The Pre-acclimatization Augmented Extreme Altitude Expedition

Study Overview
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Brief Summary
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The aim of this study is to investigate the effect of pre-acclimatization in a nitrogen tent at home, ventilated with a slightly increased nitrogen percentage, in preparation for an expedition at extreme altitude. Specifically, the current study aims to gather knowledge, whether pre-acclimatization, first, leads to improved capillary function during an expedition to extreme altitude, and second, affects incidence of altitude sickness and the likelihood of reaching the expedition destination without oxygen supplementation. The project will be carried out in two phases corresponding to two randomized controlled trials in healthy volunteers, who are participating in an expedition at extreme altitudes with or without pre-acclimatization.

Detailed Description
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Expeditions to the world's highest peaks are attempted by increasing numbers of alpinists, taking advantage of broad commercial support. At extreme altitude successful functioning, and even survival, are only possible with adequate acclimatization, which consists of time-consuming exposure to gradually higher sleeping altitudes. Generally, an increase in 300-600 m per day at altitudes above 3000 m, and the minimization of cumulative time spend above 6500 m, are considered safe practice. Mainly in an attempt to accelerate expeditions to extreme altitudes, a preacclimatization technique using nitrogen concentration tent induced normobaric hypoxia is increasingly employed in practice, and already part commercial expedition plans. Some previous research indicates that intermittent normobaric hypoxia may reduce the incidence of acute mountain sickness, while the results from other studies remain inconclusive or negative. One study has not found serious adverse effects related to intermittent normobaric hypoxia, such as high-altitude pulmonary or cerebral edema. Thus, despite the emergence of increasing numbers of commercial expedition programs making use of nitrogen concentration tent preacclimatization protocols, many factors remain unclear. Next to remaining uncertainties regarding the extent of the hypoxic condition induced by these devices, current data does not allow adequate conclusions regarding the choice of optimal preacclimatization protocol, optimal associated ascent profiles, and possible effects on oxygen delivery capacity to the tissue, incidence of high-altitude related disease, and even summit success. Thus, the present study aims to conduct a randomized controlled trial to assess the efficacy of nitrogen concentration tent preacclimatization as part of two expeditions to extreme altitude. The immediate effects of nitrogen concentration tent preacclimatization are assessed through continuous monitoring of oxygen partial pressure in the tent and the hemoglobin oxygen saturation throughout preacclimatization. To test whether preacclimatization is associated with physiologic adaptation, tissue red blood cell perfusion as a main contributor to increase oxygen delivery capacity in the microcirculation throughout acclimatization to extreme altitude, is assessed using non-invasive handheld vital microscopy during preacclimatization and throughout the expedition, and the incidence and severity of high-altitude related disease and summit success, are recorded during the expeditions.

Official Title
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The PRe-Acclimatization auGmented extreMe Altitude eXpedition (PRAGMAX) Randomized Controlled Trial

Conditions
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Altitude Hypoxia, Perfusion; Complications

Intervention / Treatment
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* Other: Nitrogen tent preacclimatization to high altitude


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Active alpinists (active alpinists denotes individuals with regular experience in alpine high mountain climbing in rock, ice and snow terrain of difficulty WS - ZS according to the Swiss Alpine Club (SAC-CAS) grading scale assessed in a self-reporting questionnaire age > 18 years Exclusion Criteria: history of high-altitude pulmonary edema or cerebral edema pregnancy or lactation heart failure (AHA Stage B and above) pulmonary hypertension pulmonary disease excluding mild bronchial asthma chronic kidney failure (KDIGO Stage 1 and above) chronic liver disease subjects with a history of smoking (> 5 PY), and high familiar predisposition for cardiovascular disease, when combined with smoking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two independent randomized-controlled trials with each an intervention and a control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preacclimatization group<br>The participants assigned to the preacclimatization group will undergo a defined preacclimatization program by sleeping in a nitrogen concentration tent prior to an expedition to high altitude. | Other: Nitrogen tent preacclimatization to high altitude<br>* The participants assigned to the preacclimatization group spend a minimum of six hours during sleep, throughout the acclimatization period (four weeks preceding the expedition) in a nitrogen concentration tent (Hypoxico OHG, Traunstein, Germany) set to an environmental PO2 corresponding to an altitude of 2500 masl, with a progression to 5500 masl within 28 days in steps of 1000 m every seven days. Respiratory Polygraphy is used to detect periodic breathing, SpO2, and heart rate continuously during sleep and is performed before and after the designated preacclimatization period, and repetitively when increasing normobaric hypoxia in the group with nitrogen concentration tent preacclimatization.<br>|
| No Intervention: Control group<br>The participants assigned to the control group sleep in their regular environment without use of a nitrogen concentration tent prior to an expedition to a high altitude expedition. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in sublingual total capillary vessel density (TVD) induced by preacclimatization and high-altitude exposure (change from baseline) | Sublingual microcirculatory functional hemodynamic variable measured using a handheld vital microscopy. (ref: Communications Biology 2019; 2: 217 UND ref. Curr Opin Crit Care 2020; 26: 273-280.) | Microcirculation assessment taken: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepa | 
| Difference in sublingual functional capillary density (FCD) induced by preacclimatization and high-altitude exposure (change from baseline) | Sublingual microcirculatory functional hemodynamic variable measured using a handheld vital microscopy. (ref: Communications Biology 2019; 2: 217 UND ref. Curr Opin Crit Care 2020; 26: 273-280.) | Microcirculation assessment taken: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepa | 
| Difference in sublingual red blood cell velocity (RBCv) induced by preacclimatization and high-altitude exposure (change from baseline) | Sublingual microcirculatory functional hemodynamic variable measured using a handheld vital microscopy. (ref: Communications Biology 2019; 2: 217 UND ref. Curr Opin Crit Care 2020; 26: 273-280.) | Microcirculation assessment taken: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepa | 
| Difference in sublingual capillary hematocrits (cHct) induced by preacclimatization and high-altitude exposure (change from baseline) | Sublingual microcirculatory functional hemodynamic variable measured using a handheld vital microscopy. (ref: Communications Biology 2019; 2: 217 UND ref. Curr Opin Crit Care 2020; 26: 273-280.) | Microcirculation assessment taken: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepa | 
| Difference in sublingual Tissue red blood cell perfusion (tRBCp) induced by preacclimatization and high-altitude exposure (change from baseline) | Sublingual microcirculatory functional hemodynamic variable measured using a handheld vital microscopy. (ref: Communications Biology 2019; 2: 217 UND ref. Curr Opin Crit Care 2020; 26: 273-280.) | Microcirculation assessment taken: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepa | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in acute mountain sickness (Lake Louise score) | Efficacy of the nitrogen concentration tent for high altitude preacclimatization by means of incidence and severity of acute mountain sickness (LLS-AMS score) | LLS_AMS score reported: 4 and 1 week prior to the expedition start (preacclimatization), Day 5 to 10 of the expedition in Nepal, Day 2 after the return from Nepal | 
| Summit success | Efficacy of nitrogen concentration tent for high altiude preacclimatization by means of incidence and severity of summit success | Day 9 of the expedition in Nepal (Summit attempt) | 
| Nitrogen tent | Proportion of preacclimatization time in the nitrogen concentration tent within the target environmental oxygen partial pressure within a 5% boundary | 4 weeks (prior to the expedition start (preacclimatization)) | 
| Low hemoglobin oxygen saturation | Proportion of preacclimatization time with a hemoglobin oxygen saturation below 90% | 4 weeks (prior to the expedition start (preacclimatization)) | 
| Hemoglobin oxgen saturation dips | Occurrence of dips in hemoglobin oxygen saturation below 80% for >5 min during preacclimatization | 4 weeks (prior to the expedition start (preacclimatization)) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microcirculation, Oxygen delivery capacity, Preacclimatization, nitrogen concentration tent