The Psychophysiological Effect of Simulated and Terrestrial Altitude
Phase: NA
Conditions: Hypoxia, Altitude Hypoxia, Altitude Sickness, Altitude, Mountain Sickness, Hypoxia, Altitude
Sponsor: University of Applied Sciences and Arts of Southern Switzerland

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 1 from 61 
 
 
The Psychophysiological Effect of Terrestrial Altitude and 
Normobaric Hypoxia 
- a randomized clinical trial 
 
  Clinical Trial Protocol 
Short title 
 Effect of Terrestrial Altitude and Normobaric Hypoxia 
Study Type: 
Other clinical trial with a certified Category A device  
Study Categorisation: 
Another clinical trial Cat. pursuant to Art. 61 of the Ordinance 
Study Registration: 
- 
Study Identifier: 
-  
Sponsor:  
 
 
 
 
 
 
Investigator: 
University of Applied Sciences  
Department of Business Economics, Health and Social Care 
Physiotherapy Graubünden 
 Weststrasse 8 
 7302 Landquart 
 +41 81 300 01 70 
 
Contact / Director of Studies 
Dr. Clijsen Ron, PhD 
University of Applied Sciences and Arts Southern Switzerland  
Physiotherapy Graubünden  
Weststrasse 8, 7302 Landquart 
+41 81 300 01 75 
ron.clijsen@supsi.ch 
 
Investigational Product: 
Cloud 9  
Protocol Version and Date: 
Study protocol – Version 02 – 1.5.2019 
 
 
 
 
 
 
Originally in German, translated into English 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 2 from 61 
 
CONFIDENTIALITY 
The information in this protocol is confidential and the property of the University of Applied Sciences 
and Arts Southern Switzerland (SUPSI), Department of Business Economics, Health and Social 
Care, Physiotherapy Graubünden in Landquart, Switzerland. The content of this protocol should not be 
forwarded, reproduced, published or passed on to others – neither in full text version nor in parts thereof 
– without the written consent of the head of the institute. Exceptions to this are the statements in the 
subject information and the declaration of consent of the study participants. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 3 from 61 
 
SIGNATURE OF THE PERSON RESPONSIBLE FOR THE STUDY 
 
Study number 
- 
Study Title 
The Psychophysiological Effect of Terrestrial Altitude and 
Normobaric Hypoxia - A Randomized Clinical Trial 
 
Sponsor: 
I have reviewed this study protocol, version 02 of 01.05.2019, and confirm that the study complies with 
the World Medical Association Declaration of Helsinki, ICH-GCP Guidelines, the ISO 14155 standard 
(where applicable), as well as the locally applicable Swiss Ordinance on Clinical Trials KlinV.  
 
University of Applied Sciences Southern Switzerland, Department of Business Economics, Health and 
Social Care, Physiotherapy Graubünden  
 
Sponsor (Thim van der Laan AG) 
Thim van der Laan jr. 
 
 
Landquart, 01.05.2019  
 
 
Place/Date 
 
Signature 
 
 
 
Investigator: 
I have reviewed this study protocol, version 02 of 01.05.2019, and confirm that the study complies with 
the World Medical Association Declaration of Helsinki, ICH-GCP Guidelines, the ISO 14155 standard 
(where applicable), as well as the locally applicable Swiss Ordinance on Clinical Trials KlinV.  
 
University of Applied Sciences Southern Switzerland, Department of Business Economics, Health and 
Social Care, Physiotherapy Graubünden  
 
Investigator 
Dr. Ron Clijsen 
 
 
Landquart, 01.05.2019  
 
 
Place/Date 
 
Signature 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 4 from 61 
 
TABLE OF CONTENTS 
STUDY SCHEDULE ............................................................................................................................. 17 
1 
STUDIEN-ADMINISTRATION ....................................................................................................... 18 
1.1 
Sponsor ...................................................................................................................................... 18 
1.2 
Investigator ................................................................................................................................. 18 
1.3 
Examiner ..................................................................................................................................... 18 
1.4 
Statistician .................................................................................................................................. 19 
1.5 
Laboratory Manager (Investigator) ............................................................................................. 20 
1.6 
Monitoring of the study ............................................................................................................... 20 
1.7 
Privacy ........................................................................................................................................ 20 
1.8 
Other committees or institutes involved ...................................................................................... 20 
2 
ETHNIC & REGULATORY ASPECTS .......................................................................................... 21 
2.1 
Study Registration ...................................................................................................................... 21 
2.2 
Categorization of the study ......................................................................................................... 21 
2.3 
Competent Ethics Committee (CEC) .......................................................................................... 21 
2.4 
Competent Authorities (CA) ........................................................................................................ 21 
2.5 
Ethical Leadership of the Study .................................................................................................. 21 
2.6 
Conflict ........................................................................................................................................ 21 
2.7 
Patient information and informed consent .................................................................................. 22 
2.8 
Confidentiality & Privacy ............................................................................................................. 22 
2.9 
Early termination of the study ..................................................................................................... 22 
2.10 Adjustments to the protocol ........................................................................................................ 22 
3 
BACKGROUND AND RATIONALE .............................................................................................. 24 
3.1 
Background and justification ....................................................................................................... 24 
3.2 
Medical product and indication ................................................................................................... 24 
3.3 
Preclinical evidence .................................................................................................................... 25 
3.4 
Current clinical evidence ............................................................................................................. 26 
3.5 
Medical product: method of application in the study ................................................................... 26 
3.6 
Peers .......................................................................................................................................... 26 
3.7 
Risk / Benefits ............................................................................................................................. 26 
4 
STUDY OBJECTIVES ................................................................................................................... 28 
4.1 
General objectives ...................................................................................................................... 28 
4.2 
Primary objectives ...................................................................................................................... 28 
4.3 
Secondary Objectives ................................................................................................................. 28 
4.4 
Other safety aspects (long-term) ................................................................................................ 29 
5 
STUDENT OUTCOMES ................................................................................................................ 30 
5.1 
Primary outcomes ....................................................................................................................... 30 
5.2 
Secondary outcomes .................................................................................................................. 32 
5.3 
Security considerations ............................................................................................................... 32 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 5 from 61 
 
6 
STUDIENDESIGN ......................................................................................................................... 33 
6.1 
Method for minimizing influencing factors ................................................................................... 33 
6.1.1 Randomization .................................................................................................................... 33 
6.1.2 Blinding ............................................................................................................................... 33 
6.1.3 Other Methods .................................................................................................................... 33 
6.2 
Procedure for unblinding (code break) ....................................................................................... 33 
6.3 
Procedure for unblinding (code break) ....................................................................................... 33 
7 
STUDENT POPULATION ............................................................................................................. 35 
7.1 
Inclusion Criteria ......................................................................................................................... 35 
7.2 
Recruitment and Screening ........................................................................................................ 35 
7.3 
Allocation of situations ................................................................................................................ 36 
7.4 
Discontinuation of study participation ......................................................................................... 36 
8 
STUDY INTERVENTION ............................................................................................................... 37 
8.1 
Medical Device ID ....................................................................................................................... 37 
8.1.1 Intervention product ............................................................................................................ 37 
8.1.2 Control intervention ............................................................................................................ 37 
8.1.3 Packaging, labeling and use ............................................................................................... 37 
8.1.4 Storage ............................................................................................................................... 37 
8.2 
Administration of the experiment ................................................................................................ 37 
8.2.1 Experimental intervention ................................................................................................... 37 
8.2.2 Control intervention ............................................................................................................ 38 
8.3 
Dosage, application modification ................................................................................................ 38 
8.4 
Adherence to the study intervention ........................................................................................... 38 
8.5 
Follow-up treatment of eliminated participants ........................................................................... 38 
8.6 
Preventive measurements .......................................................................................................... 38 
8.7 
Accompaniments ........................................................................................................................ 38 
8.8 
Liability ........................................................................................................................................ 39 
8.9 
Return of the medical device ...................................................................................................... 39 
9 
STUDY STRUCTURE & EVALUATION ....................................................................................... 40 
9.1 
Schedule Study Protocol ............................................................................................................ 40 
9.1.1 Measurement of primary results ......................................................................................... 41 
9.1.2 Measurement of primary results ......................................................................................... 42 
9.1.3 Measurement of secondary results .................................................................................... 43 
9.1.4 Collection of further results ................................................................................................. 43 
9.1.5 Collection of safety parameters .......................................................................................... 43 
9.1.6 Collection of data in case of early termination of studies ................................................... 44 
9.2 
Procedure at each visit of the test subjects ................................................................................ 44 
9.2.1 Single measurement ........................................................................................................... 44 
9.2.2 Multiple visits ...................................................................................................................... 44 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 6 from 61 
 
10 SAFETY ........................................................................................................................................ 47 
10.1 Drug study .................................................................................................................................. 47 
10.1.1 Definition and assessment of (serious) adverse events and other safety related events ... 47 
10.1.2 Reporting of serious adverse events (SAE) and other safety related events ..................... 47 
10.1.3 Follow up of (Serious) Adverse Events .............................................................................. 47 
10.2 Medical Device Category C studies ............................................................................................ 47 
10.2.1 Definition and Assessment of (Serious) Adverse Events and other safety related events . 47 
10.2.2 Reporting of (Serious) Adverse Events and other safety related events ............................ 47 
10.2.3 Follow up of (Serious) Adverse Events .............................................................................. 47 
10.3 Medical Device Category A studies ............................................................................................ 47 
10.3.1 Definition and recording of safety-relevant events ............................................................. 47 
10.3.2 Reporting of Safety related events ..................................................................................... 48 
10.3.3 Notification of a security-relevant event .............................................................................. 48 
11 STATISTICAL METHODS ............................................................................................................ 49 
11.1 Hypotheses & Factors ................................................................................................................ 49 
11.2 Sample size ................................................................................................................................ 52 
11.3 Criteria for the statistical use of data in the case of incomplete data sets .................................. 52 
11.4 Scheduled analyses .................................................................................................................... 52 
11.4.1 Datasets and Data Population ............................................................................................ 52 
11.4.2 Primary Analysis ................................................................................................................. 53 
11.4.3 Secondary Analysis ............................................................................................................ 53 
11.4.4 Interim analyses ................................................................................................................. 53 
11.4.5 Security analyses ............................................................................................................... 53 
11.4.6 Deviations ........................................................................................................................... 53 
11.5 Drop-outs and missing data ........................................................................................................ 53 
12 QUALITY ASSURANCE AND CONTROL .................................................................................... 54 
12.1 Data Archiving ............................................................................................................................ 54 
12.1.1 Forms ................................................................................................................................. 54 
12.1.2 Specification of forms ......................................................................................................... 54 
12.1.3 Archiving of data ................................................................................................................. 54 
12.2 Data management ...................................................................................................................... 54 
12.2.1 Data Management System ................................................................................................. 54 
12.2.2 Data security and backup ................................................................................................... 54 
12.2.3 Analysis and archiving ........................................................................................................ 55 
12.2.4 Validation of electronic data ............................................................................................... 55 
12.3 Monitoring ................................................................................................................................... 55 
12.4 Audits and inspections ................................................................................................................ 55 
12.5 Confidentiality and data protection ............................................................................................. 55 
12.6 Retention of biological material and health-related data ............................................................. 56 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 7 from 61 
 
13 PUBLICATION AND DISCLOSURE OF DATA ............................................................................ 57 
14 FUNDING AND SUPPORT ........................................................................................................... 58 
14.1 
Financing ............................................................................................................................ 58 
15 INSURANCE ................................................................................................................................. 59 
16 REFERENCES .............................................................................................................................. 60 
17 APPENDIX .................................................................................................................................... 61 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 8 from 61 
 
Study Synopsis  
 
Sponsor / 
Sponsor-
Investigator 
Sponsor  
Thim van der Laan AG  
Thim van der Laan jr.  
Weststrasse 8 / CH-7302 Landquart  
 
Investigator 
University of Applied Sciences  
Department of Business Economics, Health and Social Care 
Physiotherapy Graubünden  
Attn: Dr. Ron Clijsen 
Weststrasse 8 
CH-7302 Landquart 
Study Title: 
The Psychophysiological Effect of Terrestrial Altitude and Normobaric Hypoxia 
- A Randomized Clinical Trial 
Short Title / Study 
ID: 
The Effect of Terrestrial Altitude and Normobaric Hypoxia 
Protocol Version 
and Date: 
Version 02 from 01.05.2019 
Trial registration: 
Cantonal Ethics Committee Zurich  
Study category 
and Rationale 
Other clinical trials of category A according to the ClinV (Art. 20)  
Clinical Phase: 
- 
Background and 
Rationale: 
Research has consistently shown that exposure to extreme environments (i.e., 
cold, at altitude) can impair cognitive function (Taylor, Watkins, Marshall, 
Dascombe, & Foster, 2015). For logistical reasons and to control the study set-
up in which the test is carried out, studies that want to investigate the effect of 
“height” are usually carried out in laboratories. By testing under such controlled 
conditions, researchers can remove any co-founding factors and isolate a 
specific stressor, allowing them to better understand the mechanisms by which 
impairment can occur. However, when people are exposed to such 
environments as “height” in the “real world”, they often experience a number of 
other additional stressors at the same time, which could produce different 
results compared to laboratory studies. Surprisingly, however, little attention 
has been paid to the study of these additional stressors in combination (Tipton, 
2012). 
The best example of multiple stressors that occur In combination Is when 
climbing to high altitudes. Although the percentage of oxygen remains constant 
at different altitudes (20.93%), the air pressure decreases exponentially as the 
altitude increases. As a result, the oxygen partial pressure in the arterial blood 
and tissues is reduced (hypoxia), which leads to a deterioration in both physical 
and cognitive performance. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 9 from 61 
 
Objective(s): 
The aim of this study is to compare the psychophysiological effects of terrestrial 
altitude with a normobaric, hypoxic situation.  
Outcome(s): 
Primary results: 
Physiological measurements 
- 
Perfusion of the skin microcirculation (flux) 
- 
Blood oxygen saturation (%) 
- 
Oxygen saturation of the muscles (%)  
- 
Oxygen saturation of the brain (%) 
- 
Heart rate (b/min) 
- 
Blood pressure (mm/Hg) 
- 
Skin temperature (°C) 
- 
Lactate (mmol/l)  
- 
Creatine kinase (U/L) 
- 
Balance test (° & m/sec) 
- 
Pain sensation (N) 
 
Psychological measurements  
- 
Sleep Disorder Questionnaire  
- 
Lake Louis Altitude Sickness Questionnaire  
- 
Dyspnea questionnaire  
- 
State of mind questionnaire  
- 
Stanford Sleepiness Questionnaire 
- 
Automated, cognitive test battery 
 
 
Secondary results:  
- 
Thermal comfort and heat perception 
 
 
Study design: 
Randomized, clinical, crossover study 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 10 from 61 
 
Inclusion / 
Exclusion 
criteria: 
Inclusion criteria: 
- 
Healthy, adult aged 18 to 50 years 
- 
No cardiovascular diseases and/or interventions 
- 
no surgical interventions on the cardiovascular system.  
- 
No current injuries and/or pain conditions  
- 
Regular and sufficient sleep 
- 
No terrestrial altitude of 1000 m exceeded in the last month (including 
flights) 
- 
Not exposed to any form of hypoxia in the last month 
Exclusion criteria: 
- 
Age over 50 years 
- 
Current injuries of any kind and/or pain conditions  
- 
Acute and/or chronic pain conditions  
- 
Known general diseases (e.g. diabetes mellitus) 
- 
Fear of hypoxia  
- 
Fear of heights or sensitivity to terrestrial altitude 
- 
Regular intake of medication (including self-purchased medication), 
with the exception of anticonception drugs 
- 
Cardiovascular disease or abnormalities 
- 
Abnormalities of blood analysis or ECG 
- 
Psychological illnesses 
- 
Pregnancy / breastfeeding 
 
Preparation 
Subject recruitment 
The subject information and declaration of consent are submitted. Questions 
may be asked. If the subject agrees with the information, he or she will be 
summoned to the first day of contact.  
This includes the explanations on site, the signature of the declaration of 
consent and the completion of the health questionnaire. The pregnancy test 
must be negative (women only). If all tests are passed, an appointment is made 
for the intervention.  
 
Test Subject Preparation Measurement Day 
The test subject lies down on a couch in his underwear. This is followed by the 
20-minute room acclimatization phase in the same storage. The room 
temperature is kept as constant and neutral as possible (deviation of +/-2°C).  

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 11 from 61 
 
Measurements 
and procedures: 
During the 20-minute acclimatization phase, the application areas are drawn 
(skin-friendly pen) and the appliances are attached. If necessary, the hypoxia 
mask is then put on, the treatment is started and the baseline measurements 
are carried out. After the baseline measurement, the 5-minute step-up task is 
performed. After this task, the physiological parameters are measured again. 
These measurements were followed by a 5-minute cold water bath of the 
hand. Afterwards, the physiological measurements are carried out up to 30 
minutes after the cold water bath (5 min interval) and the questionnaires are 
filled out afterwards. In the terrestrial altitude situation, the test subject spends 
the night in the Hohsaas mountain restaurant (https://www.hohsaas-
bergrestaurant.ch, canton of Valais) and the measurements are repeated the 
next day.  
 
Perfusion of skin microcirculation  
The perfusion of the skin microcirculation is visualized using the Laser Speckle 
Contrast Imager (moorFLPI 2, moor instruments, www.moor.co.uk). This 
measurement is measured during the baseline measurements, after the step-
up task and up to 30 min after the cold water bath of the hand (5 min interval).  
Oxygen saturation of the muscles and brain  
The oxygen saturation of the muscles and brain is measured non-invasively 
with a deep tissue oxygenation monitor (moorVMS-NIRS, moor instruments, 
www.moor.co.uk). For this purpose, adhesive electrodes are attached over the 
muscle and forehead. This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water 
bath of the hand (5 min interval). 
Oxygen saturation of the blood 
The oxygen saturation of the blood is measured with a portable pulse oximeter 
with finger clip probe (Nonin 7500, Nonin medical B.V., Plymouth, USA). This 
measurement is measured during the baseline measurements, after the step-
up task and up to 30 min after the cold water bath of the hand (5 min interval). 
Blood pressure and heart rate 
The heart rate is measured with a heart rate belt and an additional 2-point ECG 
(Actiheart, Camntech Ltd., Cambridge, UK). Blood pressure is determined by 
means of an electronically automated upper arm blood pressure meter (Boso-
Medicus uno). This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water 
bath of the hand (5 min interval). 
Skin temperature 
Skin temperature is measured via the iButton system (www.ibuttonlink.com). 
The self-adhesive sensors transmit the information about the skin temperature 
wirelessly to a computer. Furthermore, the skin temperature is recorded by 
means of a thermal imaging camera (FLIR). This measurement is measured 
during the baseline measurements, after the step-up task and up to 30 min 
after the cold water bath of the hand (5 min interval). 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 12 from 61 
 
Measurements 
and procedures: 
Lactate and creatine kinase 
The lactate and creatine kinase measurement are carried out by capillary blood 
measurement (Accutrend, Roche Diagnostic, Rotkreuz, Switzerland & 
Reflotron, Roche Diagnostic, Rotkreuz, Switzerland). This measurement is 
measured during the baseline measurements, after the step-up task and up to 
30 min after the cold water bath of the hand (5 min interval). 
Balance measurement 
The fluctuations of the hull are recorded and evaluated with the Sway StarÔ 
System (www.b2i.info). The Sway StarÔ is a measuring instrument that 
contains gyroscopes. It is attached to a belt that is placed around the patient's 
waist. The data is evaluated with the associated Sway Star Ôsoftware and 
transferred to the data sheet. This measurement is carried out after the 
baseline measurement and after the cold water bath immersion of the hand.  
Pain sensation  
The pain threshold is measured using a pain pressure algometer (NOD, 
www.to-nod.com). This measurement is carried out after the baseline 
measurement and after the cold water bath immersion of the hand. 
Psychological measurements 
The psychological measurements (sleep disorder, altitude sickness, dyspnea, 
state of mind, drowsiness) are evaluated on the basis of written questionnaires.  
The cognitive test battery consists of 8 tasks (ANAM, US Department of 
Defence, Vista Life Sciences, USA), which are carried out on a laptop 
computer.  
These measurements are carried out after the baseline measurement and after 
the cold water bath immersion of the hand. 
Thermal comfort and temperature perception 
These parameters are measured using a scale. This measurement is carried 
out after the baseline measurement and after the cold water bath immersion of 
the hand .   
 
Further processing of the data 
Windows uses Excel for data pooling and the graphical representation of the 
end dataâ .   
Study Product / 
Intervention:  
Cloud 9  
Control 
Intervention (if 
applicable): 
As a control, the subjects are observed under normobaric and normoxic 
conditions.   
Number of 
Participants with 
Rationale: 
We limit the number of subjects to n = 24 study participants due to the available 
financial resources and due to the power analysis carried out. 
 
Study Duration: 
June 2019-December 2020 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 13 from 61 
 
Study Schedule: 
June 2019: planned start of measurements 
December 2020: planned end of measurements 
Investigator(s): 
Examiner 
- 
Dr. Ron Clijsen1,2,3 
- 
Dr. Erich Hohenauer1,2,3 
- 
Rahel Stoop, MSc1,2 
- 
Carlina Deflorin, MSc.1 
1.) University of Applied Sciences and Arts Southern Switzerland, 
Department of Business Economics, Health and Social Care, Physiotherapy 
Graubünden, Weststrasse 8, 7302 Landquart 
2.) THIM the International University of Physiotherapy, Weststrasse 8, 7302 
Landquart  
3.) Vrije Universiteit Brussel, Department of Movement and Sport Sciences, 
Pleinlaan 8, 1050 Brussels 
 
 
Contact / Director of Studies 
Dr. Clijsen Ron, PhD 
University of Applied Sciences and Arts Southern Switzerland  
Department of Business Economics, Health and Social Care 
Physiotherapy Graubünden  
Weststrasse 8, 7302 Landquart 
+41 81 300 01 75 
ron.clijsen@supsi.ch 
Study Centre(s): 
Single Centre Study: 
 
University of Applied Sciences and Arts Southern Switzerland 
Physiotherapy Graubünden 
Weststrasse 8 
7302 Landquart 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 14 from 61 
 
Statistical 
Considerations: 
Psychophysiological changes between terrestrial altitude and normobaric 
hypoxia - a randomized clinical trial. 
Repeated measures analysis of variance (MANOVA) 
2 Factors (Physiological Parameters) 
- 
Situation (terrestrial altitude vs. simulated altitude) 
- 
Time (baseline, after step-up task, 0, 5, 10, 15, 20, 25, 30 min post-
cold water immersion of the hand) 
2 factors (psychological parameters, balance, thermal comfort, temperature 
perception) 
- 
Situation (terrestrial altitude vs. simulated altitude) 
- 
Time (baseline, post-cold water immersion of the hand) 
- 
 
The significance level is set at P < 0.05, and the statistical data analysis is 
carried out with SPSS V. 26. 
GCP Statement: 
This study will be conducted in compliance with the protocol presented here, 
the current version of the Declaration of Helsinki, the ICH-GCP, ISO EN 
14155 (where applicable), and the Swiss Human Research Ordinance HFV. 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 15 from 61 
 
Overview of the study  
It has already been shown in previous studies that various environmental conditions can change both 
the physiology and psychology of humans (Taylor et al., 2015). For logistical reasons and due to other 
scientific considerations such as the comparability of results, investigations such as the investigation of 
"height" are carried out under laboratory conditions. By testing under such controlled conditions, 
researchers can remove any co-founding factors and isolate the cause of stress, allowing them to better 
understand the mechanisms by which impairment can occur. However, when exposed to such "real 
world" environments, they often experience a number of other additional stressors at the same time, 
which can also affect their performance. Surprisingly, however, little attention has been paid to the study 
of these additional stressors in combination (Tipton, 2012). 
The best example of multiple stressors that occur in combination is when climbing to high altitudes. 
Although the percentage of oxygen remains constant at different altitudes (20.93%), the air pressure 
decreases exponentially as the altitude increases. As a result, the oxygen partial pressure in the arterial 
blood and tissues is reduced (hypoxia), which leads to a deterioration in both physical and cognitive 
performance. However, in addition to the stressful effects of hypoxia, there can also be other extreme 
stressors, such as temperature fluctuations, which are known to significantly affect cognitive function 
(McMorris, Hale, Barwood, Costello, & Corbett, 2017). 
The reduced oxygen level in the blood during exposure at high altitude leads to a disturbance of sleep. 
This happens through changes in breathing during sleep. Consequently, sleep at altitude is 
characterized by a reduction in total sleep, sleep efficiency, and sleep quality (de Aquino Lemos et al., 
2012). 
While both hypoxia and sleep deprivation are reported to have negative effects on cognitive 
performance at rest, this may not be true when a person is exercising or moving. A light activity (such 
as a step-up task) may be enough to change the psychophysiological responses. It is known that 
cognitive performance improves with normoxia with light moderate exercise (Chang, Labban, Gapin, & 
Etnier, 2012). In addition, there is growing evidence that exercise can even cancel out the negative 
effects of hypoxia on cognitive performance (Ando et al., 2013; Komiyama et al., 2017). Another point 
that gives rise to further investigations in the field of hypoxia is the sensation of pain. It has already been 
shown in previous studies that the sensation of pain differs between normoxic and hypoxic situations 
(Noel-Jorand, Bragard, & Plaghki, 1996). To the knowledge of the authors, however, there are only 
limited studies that compare these parameters in a laboratory condition with the reactions in the real 
world. Many people suffer from lung dysfunction (such as COPD) and are therefore at least partially 
under hypoxic conditions. With this study, we can contribute to understanding the psychophysiological 
reactions under hypoxia.   
 
Aim of the study 
The aim of this study is to evaluate and compare the psychophysiological changes during terrestrial and 
simulated altitude. These changes will be investigated after a 5-minute step-up task and after a 5-minute 
cold water immersion of the hand in a) a normobaric, normoxic situation, b) normobaric, hypoxic situation 
and c) hypoxic, hypobaric situation.    
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 16 from 61 
 
Abbreviations 
 
CEC 
Competent Ethics Committee 
GCP 
Good Clinical Practice  
Ho 
Zero hypothesis 
H1 
Alternative hypothesis 
KlinV 
Ordinance on Clinical Trials in Human Research 
Masl. 
meters above sea level 
hPa 
Hectopascals 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 17 from 61 
 
Study Schedule  
The completion of the measurement series is planned for October 2019, and the completion of the 
entire project for December 2020. 
 
Table 1: Schedule 
 
 
January-February 
March 
April-June 
July-October 
November-
December 
2019 
 
 
Subject information, 
screening, planning, 
data collection 
Subject information, 
screening, planning, 
data collection 
Statistics  
2020 
Writing the article 
Writing the  
Article 
Writing the  
Article 
Publishing the article 
Publishing the 
article 
  
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 18 from 61 
 
1 
STUDIEN-ADMINISTRATION 
1.1 
Sponsor  
Thim van der Laan AG  
Weststrasse 8  
7302 Landquart 
 
Thim van der Laan jr.  
+41 81 300 01 70 
t.vanderlaan@physioschule.ch 
1.2 
Investigator 
 
University of Applied Sciences and Arts Southern Switzerland 
Department of Business Economics, Health and Social Care 
Physiotherapy Graubünden  
 
 
Dr. Ron Clijsen, PhD 
 
Weststrasse 8 
7302 Landquart 
 
+41 81 300 01 75 
ron.clijsen@supsi.ch 
1.3 
Examiner 
 
Investigator 
Dr. Ron Clijsen, PhD1,2,3 (GCP Module I – III & GCP Basic Course, Advanced Course Sponsor-
Investigator) 
Selection of subjects, obtaining consent to study participation, study administration, implementation of the 
Measurements – collecting data, analyzing data, interpreting data, writing a report 
University of Applied Sciences and Arts Southern Switzerland 
Department of Business Economics, Health and Social Care 
 
Head of Research at the University of Applied Sciences and Arts Southern Switzerland  
Weststrasse 8, 7302 Landquart 
+41 81 300 01 75 
ron.clijsen@supsi.ch 
 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 19 from 61 
 
Other examiners 
Dr. Erich Hohenauer, PhD1,2,3 (GCP Module I-III & GCP Basic Course) 
Selection of subjects, obtaining consent to study participation, study administration, implementation of the 
Measurements – collecting data, analyzing data, interpreting data, writing a report 
Rahel Stoop, MSc1 (GCP Module I-III & GCP Basic Course) 
Data analysis, carrying out measurements – collecting data , interpreting results 
Carlina Deflorin1 (GCP Module I-III & GCP Basic Course) 
Data analysis, execution of measurements – collection of data, interpretation of results 
 
1 University of Applied Sciences and Arts Southern Switzerland, Department of Business Economics, 
Health and Social Care, Physiotherapy Graubünden, Weststrasse 8, 7302 Landquart 
2 THIM the International University of Physiotherapy, Weststrasse 8, 7302 Landquart  
3 Vrije Universiteit Brussel, Department of Movement and Sport Sciences, Pleinlaan 8, 1050 Brussels 
 
Other employees 
Tom Williams, PhD Student 
Interpretation of the data, writing of the report 
 
University of Portsmouth  
Department of Sport & Exercise Science  
Spinnaker Building, Cambridge Road,  
Portsmouth, Hampshire, P012ER 
 
+44 239284 5366 
thomas.williams@port.ac.uk 
 
Dr. med. Andreas Steiner  
Medical monitoring during the study 
 
Blauenstrasse 41 
CH-4104 Oberwil 
Switzerland  
+41 612 716 141 
asteiner@hin.ch 
 
1.4 
Statistician 
 
Prof. Dr. Tom Deliens, PhD 
 
Virje Universiteit Brussel  
Department of Movement and Sport Sciences  
Pleinlaan 8, 1050 Brussels 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 20 from 61 
 
+32 2 629 20 10 
tom.deliens@vub.be 
 
1.5 
Laboratory Manager (Investigator) 
 
Dr. Ron Clijsen, PhD 
 
Head of Research Laboratory  
University of Applied Sciences and Arts Southern Switzerland 
Department of Business Economics, Health and Social Care  
Weststrasse 8 
7302 Landquart 
 
+41 81 300 01 75 
ron.clijsen@supsi.ch 
 
1.6 
Monitoring of the study 
Dr. Joseph Costello 
University of Portsmouth  
Department of Sport & Exercise Science  
Spinnaker Building, Cambridge Road,  
Portsmouth, Hampshire, P012ER 
 
+44 239284 5366 
joe.costello@port.ac.uk 
 
1.7 
Privacy 
All data obtained from study participants will be coded and not passed on to other people. Personal data 
and personal details are stored in paper form in a locked filing cabinet. The head of the research 
laboratory and at the same time the head of the study has access here, and the administration of the 
documents also falls within his area of responsibility. 
All digital data is encrypted and encoded. No conclusions can be drawn about individuals. The digital 
data is stored on internal computers, archived and not released to outsiders. 
Employees involved in data processing have no insight into the personal data and the coding of it. 
 
1.8 
Other committees or institutes involved  
The study is being conducted in the research laboratory at the University of Applied Sciences and Arts 
Southern Switzerland, Physiotherapy Graubünden, Weststrasse 8, 7302 Landquart, Switzerland. 
The test products and measuring equipment are all located in this room and therefore all measurements 
can be carried out at the same location. The room offers enough space. 
At present, no further studies with this arrangement are taking place in this experimental laboratory. 
During this period, no studies will take place in our laboratory. 
No other institutes and committees are involved in this study or in the approval or monitoring of the study. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 21 from 61 
 
2 
 ETHNIC & REGULATORY ASPECTS 
2.1 
Study Registration 
The implementation of the present study is the responsibility of the Cantonal Ethics Committee Zurich. 
An application for admission is submitted. Any further conditions of the responsible ethics committee 
must be implemented in the study protocol. 
When the study protocol is submitted to the Cantonal Ethics Committee in Zurich, the study is also 
registered with the Swiss Coordination Office for Research on Human Subjects. In addition, the study 
will be registered in a WHO-recognized primary registry (clinicaltrials.gov). 
 
2.2 
Categorization of the study  
The study is categorized as another clinical trial of risk category A (ClinO, Art. 20). The subjects are 
taken to terrestrial and simulated altitudes. Neither tissue samples nor other invasive methods are 
performed. The simulated height is carried out with a CE certified device according to the instructions 
for use. 
 
2.3 
Competent Ethics Committee (CEC)  
Human research in the Canton of Graubünden falls under the remit of the Cantonal Ethics Commission 
Zurich. Changes to the study protocol are not permitted without the prior consent of the CEC, except for 
the immediate elimination of obvious hazards to the participants. According to chap. 2.10 to the CEC. 
An early termination or interruption of the study must be reported to the CEC within 15 days, and the 
regular end within 90 days. The final report must be submitted within one year of the end of the 
programme. Corrections are to be reported in accordance with Chapter 2.10.  
 
2.4 
Competent Authorities (CA)  
The present study falls under the remit of the Cantonal Ethics Committee Zurich. Obligations and 
deadlines can be found in the previous point. 
 
2.5 
Ethical Leadership of the Study 
The study will be conducted in accordance with this protocol and the current version of the Helsinki 
Declaration, the ICH-GCP, the European Medical Device Directive 93/42/EEC and the ISO standard 
14155 and ISO 14971 (where applicable), as well as the Swiss Human Research Ordinance and thus 
Swiss law. 
The CEC receives an annual report and is informed about the course of studies.  
 
2.6 
Conflict 
There is no financial conflict of interest on the part of the sponsor/investigator, nor is there a 
corresponding relationship of dependency. 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 22 from 61 
 
2.7 
Patient information and informed consent 
The examiners will explain to each participant individually the nature of the study, its content, intent and 
objective. This includes the protocol flow, approximate time duration, possible risks and benefits. The 
participant is informed that participation is voluntary and can be withdrawn from the study at any time, 
without personal consequences of any kind. The participant will be informed about data protection, the 
handling of personal data and their access. 
Each participant receives written subject information and the declaration of consent with the detailed 
study description and all necessary information to be able to decide whether to participate in the study. 
The participant will also be given sufficient time to read this written information and to ask questions to 
the responsible examiners. 
The subject information and the informed consent form are submitted to the CEC, where they must be 
reviewed and approved.  
The signed declaration of consent must be submitted before the start of the study process. The 
participant should read them before signing and check their contents. The responsible examiner then 
also signs the declaration of consent. Finally, the participant receives a copy of the declaration of 
consent. The signed declaration of consent is kept in the original as a study document in a locked filing 
cabinet. 
 
2.8 
Confidentiality & Privacy 
The examiners ensure that the privacy of the participants is maintained. In particular, data protection 
and confidentiality are guaranteed, and no personal data is presented or published. The signed 
declaration of consent, as well as the completed questionnaire with the other personal details, are kept 
in the original as a study document in a locked filing cabinet. 
The digital data is encrypted and treated confidentially, and access to the personal data is denied to 
third parties. The digital data collected is stored solely on the institute's own computers and is not passed 
on to any external persons or transferred to other computers. 
Direct access to the personal data is allowed only to the head of the research laboratory (study leader), 
as well as authorized persons of the CEC. 
 
2.9 
Early termination of the study  
The sponsor or the principal investigator or physician present may discontinue the study early if/if: 
- 
ethical concerns 
- 
insufficient number of subjects 
- 
the safety of the participants cannot be guaranteed 
- 
Findings from clinical practice make it pointless to continue the study 
- 
early evidence or harm of the experimental intervention has been proven 
- 
the health of the subjects is at risk 
 
2.10 Adjustments to the protocol 
Adjustments and changes to the current study are only permissible after review by the CEC. 
Short-term changes to the protocol prior to an audit by the CEC may be made to ensure the rights and 
safety of participants. However, such adjustments must be documented and reported to the CEC as 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 23 from 61 
 
soon as possible. 
Significant changes are only permissible after a review of the CEC. Any other changes must be notified 
to the CEC as soon as possible and listed in the annual report. 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 24 from 61 
 
3 
BACKGROUND AND RATIONALE  
3.1 
Background and justification 
Research has consistently shown that exposure to extreme environments (i.e., hot, cold, altitude) can 
impair cognitive function (Taylor et al., 2015). For logistical reasons and to better control the (climatic) 
conditions in which the subjects are tested, most of these tests are carried out in laboratories. By testing 
under such controlled conditions, researchers can remove any co-founding factors and isolate the cause 
of stress, allowing them to better understand the mechanisms by which impairment can occur. However, 
when exposed to such "real world" environments, they often experience a number of other additional 
stressors at the same time, which can also affect their performance. Surprisingly, however, little attention 
has been paid to the study of these additional stressors in combination (Tipton, 2012). 
 
The best example of multiple stressors that occur in combination is when climbing to high altitudes. 
Although the percentage of oxygen remains constant at different altitudes (20.93%), the air pressure 
decreases exponentially as the altitude increases. As a result, the oxygen partial pressure in the arterial 
blood and tissues is reduced (hypoxia), which leads to a deterioration in both physical and cognitive 
performance. However, in addition to the stressful effects of hypoxia, other stressors, such as 
temperature and fatigue, can also be added, which are known to significantly affect human functions 
(McMorris et al., 2017). 
The reduced oxygen level in the blood during exposure at high altitude causes breathing disorders 
during sleep. Consequently, sleep at altitude is characterized by a reduction in total sleep, sleep 
efficiency, and sleep quality (de Aquino Lemos et al., 2012). 
While both hypoxia and sleep deprivation are reported to have negative effects on cognitive 
performance at rest, this may not be true when a person is exercising or moving. It is known that 
cognitive performance improves with normoxia with light moderate exercise (Chang et al., 2012). In 
addition, there is growing evidence that exercise can even cancel out the negative effects of hypoxia on 
cognitive performance (Ando et al., 2013; Komiyama et al., 2017). Another point that gives rise to further 
research in the field of hypoxia is the sensation of pain. It has already been shown in previous studies 
that the sensation of pain differs between normoxic and hypoxic situations (Noel-Jorand et al., 1996). 
To the knowledge of the authors, however, there are only limited studies that compare these parameters 
in a laboratory condition with the reactions in the real world. In addition, various patient groups also 
suffer from lung dysfunction (such as COPD) and are therefore at least partially under hypoxic conditions. 
With this study, we can contribute to understanding the psychophysiological reactions under hypoxia.   
 
 
Aim of the study 
The aim of this study is to evaluate and compare the psychophysiological changes during terrestrial and 
simulated altitude. These changes will be investigated after a 5-minute step-up task and after a 5-minute 
cold water immersion of the hand in a) a normobaric, normoxic situation, b) normobaric, hypoxic situation 
and c) hypoxic, hypobaric situation.    
 
3.2 
Medical product and indication 
Simulated altitude training is quickly becoming the most promising development in the world in terms of 
athletic performance and peak fitness.  
With the Cloud 9, a simulated altitude of 2700 m and 3530 m above sea level can be achieved. This 
corresponds to an oxygen partial pressure of 15.0% and 13.5% respectively. The Cloud 9 altitude 
training device is designed for all levels of sports (including athletes) who want to improve their 
performance. The Cloud 9 is a solid, certified product that complies with the European Directives on 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 25 from 61 
 
Electromagnetic Compatibility, Machinery Directive, Air Pressure Equipment and Low Voltage 
Equipment (89/336/EEC, 91/368/CEE, 93/68/CEE, 97/23/EC, EN61010-1).  
 
Cloud 9 mapping: https://chasingtargets.eu/altitude-tent-rental-service/ 
 
 
3.3 
Preclinical evidence 
 
Studies under hypoxic conditions have already been carried out in the medical field with a wide variety 
of pathologies, such as obesity under stress(Girard, Malatesta, & Millet, 2017; Park, Jung, Kim, & Lim, 
2019) but also with seniors (Pramsohler et al., 2017). Hypoxic conditions can lead to psychological 
changes in addition to physiological changes (Taylor et al., 2015). Chronic stays at altitude can further 
lead to a physiological change (Smith et al., 2014) 
It is known that cognitive and physical performance improves with normoxia with light moderate exercise 
(Chang et al., 2012). In addition, there is growing evidence that exercise can even cancel out the 
negative effects of hypoxia on cognitive performance (Ando et al., 2013; Komiyama et al., 2017).  
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 26 from 61 
 
3.4 
Current clinical evidence 
According to the authors' knowledge, there are currently hardly any clinical studies that contrast the 
psychophysiological effects of terrestrial altitude with simulated altitude.  
 
3.5 
Medical product: method of application in the study  
During the normobaric, hypoxic situation, an altitude of 3530 m above sea level is simulated, which 
corresponds to an oxygen partial pressure of 13.5%. This situation is realized by a mask system, with 
the help of Cloud 9.  
 
https://trainingwithaltitude.co.uk/product/altitude-mask/ 
3.6 
Peers 
The intervention group is also the control group, as a crossover design is used.  
 
Randomization 
Randomization takes place according to the situation (normobar & normoxic vs. normobar & hypoxic). 
The situation you find yourself in first is decided by drawing lots.  
 
3.7 
Risk / Benefits 
Possible risks in the situation of terrestrial and simulated altitude are the appearance of headaches, 
impaired consciousness, disorientation and nausea. In addition, a doctor is present during the 
measurements. Subjects who may be at risk are recorded by the screening procedure and the health 
questionnaire and are not included in the study. However, the risk is to be classified as minor, as studies 
are already being conducted with obese patients and seniors under hypoxic conditions, which has not 
led to any complications. Participants do not derive direct benefits from participating in the study. More 
information on securing the test subjects can be found in chap. 8.1.1.Justification 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 27 from 61 
 
for the choice of population  
This series of studies is being conducted with healthy adults to minimize the health risk. The 
psychophysiological reactions of the body to terrestrial and simulated altitude training are assumed to 
be probable in this test subject population. 
 
The test subjects are comprehensively informed about the course of the study and possible risks before 
they are accepted to participate in the study. You will also receive the information in written form and 
have the opportunity to ask questions if anything is unclear. The declaration of consent explains to them 
what their rights and obligations are when participating. In addition, they are informed that they may 
withdraw from participation at any time without giving reasons, without incurring any disadvantages as 
a result.  
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 28 from 61 
 
4 
STUDY OBJECTIVES  
4.1 
General objectives 
The aim of this study is to evaluate and compare the psychophysiological changes during terrestrial and 
simulated altitude. These changes will be investigated after a 5-minute step-up task and after a 5-minute 
cold water immersion of the hand in a) a normobaric, normoxic situation, b) normobaric, hypoxic situation 
and c) hypoxic, hypobaric situation. 
4.2 
Primary objectives 
The primary goal is to compare and evaluate the physiological effects of terrestrial altitude and simulated 
altitude. For this purpose, the following parameters are measured:  
Objective parameters: 
- 
Perfusion of the skin microcirculation (flux) 
- 
Blood oxygen saturation (%) 
- 
Oxygen saturation of the muscles (%)  
- 
Oxygen saturation of the brain (%) 
- 
Heart rate (b/min) 
- 
Blood pressure (mm/Hg) 
- 
Skin temperature (°C) 
- 
Lactate (mmol/l)  
- 
Creatine kinase (U/L) 
- 
Balance test (° & m/sec) 
 
Subjective parameters:  
- 
Pain sensation (N) 
 
The primary goal is to compare and evaluate the psychological effects of terrestrial altitude and 
simulated altitude. For this purpose, the following parameters are measured:  
 
Subjective parameters: 
- 
Sleep Disorder Questionnaire  
- 
Lake Louis Altitude Sickness Questionnaire  
- 
Dyspnea questionnaire  
- 
State of mind questionnaire  
- 
Stanford Sleepiness Questionnaire 
- 
Automated, cognitive test battery 
 
 
4.3 
Secondary Objectives  
The secondary goal is to compare and evaluate thermal comfort and temperature perception according 
to terrestrial altitude and simulated altitude. For this purpose, the following parameters are measured:  
- 
 
Subjective parameters: 
- 
Thermal comfort  
- 
Temperature sensation 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 29 from 61 
 
4.4 
Other safety aspects (long-term) 
No more risks than those discussed so far are to be expected in this study. 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 30 from 61 
 
5 
STUDENT OUTCOMES  
5.1 
Primary outcomes 
 
Perfusion of skin microcirculation  
The perfusion of the skin microcirculation is visualized using the Laser Speckle Contrast Imager 
(moorFLPI 2, moor instruments, www.moor.co.uk). The "moorFLPI-2 Full-Field Laser Perfusion Imager" 
measures blood flow measured in flow rates (arbitrary units) of the skin's microcirculation. The laser is 
intended for clinical and physiological research. The fabric is illuminated with a divergent infrared laser 
beam. The laser measures down to a depth of 1mm, so it mainly detects the superficial blood flow, 
speed and concentration of red blood cells. This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water bath of the hand (5 min 
interval).  
 
Oxygen saturation of the muscles and brain  
The oxygen saturation of the muscles and brain is measured non-invasively with a deep tissue 
oxygenation monitor (moorVMS-NIRS, moor instruments, www.moor.co.uk). For this purpose, adhesive 
electrodes are attached over the muscle and forehead. This measurement is measured during the 
baseline measurements, after the step-up task and up to 30 min after the cold water bath of the hand 
(5 min interval). 
 
Figure: Measurement of oxygen saturation of the brain and muscles 
 
 
 
 
 
 
 
 
Oxygen saturation of the blood 
The oxygen saturation of the blood is measured with a portable pulse oximeter with finger clip probe 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 31 from 61 
 
(Nonin 7500, Nonin medical B.V., Plymouth, USA). This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water bath of the hand (5 min 
interval). 
 
 
Figure: Measurement of the oxygen content of the blood 
 
Blood pressure and heart rate 
The heart rate is measured with a heart rate belt and an additional 2-point ECG (Actiheart, Camntech 
Ltd., Cambridge, UK). Blood pressure is measured by means of an electronically automated upper arm 
blood pressure monitor (Boso-Medicus uno). This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water bath of the hand (5 min 
interval). 
 
Skin temperature 
Skin temperature is measured via the iButton system (www.ibuttonlink.com). The self-adhesive sensors 
transmit the information about the skin temperature wirelessly to a computer. Furthermore, the skin 
temperature is recorded by means of a thermal imaging camera (FLIR). This measurement is measured 
during the baseline measurements, after the step-up task and up to 30 min after the cold water bath of 
the hand (5 min interval). 
 
Lactate and creatine kinase 
The lactate and creatine kinase measurement are carried out by capillary blood measurement 
(Accutrend, Roche Diagnostic, Rotkreuz, Switzerland & Reflotron, Roche Diagnostic, Rotkreuz, 
Switzerland). The affected area is disinfected and a superficial wound is pierced to take capillary blood. 
This measurement is measured during the baseline measurements, after the step-up task and up to 30 
min after the cold water bath of the hand (5 min interval). 
 
Balance measurement 
The fluctuations of the hull are recorded and evaluated with the Sway StarÔ System (www.b2i.info). 
The Sway StarÔ is a measuring instrument that contains gyroscopes. It is attached to a belt that is 
placed around the patient's waist. The data is evaluated with the associated Sway Star Ôsoftware and 
transferred to the data sheet. This measurement is carried out after the baseline measurement and after 
the cold water bath immersion of the hand.  

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 32 from 61 
 
 
Figure: Measuring balance with the Sway StarTM 
 
Pain sensation 
The pain threshold is measured using a pain pressure algometer (NOD, www.to-nod.com). As soon as 
the patient reports pain, this measurement is stopped. This measurement is carried out after the baseline 
measurement and after the cold water bath immersion of the hand. 
 
Psychological measurements 
The psychological measurements (sleep disorder, altitude sickness, dyspnea, state of mind, 
drowsiness) are evaluated on the basis of written questionnaires.  
The cognitive test battery consists of 8 tasks (ANAM, US Department of Defence, Vista Life Sciences, 
USA), which are carried out on a laptop computer.  
These measurements are carried out after the baseline measurement and after the cold water bath 
immersion of the hand. 
 
5.2 
Secondary outcomes 
Thermal comfort and temperature perception 
This parameter is measured using a scale. The test subjects indicate their subjective temperature 
perception on a 9-point scale from -4 (very cold) to +4 (very hot). They then rate the thermal comfort 
between 0 (pleasant) and 4 (extremely unpleasant) on a 5-point scale. These measurements are carried 
out after the baseline measurement and after the cold water bath immersion of the hand. 
 
5.3 
Security considerations 
No further results are recorded that would serve safety. 
Discontinuation of the experiment is the responsibility of the examiner with regard to the subject's 
subjective feelings and expressions. 
If a test subject does not feel well during the application according to his or her subjective assessments, 
he or she can discontinue the experiment and withdraw participation in the study without any 
disadvantages. A doctor is also present to ensure the safety of the test subjects. 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 33 from 61 
 
6 
STUDIENDESIGN  
Study design and justification 
 
Randomized, clinical, crossover study 
This is a category A intervention study (ClinO, Art. 20), whereby the intervention involves testing a tested 
product on healthy volunteers. The group size is N = 24. The intervention product (Cloud 9) is a solid, 
certified product that complies with the European Directives on Electromagnetic Compatibility, 
Machinery Directive, Air Pressure Equipment and Low Voltage Equipment (89/336/EEC, 91/368/CEE, 
93/68/CEE, 97/23/EC, EN61010-1. 
 
6.1 
Method for minimizing influencing factors 
6.1.1 
Randomization  
The situation (normobar & normoxic vs normobar & hypoxic) will be randomized. The randomization 
procedure is carried out by lottery. 
 
6.1.2 
Blinding  
Blinding the test subjects is not possible with regard to the situation.  
It is not possible to blind the data collectors.  
However, blinding the statistician can be guaranteed, who has no access to the personal data of the 
test persons and is not present during the data collection. 
 
6.1.3 
Other Methods 
No other methods are used. 
 
6.2 
Procedure for unblinding (code break)  
There is no provision for the statistician to be blinded.  
 
6.3 
Procedure for unblinding (code break)  
Blinding (coding) of study participants is only permitted if an unforeseen incident or medical problems 
occur during or after the completion of study participation in a subject, which may be attributable to 
participation in the study.  
For incidents (AE) that occur during or shortly after the simulated altitude (within the first 24 hours) and 
can potentially be attributed to the intervention, the principal investigator may, at his or her discretion, 
immediately waive the blinding of the study participant and the investigators present to ensure adequate 
treatment of the study participant.  
In the case of incidents (AE) that occur longer than 24 hours after the simulated altitude, clarification 
with a doctor is mandatory and a doctor's certificate is required for the lifting of blindness. Data may 
then also be passed on to the attending physician with the consent of the study participant concerned. 
This approach is justified because no life-threatening incidents are to be expected due to the intervention 
used here.  

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 34 from 61 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 35 from 61 
 
7 
STUDENT POPULATION  
7.1 
Inclusion Criteria 
 
 
Inclusion Criteria 
Exclusion criteria 
- 
Healthy, adult aged 18 to 50 years 
- 
No cardiovascular diseases and/or 
interventions 
- 
no surgical interventions on the 
cardiovascular system.  
- 
No current injuries and/or pain 
conditions  
- 
Regular and sufficient sleep 
- 
No terrestrial altitude of 1000 m 
exceeded in the last month (including 
flights) 
- 
Not exposed to any form of hypoxia in 
the last month 
- 
Signed consent form 
 
 
- 
Age over 50 years 
- 
Current injuries of any kind and/or pain 
conditions  
- 
Acute and/or chronic pain conditions  
- 
Known general diseases (e.g. diabetes 
mellitus) 
- 
Fear of hypoxia  
- 
Fear of heights or sensitivity to terrestrial 
altitude 
- 
Regular intake of medication (including 
self-purchased medication), with the 
exception of anticonception drugs 
- 
Cardiovascular disease or abnormalities 
- 
Abnormalities of blood analysis or ECG 
- 
Mental illnesses 
- 
Pregnancy / breastfeeding 
- 
Cognitive / linguistic inability to 
understand the study information or the 
study action.  
 
 
7.2 
Recruitment and Screening 
 
Recruitment 
It is advertised on the websites (homepage & Facebook) of "Thim van der Laan" and "SUPSI". In 
addition, information posters will be hung up in the school building. The exact texts have been prepared 
according to the checklist of the Cantonal Ethics Commission Zurich. 
 
As advertisements (text visible): 
• 
Homepage of the Physioschule Thim van der Laan: www.physioschule.ch and SUPSI: 
www.supsi.ch 
• 
Facebook page of the Thim van der Laan Physiotherapy School: 
https://www.facebook.com/physioschule and SUPSI: 
https://www.facebook.com/supsi.physiotherapie/ 
Screening 
During the first contact, the potential participants are informed about the course and risks of the study, 
as well as the conditions for and the amount of compensation explained. A checklist for contacting them 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 36 from 61 
 
by telephone serves as a basis. 
During the first telephone contact, a questionnaire is filled out by the study management to determine 
the suitability as a study participant. 
 
The checklist for the initial determination of suitability during the initial telephone contact can be found 
in the attachments. The advertisements and health questionnaires are also in the inserts. 
 
7.3 
Allocation of situations 
The situation assignment (normobar & normoxic vs. normobar & hypoxic) is done concealed by means 
of a lot in a sealed envelope, which is drawn under the supervision of the study leader. This lot shows 
whether the subject first goes through the normobaric & normoxic situation or the normobar & hypoxic 
situation.  
 
7.4 
Discontinuation of study participation 
If a participant withdraws from the study, the lot of the allocation is returned to the pot in a new envelope 
and a new participant is sought.  
All data collected to date will be evaluated as far as possible and included in the data analysis (in 
accordance with Art. 9 ClinO). After evaluation, the data is irreversibly anonymized. 
 
The conditions for the termination of the experiment were described in chap. 5.4.  
There is no disadvantage for the participants if they discontinue their participation in the study.  
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 37 from 61 
 
8 
STUDY INTERVENTION  
8.1 
Medical Device ID  
8.1.1 
Intervention product 
The intervention product is a certified product. With the Cloud 9, a simulated altitude of 2700 m and 
3530 m above sea level can be achieved. This corresponds to an oxygen partial pressure of 15.0% and 
13.5%, respectively. The Cloud 9 altitude training device is intended for everyone (even amateurs) who 
wants to increase their performance. The Cloud 9 is a solid, certified product that complies with the 
European Directives on Electromagnetic Compatibility, Machinery Directive, Air Pressure Equipment 
and Low Voltage Equipment (89/336/EEC, 91/368/CEE, 93/68/CEE, 97/23/EC, EN61010-1. 
 
Securing the test subjects 
Only subjects who have completed the health questionnaire without risk factors will be admitted to the 
study. In this way, risk factors are detected at an early stage and the subjects for the study are not 
recruited. In addition, a doctor is present during the measurements to ensure the safety of the test 
subjects. 
 
8.1.2 
Control intervention 
The control group will be observed under normobaric and normoxic conditions.  
 
8.1.3 
Packaging, labeling and use 
The Cloud 9 is a solid, certified product that complies with the European Directives on Electromagnetic 
Compatibility, Machinery Directive, Air Pressure Equipment and Low Voltage Equipment (89/336/EEC, 
91/368/CEE, 93/68/CEE, 97/23/EC, EN61010-1. 
 
8.1.4 
Storage 
The Cloud 9 can be stored both outside in the dry and inside a room. The equipment is located inside 
our laboratory for the duration of the measurements and is only accessible to laboratory staff. The room 
in which Cloud 9 is located is fully ventilated and has the following dimensions: 7m x 14m x 2.5m.   
 
8.2 
Administration of the experiment  
Since no prescription drugs or invasive methods are used, the experiment is not discussed further in 
chapters 8.2-8.4 and only chapter 9 is referred to.  
 
8.2.1 
Experimental intervention  
Simulated height: The test subjects are in the laboratory of our institution and are connected to Cloud 9 
by means of a mask. The subjects are exposed to a simulated altitude of 3530 m above sea level under 
normobaric conditions. This intervention is used to determine the psychophysiological effect under 
normobaric and hypoxic conditions.  
 
Terrestrial altitude: The subjects are at an SAC hut (Bergrestaurant Hohsaas: https://www.hohsaas-
bergrestaurant.ch) in the canton of Valais at an altitude of 3200 m above sea level. By means of this 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 38 from 61 
 
exposure, the psychophysiological effect under hypobaric and hypoxic conditions is determined. The 
test subjects spend a single night in this SAC hut and the measurements are repeated the next day.  
 
8.2.2 
Control intervention 
Control: The test subjects are in our laboratory under normobar and normoxic conditions. This situation 
serves as a control intervention, which is contrasted with the simulated and terrestrial situation.  
 
8.3 
Dosage, application modification  
In the simulated altitude situation, the recommendations in the Cloud 9 operating manual are followed.  
 
8.4 
Adherence to the study intervention 
The test subjects are neither motivated nor unnecessarily distracted by the examiners or the study 
director with conversations. Communication is kept to a minimum, only study-related discussions are 
conducted in order not to influence the psychophysiological effects and to ensure homogeneity.  
 
8.5 
Follow-up treatment of eliminated participants  
Data already collected from eliminated participants is stored anonymously in the filing cabinet provided 
for this purpose. As far as possible, the data will be included in the data analysis of the study.  
There is no disadvantage for the participants if they discontinue their participation in the study and no 
further interventions are necessary for follow-up treatment.  
If study participation was discontinued due to a reaction occurring during study participation, this will be 
logged and reported to the sponsor investigator (head of the research laboratory), study leader and 
supervisor of the study. If medical care is necessary, the report is forwarded to the business liability 
insurance of Thim van der Laan AG (Basler Versicherung) in order to ensure the appropriate follow-up 
treatment.  
 
8.6 
Preventive measurements 
Through the telephone assessment and the health questionnaire, the intake of medication, injuries and 
operations, as well as known relevant diseases and allergies are asked. In addition, only young and 
healthy subjects who have already been at this altitude and had no signs of altitude sickness are 
examined. Pregnant women or nursing mothers are not allowed to participate in the study. Subjects who 
assure the study leader that they are not pregnant are allowed to participate in the study. In case of 
uncertainty, the potential test subjects are provided with a pregnancy test free of charge. The test 
subjects must then present a negative pregnancy test (given away free of charge by us). The test result 
is noted on the health questionnaire.  
 
8.7 
Accompaniments 
No further side effects are expected from study participation. However, a doctor is present to detect 
unexpected side effects and react accordingly. 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 39 from 61 
 
8.8 
Liability 
The experiments are taking place in the research laboratory of the "Physiotherapie Graubünden" in 
Landquart and in the Hohsaas mountain restaurant (canton of Valais). The liability for the transport is 
assumed by the business liability insurance of Thim van der Laan AG (Basler Versicherung).  
 
8.9 
Return of the medical device 
Cloud 9 was purchased by the research department of the "University of Applied Sciences and Arts 
Southern Switzerland" and will remain in the research laboratory after the measurements have been 
completed.  
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 40 from 61 
 
9 
STUDY STRUCTURE & EVALUATION  
9.1 
Schedule Study Protocol 
1. Subject Information & Informed Consent 
30 min 
2. Preparation of the subject  
20 min 
3. Running the Test Log (Sublogs) 
 
 
 
Test protocol: Time required – maximum 90 min 
 
Normobar hypoxic vs. hypobar hypoxic vs. normobar normoxic 
Simulated Height (Cloud 
9) 
 
1.) Baseline measurements 
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
20 min   
 
2.) Step-up task 
 
5 min  
 
3.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Terrestrial Altitude 
 
1.) Baseline measurements 
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
20 min   
 
2.) Step-up task 
 
5 min  
 
3.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Control intervention 
 
1.) Baseline measurements 
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
20 min   
 
2.) Step-up task 
 
5 min  
 
3.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 41 from 61 
 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase  
 
10 min   
 
3.) Cold water immersion of 
the hand 
 
5 min 
 
4.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
40 min 
Skin temperature 
Lactate & Creatine Kinase  
 
10 min   
 
3.) Cold water immersion of 
the hand 
 
5 min 
 
4.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
40 min 
 
Skin temperature 
Lactate & Creatine Kinase  
 
10 min   
 
3.) Cold water immersion of 
the hand 
 
5 min 
 
4.) Follow-up  
Perfusion Microcirculation 
Oxygen Saturation Muscle & 
Brain 
Oxygen saturation of blood 
Blood Pressure & Heart Rate 
Skin temperature 
Lactate & Creatine Kinase 
Balance measurement 
Pain sensation 
Psychological measurements 
Thermal comfort & temperature 
perception 
 
40 min  
 
Test log 
Time exposure 
Visits 
Declaration of Consent 
30 min 
Unique 
Simulated Height 
20 + 90 min = 110 min 
Unique 
Terrestrial Altitude 
20 + 90 min = 110 min 
Twice (incl. 1x overnight stay) 
Control intervention  
20 + 90 min = 110 min 
Unique 
TOTAL TIME COMMITMENT 
470 min + 1 night 
 
 
Each test subject can expect a total time expenditure of 470 minutes excluding the journey to and 
from Valais and the overnight stay at the SAC mountain hut. 
9.1.1 
Measurement of primary results 
The primary measurements of perfusion of skin microcirculation, oxygen saturation of the muscles, brain, 
musculature as well as the measurement of blood pressure & heart rate, skin temperature, lactate, 
creatine kinase, pain sensation and balance can be measured within 10 min. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 42 from 61 
 
The psychological measurements, which are carried out on the basis of questionnaires, can be carried 
out within 10 minutes. 
 
9.1.2 
Measurement of primary results 
The primary measurements refer to the area of application, lumbar back area, right-sided or left-sided 
paravertebral depending on randomization. 
 
Perfusion of skin microcirculation  
The perfusion of the skin microcirculation is visualized using the Laser Speckle Contrast Imager 
(moorFLPI 2, moor instruments, www.moor.co.uk). This measurement is non-invasive. The "moorFLPI-
2 Full-Field Laser Perfusion Imager" measures blood flow measured in flow rates (arbitrary units) of the 
skin's microcirculation. The laser is intended for clinical and physiological research. The fabric is 
illuminated with a divergent infrared laser beam. The laser measures down to a depth of 1mm, so it 
mainly detects the superficial blood flow, speed and concentration of red blood cells. This measurement 
is measured during the baseline measurements, after the step-up task and up to 30 min after the cold 
water bath of the hand (5 min interval).  
 
Oxygen saturation of the muscles and brain  
The oxygen saturation of the muscles and brain is measured non-invasively with a deep tissue 
oxygenation monitor (moorVMS-NIRS, moor instruments, www.moor.co.uk). For this purpose, adhesive 
electrodes are attached over the muscle and forehead. This measurement is measured during the 
baseline measurements, after the step-up task and up to 30 min after the cold water bath of the hand 
(5 min interval). 
 
Oxygen saturation of the blood 
The oxygen saturation of the blood is measured with a portable pulse oximeter with finger clip probe 
(Nonin 7500, Nonin medical B.V., Plymouth, USA). This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water bath of the hand (5 min 
interval). 
 
Blood pressure and heart rate 
The heart rate is measured with a heart rate belt and an additional 2-point ECG (Actiheart, Camntech 
Ltd., Cambridge, UK). Blood pressure is measured by means of an electronically automated upper arm 
blood pressure monitor (Boso-Medicus uno). This measurement is measured during the baseline 
measurements, after the step-up task and up to 30 min after the cold water bath of the hand (5 min 
interval). 
 
Skin temperature 
Skin temperature is measured via the iButton system (www.ibuttonlink.com). The self-adhesive sensors 
transmit the information about the skin temperature wirelessly to a computer. Furthermore, the skin 
temperature is recorded by means of a thermal imaging camera (FLIR). This measurement is measured 
during the baseline measurements, after the step-up task and up to 30 min after the cold water bath of 
the hand (5 min interval). 
 
Lactate and creatine kinase 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 43 from 61 
 
The lactate and creatine kinase are carried out by capillary blood measurement (Accutrend, Roche 
Diagnostic, Rotkreuz, Switzerland & Reflotron, Roche Diagnostic, Rotkreuz, Switzerland). The affected 
area is disinfected and a superficial wound is pierced to take capillary blood. This measurement is 
measured during the baseline measurements, after the step-up task and up to 30 min after the cold 
water bath of the hand (5 min interval). 
 
Balance measurement 
The fluctuations of the hull are recorded and evaluated with the Sway StarÔ System (www.b2i.info). 
The Sway StarÔ is a measuring instrument that contains gyroscopes. It is attached to a belt that is 
placed around the patient's waist. The data is evaluated with the associated Sway Star Ôsoftware and 
transferred to the data sheet. This measurement is carried out after the baseline measurement and after 
the cold water bath immersion of the hand.  
 
Pain sensation 
The pain threshold is measured using a pain pressure algometer (NOD, www.to-nod.com). As soon as 
the patient reports pain, this measurement is stopped. This measurement is carried out after the baseline 
measurement and after the cold water bath immersion of the hand. 
 
Psychological measurements 
The psychological measurements (sleep disorder, altitude sickness, dyspnea, state of mind, 
drowsiness) are evaluated on the basis of written questionnaires.  
The cognitive test battery consists of 8 tasks (ANAM, US Department of Defence, Vista Life Sciences, 
USA), which are carried out on a laptop computer.  
These measurements are carried out after the baseline measurement and after the cold water bath 
immersion of the hand. 
 
9.1.3 
Measurement of secondary results 
The secondary measurement of thermal comfort and temperature perception can be measured within 1 
min.  
 
Thermal comfort and temperature perception 
This parameter is measured using a scale. The test subjects indicate their subjective temperature 
perception on a 9-point scale from -4 (very cold) to +4 (very hot). They then rate the thermal comfort 
between 0 (pleasant) and 4 (extremely unpleasant) on a 5-point scale. These measurements are carried 
out after the baseline measurement and after the cold water bath immersion of the hand. 
 
9.1.4 
Collection of further results 
No further results will be collected. 
9.1.5 
Collection of safety parameters 
Apart from the health questionnaire (including pregnancy test for female subjects), no safety parameters 
are collected. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 44 from 61 
 
9.1.5.1 
Unfavorable events  
In the event of an allergic reaction, the experiment is stopped immediately. 
9.1.5.2 
Laboratory parameters 
-  
9.1.5.3 
Vital signs 
- 
9.1.6 
Collection of data in case of early termination of studies 
For the participants, there is no disadvantage in the event of an (arbitrary) discontinuation of study 
participation and no further interventions are necessary for follow-up treatment. The data collected to 
date will be evaluated as far as possible and included in the data analysis (in accordance with Art. 9 
ClinO). 
However, if study participation was discontinued due to a reaction occurring during study participation, 
this will be recorded and reported to the sponsor investigator (head of the research laboratory), study 
management and supervisor of the study. In the event of necessary medical treatment, the report is 
sent to the business liability insurance of Thim van der Laan AG (Basler Versicherung). 
The following are recorded: 
- 
Date and time of the incident 
- 
Course of the incident 
- 
Persons involved & witnesses 
- 
Study ID (specified by the CEC) 
- 
Personal data of the person concerned (if not previously recorded) 
 
9.2 
Procedure at each visit of the test subjects 
9.2.1 
Single measurement 
The project involves multiple visits.  
 
9.2.2 
Multiple visits 
 
After contact has been made by telephone and suitability has been determined by telephone, the subject 
information and the declaration of consent are submitted for inspection and reading. If the subject agrees 
with the study conditions and criteria, he or she registers to make an appointment for the 1st contact 
day.  
The 1st contact day includes, in the order described, the; On-site explanations, signing the consent form, 
completing the health questionnaire and taking the pregnancy test for female subjects. If these points 
are passed positively, an appointment is made for the actual measurement day (2nd-5th contact day).  
 
1. On-site explanation and completion of the health questionnaire, 1st contact day 
The subjects will be comprehensively informed about the process and possible risks before they are 
confirmed to participate in the study. The declaration of consent explains to them what their rights and 
obligations are when participating and that they may withdraw from participation at any time without 
giving reasons, without incurring any disadvantages as a result. More detailed information can be found 
in chapter 2.7. In addition, a health questionnaire is filled out to identify any risks. An initial selection 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 45 from 61 
 
process of suitable test persons takes place. If the health form has been completed and no risks have 
been identified, the test subjects are summoned to the 2nd day of contact.  
 
2. Measurement, 2nd-5th day of contact 
2.1 Preparation of the subject 
The subject lies in his underwear on a treatment table for a period of 20 minutes. This is followed by the 
baseline measurement.  
 
2.2 Intervention 
The subject is then exposed to either the simulated altitude or the normobaric & normoxic situation. 
Afterwards, a step-up task of 5 minutes and a cold water bath immersion of the hand for 5 minutes is 
performed. In the terrestrial situation, the subject is measured at the time of arrival at the SAC Hut, as 
well as the following day after an overnight stay at the SAC Hut. The experimental procedure is therefore 
illustrated:   
 
Illustration of the experimental process 
 
 
2.3 Follow-up measurement 
After the step-up task and after the cold water bath immersion of the hand, follow-up measurements are 
carried out. 
After the step-up task, the perfusion of the microcirculation, the oxygen saturation of the muscles, the 
brain, the blood, the blood pressure and the heart rate, the skin temperature, the lactate and the creatine 
kinase are measured again once.  
After cold water immersion, these parameters are measured again at intervals of 5 min up to 30 min 
after hand immersion. After these parameters have been collected, the balance measurement, the pain 
sensation as well as the psychological measurements and the thermal comfort and temperature 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 46 from 61 
 
perception are measured again. 
After this measurement day is completed, the test subjects either return to the laboratory and carry out 
the same test procedure in the mountain restaurant in Valais.  
 
2.4 Conclusion and compensation 
After the last follow-up measurement and after the subject has gone through all situations, the 
examination is over for the subject. He/she will receive the amount due to him/her according to the 
advertisement. The lump sum is 100 CHF. The gondola ride, the overnight stay, the travel costs to Valais 
and the meals in the SAC hut are covered by the University of Applied Sciences and Arts Southern 
Switzerland. The total compensation is not dependent on the completion of the study. The test subjects 
will be reimbursed for the costs in any case.  
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 47 from 61 
 
10 SAFETY 
Other clinical trial with a medical device in the risk category Cat. A KlinV (Art. 20) 
 
No medication will be administered to the subjects, nor will tissue samples be taken. No invasive 
methods are used. 
 
No further security aspects are expected. 
10.1 Drug study 
 
10.1.1 Definition and assessment of (serious) adverse events and other safety related events 
- 
10.1.2 Reporting of serious adverse events (SAE) and other safety related events 
- 
10.1.3 Follow up of (Serious) Adverse Events 
- 
10.2 Medical Device Category C studies 
- 
10.2.1 Definition and Assessment of (Serious) Adverse Events and other safety related events 
- 
10.2.2 Reporting of (Serious) Adverse Events and other safety related events 
- 
10.2.3 Follow up of (Serious) Adverse Events 
- 
10.3 Medical Device Category A studies 
This project is carried out with a CE certified product. It is a study with 24 or fewer subjects. The study 
aims to gain fundamental knowledge in the field of altitude training. The study focuses on basic findings. 
The monitoring for quality assurance is carried out by Dr. Joseph Costello, who has gained numerous 
experiences and published studies in the field of extreme environmental conditions. In addition, a doctor 
is present during the measurements.  
 
10.3.1 Definition and recording of safety-relevant events 
An adverse event (ADVERSE EVENT) AE) is any unfortunate medical occurrence in a study subject 
who is exposed to a simulated or terrestrial altitude (as listed in Chapter 8.1.1) that is not necessarily 
causally related to the study process. An AE can therefore be any adverse and unintentional sign or 
symptom that can be related to the intervention product (according to Chapter 8.1.1).  
According to swissethics.ch, a serious adverse event (SAE) is classified as any unfortunate medical 
occurrence that results in death, is life-threatening, requires or prolongs hospitalization of the subject, 
results in a persistent or significant disability/inability, or is a congenital anomaly/birth defect. In our 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 48 from 61 
 
study, an SAE is not to be expected due to the amount that is being investigated.  
The equipment used in this study is used in accordance with the operating manual.  
If the examination leads to a reaction described above, this is classified as a safety-relevant event by 
the study leader. For the affected study participant, the study is completed at this time, and the data 
already collected will be processed as described in chapters 7.4 and 9.1.6. 
The subject-specific demographic data collection sheet (page 4) records:  
- 
Date and time of the incident 
- 
Course of the incident 
- 
Persons involved & witnesses 
- 
Study ID (specified by the CEC) 
- 
Personal data of the person concerned (if not previously recorded) 
 
 
10.3.2 Reporting of Safety related events 
Pursuant to Art. 37, 43 paras, 1&2 and Art. 63 Clin V. 
 
10.3.3 Notification of a security-relevant event 
A safety-related event is logged and immediately reported to the sponsor investigator (head of the 
research laboratory), study management and supervisor of the study. 
The CEC will be informed as soon as possible and appropriate changes will be made to the protocol of 
the study. Further explanations can be found in chapter 2.10. Safety and protective measures must be 
reported to the responsible CEC within two days. 
The report continues to the business liability insurance (Basler Versicherung) of Thim van der Laan AG 
in Landquart. 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 49 from 61 
 
11 STATISTICAL METHODS 
11.1 Hypotheses & Factors 
Psychophysiological changes under simulated and terrestrial altitude.  
Perfusion of skin microcirculation 
H0 
The perfusion of the skin microcirculation does not change significantly at the simulated 
altitude compared to the terrestrial altitude.  
H1 
The perfusion of the skin microcirculation changes significantly in the simulated altitude 
compared to the terrestrial altitude. 
 
Oxygen saturation of the muscles and brain 
H0 
The oxygen saturation of the muscles and the brain does not change significantly at the 
simulated altitude compared to the terrestrial altitude. 
H1 
The oxygen saturation of the muscles and the brain changes significantly in the 
simulated altitude compared to the terrestrial altitude. 
 
Oxygen saturation of the blood 
H0 
The oxygen saturation of the blood does not change significantly in the simulated 
altitude compared to the terrestrial altitude. 
H1 
The oxygen saturation of the blood changes significantly in the simulated altitude 
compared to the terrestrial altitude. 
 
Blood pressure and heart rate 
H0 
Blood pressure and heart rate do not change significantly at the simulated altitude 
compared to the terrestrial altitude. 
H1 
Blood pressure and heart rate change significantly at the simulated altitude compared 
to the terrestrial altitude. 
 
Skin temperature 
H0 
The skin temperature does not change significantly at the simulated altitude compared 
to the terrestrial altitude. 
H1 
The skin temperature changes significantly at the simulated altitude compared to the 
terrestrial altitude. 
 
Lactate and creatine kinase 
H0 
Lactate and creatine kinase do not change significantly at the simulated altitude 
compared to the terrestrial altitude. 
H1 
Lactate and creatine kinase change significantly in the simulated altitude compared to 
the terrestrial altitude. 
 
 
Equilibrium 
H0 
The equilibrium does not change significantly at the simulated altitude compared to the 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 50 from 61 
 
terrestrial altitude. 
H1 
The equilibrium changes significantly in the simulated altitude compared to the 
terrestrial altitude. 
 
Pain sensation  
H0 
The sensation of pain does not change significantly in the simulated altitude compared 
to the terrestrial altitude. 
H1 
The sensation of pain changes significantly in the simulated altitude compared to the 
terrestrial altitude. 
 
Sleep disorder 
H0 
The quality of sleep does not change significantly at the simulated altitude compared to 
the terrestrial altitude. 
H1 
The quality of sleep changes significantly in the simulated altitude compared to the 
terrestrial altitude. 
 
Symptoms of altitude sickness 
H0 
The simulated altitude does not lead to any symptoms of altitude sickness compared to 
the terrestrial altitude. 
H1 
The simulated altitude leads to symptoms of altitude sickness compared to the 
terrestrial altitude. 
 
Dyspnea 
H0 
The simulated altitude does not lead to dyspnea symptoms compared to the terrestrial 
altitude. 
H1 
The simulated altitude leads to dyspnea symptoms compared to the terrestrial altitude. 
 
State of mind 
H0 
The simulated altitude does not lead to any changes in mood compared to the terrestrial 
altitude. 
H1 
The simulated altitude leads to changes in state of mind compared to the terrestrial 
altitude. 
 
Sleepiness 
H0 
The simulated altitude does not lead to any drowsiness symptoms compared to the 
terrestrial altitude. 
H1 
The simulated altitude leads to drowsiness symptoms compared to the terrestrial 
altitude. 
 
 
Cognition 
H0 
The simulated altitude does not lead to any cognitive changes compared to the 
terrestrial altitude. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 51 from 61 
 
H1 
The simulated altitude leads to cognitive changes compared to the terrestrial altitude. 
 
Thermal comfort and temperature perception 
H0 
The thermal comfort and the temperature perception do not change significantly in the 
simulated altitude compared to the terrestrial altitude. 
H1 
Thermal comfort and temperature perception change significantly in the simulated 
altitude compared to the terrestrial altitude. 
 
 
 
A 2-factor analysis is carried out. 
Factor 1: 
Situation (simulated altitude vs. terrestrial altitude) 
Factor 2: 
Time (baseline, after step-up task, 0, 5, 10, 15, 20, 25, 30 min post-cold water immersion 
of the hand) or 
 
Time (baseline, post-cold water immersion of the hand) 
 
 
Explanations for the hypotheses:  
It has already been established that hypobaric hypoxia can have a negative impact on postural stability 
in the antero-posterior plane, compared to normobaric hypoxia. This indicates that the change in 
pressure per se can play a more important role compared to hypoxia (Degache et al. 2012). However, 
it must also be mentioned that visual acuity (the view) can also influence postural stability. Movements 
that occur and are processed unconsciously can activate muscles that play a role in postural control 
(Brandt et al. 1986). This factor is kept as low as possible during the measurement during the stay in 
the SAC hut by the test subject looking at the wall (as in the laboratory) and not into the distance (through 
a window, for example).  
Regarding oxygen saturation, measured with a pulse oximeter as in our study, the study by Savourey 
et al. 2003 and Self et al. 2011 showed that these values were lower in the hypobaric hypoxia situation 
compared to the simulated altitude. These differences were already evident after short-term exposure 
and comparable (simulated) altitude exposures to our study. For the cardiovascular differences, Faiss 
et al. 2013, Miyagawa et al. 2011 and Self et al. 2011 showed that heart rate and blood pressure 
increased after short-term exposure at terrestrial altitude, compared to the simulated altitude.  
Based on these results for oxygen saturation, heart rate and blood pressure, it stands to reason that the 
inflammation and lactate levels in the terrestrial study group are higher after submaximal exercise 
compared to the values in the simulated altitude group. However, we would like to investigate this 
hypothesis in our experiment.  
Altitude sickness symptoms, which are very often studied in this field of research, showed the following 
differences: The risk or development of altitude sickness seems to be greater at terrestrial altitude 
compared to simulated altitude (Loeppky et al. 2005, Miyagawa et al. 2011). The difference between 
terrestrial altitude and simulated altitude on sleep quality was also investigated. In both initial positions, 
oxygen transport is significantly suppressed during the sleep phase. However, the simulated height in 
this case is a continuous (during the sleep phase) situation (Berssenbrugge et al. 1983). Millet et al. 
(2012), on the other hand, described that the ventilation of the lungs, and consequently the CO2 content 
in the blood, are lower at the terrestrial altitude, compared to the simulated altitude. Poor sleep at 
terrestrial altitude could also have a negative effect on the daily state of mind as well as on drowsiness. 
Furthermore, the reduced oxygen saturation or the increased CO2 content in the arterial blood could 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 52 from 61 
 
lead to a reduction in oxygen saturation in the muscles and brain (and reduced cognitive performance) 
in the terrestrial situation. However, it must be explicitly mentioned that a direct comparison can only be 
made here if the simulated and also the terrestrial altitude are carried out in the same amount of time.   
Thermal comfort and temperature perception are largely dependent on the outside temperature. The 
room temperature in the SAC hut is therefore adapted as much as possible to the conditions of the 
laboratory in order to keep this disturbing factor as low as possible. However, the different temperature 
in the 2 scenarios could also have an impact on the perfusion of the skin's microcirculation. Furthermore, 
it was described that sympathetic tone is increased at terrestrial altitude compared to simulated altitude. 
Catecholamines, such as norepinephrine, also seem to be released more frequently at terrestrial 
altitudes (Mazzeo et al. 1994).  
The result of Noel-Jorand et al. 1996 is interesting. These authors described that the sensation of pain 
is largely dependent on the hypoxia itself and not only on the difference in air pressure. The pain 
threshold has decreased in this study and sensory discrimination has increased below terrestrial altitude. 
Hypoxia and the resulting adaptation to the lack of oxygen itself seem to be the main reason for this 
(Noel-Jorand et al. 1996).  
 
There are several mechanisms that could explain the different reactions of terrestrial and simulated 
altitude. It is obvious that the difference in air pressure and the duration of the hypoxic situation are the 
primary factors, which are different in these 2 scenarios. However, these different factors themselves 
provide information about psychophysiological effects and therefore provide the impetus for further 
discussions in this field of research. The different room temperatures could also have an influence on 
the reactions of the test subjects. In this point, we will try to keep the ambient temperature as similar as 
possible. We are aware that other factors such as contact with other people in the SAC hut, the view, 
etc. can influence the results. We will control these disruptive factors as best we can. However, it is also 
important to record these factors and bring them forward as discussion points in the study.  
11.2 Sample size 
The sample size in the literature varies. The planned number of 24 subjects is within the wide range and 
is expedient, time-wise and financially feasible for the study.  
The G*Power analysis (V.3.1.) revealed (F-test, MANOVA:repeated measures, within-between 
interaction, effect size f(V) = 0.9, alpha err prob = 0.05, Power (1-beta err prob) = 0.6, number of groups 
= 3, number of measurements = 14) a required group of 23 participants.  
 
 
11.3 Criteria for the statistical use of data in the case of incomplete data sets 
Only data from subjects who have completed the entire protocol will be included in the study. This 
ensures that all data has been collected under the same conditions and thus remains homogeneous 
and comparable. 
 
11.4 Scheduled analyses  
11.4.1 Datasets and Data Population 
Only datasets that can be used sensibly will be included in the study. Incomplete data sets that contain 
only part of the protocol are included in the analysis as far as possible. No new test subject is being 
sought to replace the missing data.  

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 53 from 61 
 
11.4.2 Primary Analysis 
The statistical data analysis will be carried out by Prof. Dr. Tom Deliens after completion of the data 
collection of the entire project. 
 
Repeated measures analysis of variance (MANOVA) 
2 factors:  
Factor 1: 
Situation (simulated altitude vs. terrestrial altitude) 
 
Factor 2: 
Time (baseline, after step-up task, 0, 5, 10, 15, 20, 25, 30 min post-cold water immersion 
of the hand)  
 
Repeated measures analysis of variance (MANOVA) 
2 factors:  
Factor 1: 
Situation (simulated altitude vs. terrestrial altitude) 
 
Factor 2: 
Time (baseline, post-cold water immersion of the hand) 
 
The significance level is set at P < 0.05, and the statistical data analysis is carried out with SPSS V. 23. 
 
 
11.4.3 Secondary Analysis 
Nonexistent. 
 
11.4.4 Interim analyses 
The data is processed after the project ends. No additional interim analyses are planned. 
 
11.4.5 Security analyses 
No security analyses are provided. 
 
11.4.6 Deviations 
Deviations from the planned statistical analysis are recorded and justified and reported to the CEC in 
the annual report. 
 
11.5 Drop-outs and missing data  
If a test subject does not complete the experiment, any data that has already been collected is destroyed 
and is not included in the final data analysis. 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 54 from 61 
 
12 QUALITY ASSURANCE AND CONTROL 
12.1 Data Archiving 
12.1.1 Forms 
Data protection and confidentiality are guaranteed and no personal data is presented or published. The 
signed declaration of consent, as well as the completed questionnaire with the other personal data and 
demographic and medical personal data are stored in the original as a study document in a locked filing 
cabinet. Only the head of the study (head of the research laboratory of the University of Applied Sciences 
and Arts Southern Switzerland, Physiotherapy Graubünden) has access (key possession) to this cabinet. 
The encryption of the identity of the test persons is not digitally recorded, i.e. surname, first name and 
date of birth are not digitally recorded in any way.  
Direct access to the personal data will continue to be allowed only to authorized persons of the CEC. 
 
12.1.2 Specification of forms 
The data collected in writing is recorded in the form listed in the enclosures and is marked as study 
data. They are therefore subject to data protection and are stored in accordance with the information 
described in chapter 12.1.1. 
 
12.1.3 Archiving of data 
The data collected will be kept for 10 years. Data protection will continue to be guaranteed. 
 
12.2 Data management  
12.2.1 Data Management System  
The raw data of the perfusion of the skin microcirculation (Laser Speckle Contrast Imager) are 
processed with the software "moorFLPI-2 full-field laser Perfusion Imager V1.1". The oxygen saturation 
of the muscles and the brain is processed with the software "moor VMS-PC v.4.2.". The i-buttons are 
read out with the i-Button MMT software. The data from the thermal imaging camera is processed with 
the "Flir Research IR max" software. The oxygen saturation values of the muscles and the brain are 
also processed with the software "moor VMS-PC v.4.2.". Lactate and creatine kinase are recorded with 
the reflotron (Roche Diagnostic, Rotkreuz, Switzerland) and transferred to a data sheet. The balance 
measurement is  recorded and evaluated with the Sway StarÔ System (www.b2i.info). Sleep disorder, 
Lake Louis altitude sickness, dyspnea, state of mind and drowsiness are recorded in writing with a 
questionnaire.  Cognition is recorded digitally on a laptop and the score is stored there. The subjective 
perceptual parameters regarding thermal comfort and temperature perception are asked orally and the 
answers are handwritten on the raw data sheet. The pain sensation is transferred to a portable PC on 
a supplied software (www.to-nod.com). 
 
12.2.2 Data security and backup 
The digital data (laser speckle contrast imager, i-button, thermal imaging camera, oxygen saturation, 
pain sensation, balance, cognition) will be anonymized and treated confidentially, access to the personal 
data will not be allowed to third parties. The digital data collected is stored solely on the institute's own 
computers and is not passed on to any external persons or transferred to other computers. Access to 
the computers of the research laboratory at the "University of Applied Sciences and Arts Southern 
Switzerland" is only granted to the head of studies and the examiners (listed in Chapter 1), as well as 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 55 from 61 
 
persons authorised by the CEC. 
 
12.2.3 Analysis and archiving 
After collection, the digital data is encrypted and stored on another external hard drive for further backup. 
This is stored in a locked filing cabinet to ensure data protection.  
 
12.2.4 Validation of electronic data  
Immediately after data collection, the quality of the data is checked and verified with the help of the 
visual representation.  
 
12.3 Monitoring  
The data collected can be viewed by authorised persons at any time (see Chapter 12.2.2) 
The study is to be monitored by the following person: 
Dr. Joseph Costello 
 
University of Portsmouth  
Department of Sport & Exercise Science  
Spinnaker Building, Cambridge Road,  
Portsmouth, Hampshire, P012ER 
 
+44 239284 5366 
joe.costello@port.ac.uk 
 
12.4 Audits and inspections  
A report on the current status of the study is given orally to the study supervisor (Dr. Joseph Costello) 
on a monthly basis. In addition, Dr. Costello will be present during the measurements. This also includes 
demonstrating and presenting results and statistical analyses.  
An annual report on the course of the study will be submitted to the CEC. Authorized persons of the 
CEC can view the data forms as well as the digital data on the institute's own computers at any time. 
Data protection is guaranteed at all times. 
 
12.5 Confidentiality and data protection 
The examiners ensure that the privacy of the participant is guaranteed. In particular, data protection and 
confidentiality are guaranteed and no personal data is presented or published. The signed declaration 
of consent, as well as the completed questionnaire with the other personal details, are kept in the original 
as a study document in a locked filing cabinet. 
The digital data will be anonymized and treated confidentially, and access to the personal data will not 
be allowed to third parties. The digital data collected is stored solely on the institute's own computers 
and is not passed on to any external persons or transferred to other computers. 
Direct access to the personal data is only allowed to authorized persons of the CEC. 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 56 from 61 
 
 
12.6 Retention of biological material and health-related data 
- 
 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 57 from 61 
 
13 PUBLICATION AND DISCLOSURE OF DATA 
The examiners ensure that the privacy of the participant is maintained. In particular, the data protection 
and confidentiality of the data are guaranteed and no personal data is presented or published nor passed 
on to outsiders and unauthorized persons. 
 
 
 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 58 from 61 
 
14 FUNDING AND SUPPORT 
14.1 
Financing 
The study is funded by the University of Applied Sciences and Arts Southern Switzerland, 
Physiotherapy Graubünden. The auditors are employed by this institute and are remunerated for their 
work on this study in accordance with their employment contracts. No further support is needed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 59 from 61 
 
15 INSURANCE 
There is a public liability insurance policy with Basler Versicherung for Thim van der Laan AG in 
Landquart, where the study is being conducted.  
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 60 from 61 
 
16 REFERENCES  
 
 
Ando, S., Hatamoto, Y., Sudo, M., Kiyonaga, A., Tanaka, H., & Higaki, Y. (2013). The effects of 
exercise under hypoxia on cognitive function. PLoS One, 8(5), E63630. 
doi:10.1371/journal.pone.0063630 
Chang, Y. K., Labban, J. D., Gapin, J. I., & Etnier, J. L. (2012). The effects of acute exercise on 
cognitive performance: a meta-analysis. Brain Res, 1453, 87-101. 
doi:10.1016/j.brainres.2012.02.068 
de Aquino Lemos, V., Antunes, H. K., dos Santos, R. V., Lira, F. S., Tufik, S., & de Mello, M. T. (2012). 
High altitude exposure impairs sleep patterns, mood, and cognitive functions. 
Psychophysiology, 49(9), 1298-1306. doi:10.1111/j.1469-8986.2012.01411.x 
Girard, O., Malatesta, D., & Millet, G.P. (2017). Walking in Hypoxia: An Efficient Treatment to Lessen 
Mechanical Constraints and Improve Health in Obese Individuals? Front Physiol, 8, 73. 
doi:10.3389/fphys.2017.00073 
Komiyama, T., Katayama, K., Sudo, M., Ishida, K., Higaki, Y., & Ando, S. (2017). Cognitive function 
during exercise under severe hypoxia. Sci Rep, 7(1), 10000. doi:10.1038/s41598-017-10332-y 
McMorris, T., Hale, B.J., Barwood, M., Costello, J., & Corbett, J. (2017). Effect of acute hypoxia on 
cognition: A systematic review and meta-regression analysis. Neurosci Biobehav Rev, 74(pt 
A), 225-232. doi:10.1016/j.neubiorev.2017.01.019 
Noel-Jorand, M. C., Bragard, D., & Plaghki, L. (1996). Pain perception under chronic high-altitude 
hypoxia. Eur J Neurosci, 8(10), 2075-2079.  
Park, H. Y., Jung, W. S., Kim, J., & Lim, K. (2019). Twelve weeks of exercise modality in hypoxia 
enhances health-related function in obese older Korean men: A randomized controlled trial. 
Geriatr Gerontol Int. doi:10.1111/ggi.13625 
Pramsohler, S., Burtscher, M., Faulhaber, M., Gatterer, H., Rausch, L., Eliasson, A., & Netzer, N. C. 
(2017). Endurance Training in Normobaric Hypoxia Imposes Less Physical Stress for Geriatric 
Rehabilitation. Front Physiol, 8, 514. doi:10.3389/fphys.2017.00514 
Smith, K. J., MacLeod, D., Willie, C. K., Lewis, N. C., Hoiland, R. L., Ikeda, K., . . . . Ainslie, P. N. 
(2014). Influence of high altitude on cerebral blood flow and fuel utilization during exercise and 
recovery. J Physiol, 592(24), 5507-5527. doi:10.1113/jphysiol.2014.281212 
Taylor, L., Watkins, S. L., Marshall, H., Dascombe, B. J., & Foster, J. (2015). The Impact of Different 
Environmental Conditions on Cognitive Function: A Focused Review. Front Physiol, 6, 372. 
doi:10.3389/fphys.2015.00372 
Tipton, M. (2012). A case for combined environmental stressor studies. Extrem Physiol Med, 1(1), 7. 
doi:10.1186/2046-7648-1-7 
 
 

 
Effect of terrestrial altitude and normobbar hypoxia - Version 02 – 01.05.2019  
Side 61 from 61 
 
 
17 APPENDIX 
1. Subject information, informed consent and demographic data (health questionnaire) 
 
2. Recruitment of test persons (advertisements) 
 
 
3. Data Collection Questionnaire Measurements (Screening Test and Measurement Data Sheet) 
 
4. Protocol Synopsis 
 
5. Employee 
 
6. CVs of all examiners