Pik Lenin High Altitude Research Expedition 2009 (PLHARE)

Pik Lenin High Altitude Research Expedition 2009, a Follow-up Project of the Muztagh Ata High Altitude Research Expedition 2005

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.

Study Overview

• Status: Completed
• Conditions: Oxidative Stress; Cell-derived Microparticles
• Intervention / Treatment: Dietary supplement: antioxidant supplements; Dietary supplement: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Center of Laboratory Medicine Cantonal Hospital Aarau and University of Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• good health status
• age 18-65
• mountaineering experience

Exclusion Criteria:

• any metabolic disorders
• regular drug intake
• any disease of the lungs
• any disease of the heart
• any renal abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: antioxidant supplements; 800 I.E. Vitamin E, 1000mg Vitamin C, 200000 I.E. Vitamin A, 600mg Acetylcystein.	Dietary supplement: antioxidant supplements; Intake of 6 tablets daily containing: 800 I.E. Vitamin E, 1000mg Vitamin C, 200000 I.E. Vitamin A, 600mg Acetylcystein.
Placebo Comparator: Placebo; identically appearing placebo	Dietary supplement: Placebo; Intake of 6 identically appearing tablets daily containing placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in oxidative stress	during expedition, up to 22 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in coagulation activation	during expedition, up to 22 days
Change from baseline in acute mountain sickness score	during expedition, up to 22 days
Change from baseline in oxygen saturation in blood	during expedition, up to 22 days

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Kantonsspital Aarau; University of Bern; Lotteriefonds des Kantons Aarau; Schweizer Gesellschaft für Gebirgsmedizin
• Investigators: Study Chair: Andreas R Huber, Prof. Dr. med., Center of Laboratory Medicine Cantonal Hospital Aarau and University of Bern; Principal Investigator: Jacqueline Pichler Hefti, Dr. med., Division of Pneumology, Inselspital Bern, Universityhospital Bern

Publications and helpful links

General Publications

• Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet. 1976 Nov 27;2(7996):1149-55. doi: 10.1016/s0140-6736(76)91677-9.
• Basnyat B, Murdoch DR. High-altitude illness. Lancet. 2003 Jun 7;361(9373):1967-74. doi: 10.1016/S0140-6736(03)13591-X.
• Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003 Dec;42(6):1075-81. doi: 10.1161/01.HYP.0000100443.09293.4F. Epub 2003 Oct 27.
• Huet O, Dupic L, Harrois A, Duranteau J. Oxidative stress and endothelial dysfunction during sepsis. Front Biosci (Landmark Ed). 2011 Jan 1;16(5):1986-95. doi: 10.2741/3835.
• Pichler Hefti J, Risch L, Hefti U, Scharrer I, Risch G, Merz TM, Turk A, Bosch MM, Barthelmess D, Schoch O, Maggiorini M, Huber AR. Changes of coagulation parameters during high altitude expedition. Swiss Med Wkly. 2010 Feb 20;140(7-8):111-7. doi: 10.4414/smw.2010.12910.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: April 3, 2012
• First Posted (Estimate): April 5, 2012

Study Record Updates

• Last Update Posted (Estimate): April 5, 2012
• Last Update Submitted That Met QC Criteria: April 3, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: oxidative stress; hypoxia; vitamins; N-Acetylcystein; blood coagulation disorders; cell-derived microparticles; expedition
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants
• Other Study ID Numbers: 2008/071; 07.09.34 (Other Identifier: University Hospital Berne)