PLHARE: Pik Lenin High Altitude Research Expedition 2009

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Completed

CT.gov ID

NCT01571687

Collaborator

Kantonsspital Aarau (Other), Lotteriefonds des Kantons Aarau (Other), Schweizer Gesellschaft für Gebirgsmedizin (Other), University of Bern (Other)

Enrollment

Location

Arms

Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Oxidative Stress Cell-derived Microparticles	Dietary Supplement: antioxidant supplements Dietary Supplement: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Aug 1, 2009

Actual Study Completion Date :

Aug 1, 2009

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change from baseline in oxidative stress [during expedition, up to 22 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center of Laboratory Medicine Cantonal Hospital Aarau and University of Bern	Aarau		Switzerland	5001

Sponsors and Collaborators

University Hospital Inselspital, Berne
Kantonsspital Aarau
Lotteriefonds des Kantons Aarau
Schweizer Gesellschaft für Gebirgsmedizin
University of Bern

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