent of thrombocytic and endothelial
      microparticles.

      Methods

      After approval of the study by the regional ethics committee, written informed consent has
      been obtained from 30 healthy volunteers (low land residents with mountaineering experience,
      age 18-65 years). After baseline testing, double-blind randomization into 2 groups of 15
      persons took place. One group received oral medication with vitamin E, vitamin C, vitamin A
      and acetylcystein daily, while the other group was provided with an identical appearing
      placebo preparation. Substitution started 2 month before the expedition. After examination at
      "ground 0" in Zurich (409m) all members underwent testing in Base Camp (3550m), twice in
      advanced Base Camp (4550m), in Camp 1 (5430m), and in Camp 2 (6265m). Beside blood sampling,
      clinical examinations were performed. Metabolomics, a mass-spectrometry based analysis, for
      measurement of oxidative stress, will be performed. In a subgroup microparticles will be
      detected by annexin V based ELISA and by flow cytometry using specific antibodies.
    

Intervention name(s): antioxidant supplements; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Intake of 6 tablets daily containing: 800 I.E. Vitamin E, 1000mg Vitamin C, 200000 I.E. Vitamin A, 600mg Acetylcystein.; Intake of 6 identically appearing tablets daily containing placebo
Intervention MeSH terms: Antioxidants
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: expedition; hypoxia; blood coagulation disorders; cell-derived microparticles; oxidative stress; N-Acetylcystein; vitamins