Exploratory Pilot Trial Assessing the Immediate Impact of Animal-based and Plant-based Protein Drinks on Blood Parameters
Phase: NA
Conditions: Nutrition, Healthy, Leucine Sensitivity
Sponsor: ETH Zurich

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Exploratory Pilot Trial Assessing the Immediate Impact of Animal-based and Plant-based Protein drinks on Blood 
Parameters 
Study Plant-Based Protein Drink 
Exploratory Pilot Trial Assessing the Immediate Impact of Animal-
based and Plant-based Protein drinks on Blood Parameters 
 
A national, single center, exploratory pilot study 
 
 
 
 
 
Study Type: 
Other Clinical Trial according to ClinO, Chapter 4 
 
Risk Categorisation:  
Risk category A  
 
Study Registration: 
1. ClinicalTrials.gov (not yet registered) 
2. Registration number from the FOPH portal SNCTP (Swiss 
National Clinical Trial Portal) and, if applicable, other registries and 
numbers 
 
Sponsor: 
Dr. Gommaar D’Hulst, Oberassistent 
 
Laboratory of Exercise and Health, 
 
Department of Health Sciences and Technology, 
 
ETH Zürich 
 
Schorenstrasse 16, 8603 Schwerzenbach 
dhulstg@ethz.ch 
Tel: +41 78 662 44 74 
 
Principal Investigator 
 Dr. Gommaar D’Hulst, Oberassistent 
Laboratory of Exercise and Health,  
 
 
 
 
Department of Health Sciences and Technology, 
ETH Zürich 
Schorenstrasse 16, 8603 Schwerzenbach 
dhulstg@ethz.ch  
Tel: +41 78 662 44 74 
 
 
Investigated Intervention: 
Role of a plant-based protein drink on amino acid bioavailability in 
 
 
 
 
blood 
 
Protocol ID 
 
 
Study Plant-Based Protein Drink – 2024-00151 
 
Version and Date: 
 
Version 3.0 (dated 22/04/2024) 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and the property of the sponsor. The 
information may not - in full or in part - be transmitted, reproduced, published, or disclosed to 
others than the applicable Competent Ethics Committee(s) and Regulatory Authority(ies) without 
prior written authorisation from the sponsor except to the extent necessary to obtain informed 
consent from those who will participate in the study. 
 
 

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PROTOCOL SIGNATURE FORM    
 
 
Study Title 
Exploratory Pilot Trial Assessing the Immediate Impact of 
Animal-based and Plant-based Protein drinks on Blood 
Parameters 
 
Study ID 
Study Plant-Based Protein Drink - 2024-00151 
 
The Sponsor and Principal Investigator have approved the protocol version 3.0 (dated 
22/04/2024) and confirm hereby to conduct the study according to the protocol, current version 
of the World Medical Association Declaration of Helsinki, and ICH-GCP guidelines as well as the 
local legally applicable requirements. 
 
 
 
 
Sponsor - Principal Investigator: 
 
Name: Gommaar D’Hulst 
Date: 
22-04-2024 _______________  
Signature: 
 _  
 
 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS 
2 
GLOSSARY OF ABBREVATIONS 
3 
1 STUDY SYNOPSIS 
4 
2 BACKGROUND AND RATIONALE 
6 
3 STUDY OBJECTIVES AND DESIGN 
7 
3.1 Hypothesis and primary objective 
7 
3.2 Primary endpoint 
7 
3.3 Study design 
8 
3.4. Study intervention 
8 
4 STUDY POPULATION AND STUDY PROCEDURES 
11 
4.1 Inclusion and exclusion criteria, justification of study population 
11 
4.2 Recruitment, screening and informed consent procedure 
11 
4.3 Study procedures 
12 
4.4 Withdrawal and discontinuation 
13 
5 STATISTICS AND METHODOLOGY 
14 
5.1. Statistical analysis plan and sample size calculation 
14 
5.2. Handling of missing data and drop-outs 
16 
6 REGULATORY ASPECTS AND SAFETY 
16 
6.1 Local regulations / Declaration of Helsinki 
16 
6.2 (Serious) Adverse Events and notification of safety and protective measures 
16 
6.3 (Periodic) safety reporting 
17 
6.4 Amendments 
17 
6.5 Notification and reporting upon completion, discontinuation or interruption of the study
 
17 
6.6 Insurance 
18 
7 FURTHER ASPECTS 
18 
7.1 Overall ethical considerations 
18 
7.2 Risk-benefit assessment 
19 
8 QUALITY CONTROL AND DATA PROTECTION 
19 
8.1 Quality measures 
19 
8.2 Data recording and source data 
19 
8.3 Confidentiality and coding 
20 
8.4 Retention and destruction of study data and biological material 
20 
9  MONITORING AND REGISTRATION 
21 
10. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
21 
11. REFERENCES 
21 
 
 

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GLOSSARY OF ABBREVATIONS 
 
AE 
 
Adverse Event 
ASR 
 
Annual Safety Repot 
BASEC 
 
Business Administration System for Ethical Committees 
CRF 
 
Case Report Form 
CTCAE 
 
Common Terminology Criteria for Adverse Events 
FADP 
 
Federal Act on Data Protection (in German: DSG, in French: LPD, in Italian: 
LPD) 
eCRF 
 
electronic Case Report Form 
FOPH 
 
Federal Office of Public Health 
GCP 
 
Good Clinical Practice 
HRA 
 
Human Research Act (in German: HFG, in French: LRH, in Italian: LRUm) 
ICH 
 
International Conference on Harmonisation  
ClinO 
 
Ordinance on Clinical Trials in Human Research (in German: KlinV, in 
French: OClin, in Italian: OSRUm) 
SAE 
 
Serious Adverse Event 
HPLC  
 
High-Performance Liquid Chromatography 
FSMP 
 
Food for Special Medical Purposes 
REDCap system 
Web-based Electronic Data Capture system 
 
 
 

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1 
STUDY SYNOPSIS 
Sponsor / 
Sponsor-
Investigator 
Dr. Gommaar D’Hulst 
Laboratory of Exercise and Health 
Department of Health Sciences and Technology 
ETH Zürich 
Schorenstrasse 16, 8603 Schwerzenbach 
dhulstg@ethz.ch 
+41 78 662 44 74 
Study Title 
Exploratory Pilot Trial Assessing the Immediate Impact of Animal-based and Plant-based 
Protein drinks on Blood Parameters 
Short Title / 
Study ID 
Study Plant-Based Protein Drink 
Protocol Version 
and Date 
Version 3.0 (dated 22/04/2024) 
Study 
Registration 
ClinicalTrials.gov - TBD 
Study Category 
and Rationale 
This clinical study qualifies as Category A because it involves only minimal risks to the 
participants, primarily associated with routine blood sampling, a standard and non-invasive 
procedure. The interventions include consumption of already marketed and food-grade 
products, thus not introducing novel or unknown risks. Additionally, the study's objective is to 
assess nutritional properties rather than to explore therapeutic effects, aligning it with the 
criteria for low-risk, non-therapeutic research typically categorized under Category A.  
Background and 
Rationale  
Addressing environmental concerns, our team has developed a unique beverage from plant-
based proteins, aimed at improving bioavailability. This is crucial, as low bioavailability in 
plant proteins can lead to malnutrition, particularly in the elderly. With an increasing demand 
for plant-based options among the aging population, our study will compare this new drink's 
nutritional and amino acid bioavailability with traditional animal-based products. Our goal is to 
provide a sustainable choice that maintains the nutritional advantages typically found in 
animal proteins. 
Risk / Benefit 
Assessment 
Risks: 
- 
Minor discomfort and risks associated with blood sampling 
- 
Potential allergic reactions to ingredients in the drinks 
Benefits: 
- 
Advancing knowledge in plant-based nutrition. 
- 
Potential development of a nutritionally equivalent plant-based alternative to animal 
proteins. 
- 
Contribution to sustainable food practices. 
Objective(s) 
The objective of the study is to quantitatively assess the bioavailability of leucine in the blood 
following the consumption of a novel animal -and plant-based protein drink. This assessment 
will be compared to the bioavailability observed after consuming a commercially available 
animal-based protein drink. Leucine is the rate-limiting amino acid that drives protein 
synthesis in muscle and is associated with preservation of muscle mass during aging and 
inactivity. 
the study aims to determine whether the plant-based drink can match or exceed the 
bioavailability of amino acids typically seen in animal protein sources, thereby offering a 
viable nutritional alternative for those seeking plant-based diets. 
Endpoint(s) 
Leucine bioavailability in blood (Area Under the Curve) 
Study Design 
 
Exploratory, single center, randomized, single-blinded, cross-over controlled pilot study with 
three arms  
Statistical 
Considerations 
Repeated-measures ANOVA, sample size calculation is on the expected effect size based 
on previous literature, the desired level of statistical power (80%), and the significance level 
(0.05). 
Inclusion- / 
Exclusion 
Criteria 
Inclusion criteria: male and female, 18-40 years, signed written informed consent 
Exclusion criteria: smoking history, cardiovascular diseases , BMI > 35 kg/m2, allergies: Soy, 
Peas, Milk, Lactose, Fructose 

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Number of 
Participants with 
Rationale 
The power analysis was informed by a precedent human study (PMID: 36615694) that 
established average leucine AUC values to be 20,000 (with a standard deviation of 2,000) for 
plant-based drinks and 28,000 (with an updated standard deviation of 6,100) for animal-
based drinks (whey). The mean difference between plant and animal drinks was identified as 
8,000 units from this research. This study was performed in men and women, with no 
differences in leucine AUC between genders. Adjusting for the crossover design, the power 
analysis indicated that approximately 9-10 participants would suffice to achieve the desired 
statistical power of 0.80 and an alpha level of 0.05. This sample size estimation directly 
reflects the enhanced efficiency and reduced variability afforded by the crossover design, as 
compared to a traditional parallel-group RCT, in discerning significant differences in leucine 
AUC among the dietary interventions examined. We will recruit 12 participants to account for 
dropouts (10-20%). Calculations have been done in python 
Study 
Intervention 
Participants will be administered three different drinks in a randomized crossover order. 
These drinks are: 
- 
Animal-based A: A commercially available high protein drink, based on animal 
proteins (Fresubin Protein Energy). 
- 
Animal-based B: A homemade drink containing animal-based proteins, using a 
specific animal-based protein isolate mix. 
- 
Plant-based A: A homemade drink containing plant-based proteins, formulated to 
have the same macronutrient content as the animal-based drinks. 
Participants will arrive fasted at the lab. After a 60 min seated rest, a baseline blood sample 
will be taken 30 minutes prior to consuming the drink. After consuming the assigned drink, a 
blood sample will be collected 30, 60 and 90 minutes later, to determine leucine appearance 
(AUC). This procedure will be repeated three times, each with a different drink, with 5-7 days 
washout in between. The primary measure of the study is the leucine content in the blood, 
determined using High-Performance Liquid Chromatography (HPLC). 
Control 
Intervention 
Each participant acts as his/her own control. The usual inter-subject variability is minimized 
by the cross-over design as each participant is used as their internal control as each drink is 
tested in every participant.   
Study 
procedures 
- 
Recruitment and Screening (Month 1): Recruitment and screening aim to enroll 14 
participants within one month. 
- 
Lab Visits (Months 2-3): Participants undergo three lab visits of about 4 hours at 
Laboratory Exercise and Health, ETH Zurich. Patients arrive fasted at the lab. Each 
visit includes a 60-minute seated rest, followed by one blood sample collection 
before and two blood sample collections after drink consumption. Samples are 
processed and stored at -80°C for further analysis. 
- 
Analysis (Month 4): High-Performance Liquid Chromatography (HPLC) used to 
measure leucine content in blood samples, assessing protein bioavailability. 
Study Duration 
and Schedule 
Planned 06/2024 of First-Participant-In 
Planned 09/2024 of Last-Participant-Out 
Investigator(s) 
Dr. Gommaar D’Hulst 
Laboratory of Exercise and Health 
Department of Health Sciences and Technology 
ETH Zürich 
Schorenstrasse 16, 8603 Schwerzenbach 
dhulstg@ethz.ch  
Tel: +41 78 662 44 74 
Study Center(s) 
Laboratory Exercise and Health, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach 
Data privacy 
Privacy of data is guaranteed. Unique identifiers will be assigned to participants. This means 
that the data collected, analyzed, and reported cannot be traced back to individual 
participants. Secure Data Storage: All data, both physical and electronic, is stored in secure, 
access-controlled environments. All data is stored in an encrypted digital system (REDCap).  
Biological material in this study is not identified by participant name but by a unique 
participant number. Biological material is appropriately stored in a restricted area only 
accessible to the authorized personnel. 

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Access to data will be restricted to authorized personnel, and appropriate encryption 
techniques will be applied to protect participant confidentiality. 
Ethical 
consideration 
The scientific value of this study lies in its evaluation of the bioavailability of leucine from a 
plant-based protein drink as compared to an animal-based one. This research is particularly 
relevant in the field of nutrition science, as it addresses the challenge of developing 
sustainable, plant-based protein sources that are nutritionally comparable to animal proteins. 
The study contributes significantly to the understanding of how plant-based diets can be 
optimized for enhanced human health, aligning with sustainability objectives in food 
production. Currently, there is a gap in knowledge regarding how a beverage specifically 
optimized for amino acid bioavailability, particularly leucine, stacks up against traditional 
animal-based protein drinks. This study aims to fill that gap, providing valuable insights into 
the potential of plant-based proteins in meeting nutritional needs. 
 
Justification of Methodology: High-Performance Liquid Chromatography (HPLC) has been 
selected for its accuracy in measuring specific amino acids, such as leucine, in blood samples. 
This method is known for its precision, making it ideal for quantifying amino acid levels 
accurately. The use of a randomized crossover design in this study ensures that each 
participant serves as their own control. This approach significantly enhances the reliability of 
the results, as it reduces the variability that can arise from individual differences between 
participants. Standard procedures like fasting and routine blood sampling are incorporated to 
accurately assess the bioavailability of nutrients. Fasting ensures that the baseline levels of 
amino acids are consistent across participants, while routine blood sampling allows for the 
tracking of changes in leucine levels over time following the consumption of the test drinks. 
 
The balance of risk and benefits for the participants, and by extension, for society, is carefully 
considered in this study. Participation is voluntary, and participants are expected to visit the 
lab three times over a short period of three weeks, each visit lasting approximately 4 hours. 
They will be compensated CHF 100 for their time and expenses. The study involves minimal 
invasive procedures, including the consumption of an animal- or plant-based drink and blood 
sampling. Considering these aspects, the study is structured to maintain a fair balance 
between risks and benefits, ensuring ethical integrity and participant safety while aiming to 
contribute valuable insights to the field of nutrition science.  
GCP Statement 
This study will be conducted in compliance with the protocol, the current version of the 
Declaration of Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and 
regulatory requirements. 
 
 
2 
BACKGROUND AND RATIONALE  
Sufficient protein is very important for health, living well, and living longer (West et al., 2012). It is 
not just about how much protein a person eats, but also about its quality and where it is sourced. 
Proteins from animals are usually better because they are high in leucine and are easy to digest. 
However, they are not as good for the environment because farming animals on a large scale 
uses a lot of energy and water, and leads to more greenhouse gas emissions (Godfray et al., 
2018). Addressing these environmental concerns, our team has developed a unique beverage 
from plant-based proteins, aimed at improving amino acid bioavailability. This is crucial, as low 
overall protein intake, combined with decreased bioavailability in plant proteins can lead to 
malnutrition, particularly in the elderly (Hida et al., 2014; van Vliet et al., 2015; Villet et al., 2005). 
Malnutrition in elderly is a huge societal burden costing Switzerland alone up to 500 Mio CHF per 
year due to longer hospitalization, increased risk of falling and muscle wasting (Frei, 2006). With 
an increasing demand for plant-based options among the aging population, our study will 
compare this new drink's nutritional and amino acid bioavailability with traditional animal-based 
products. Our goal is to provide a sustainable choice that maintains the nutritional advantages 
typically found in animal proteins. 

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The risk level of this study is considered low (A) because it only involves minor procedures like 
drawing blood and drinking a beverage that is safe for consumption. We think the advantages of 
this research far outweigh the slightly invasive methods, as it will significantly increase knowledge 
and interest for the benefit of society related to the effectiveness of plant-based drinks in tackling 
sarcopenia. 
 
Scientific Value of the Study: 
The study aims to evaluate the bioavailability of leucine from a plant-based protein drink 
compared to an animal-based protein drink (D’Hulst et al., 2021). Bioavailability is defined here 
as the appearance of amino acids in the blood plasma after consuming a protein-rich drink (Beal 
& Ortenzi, 2022). This has significant implications in nutrition science, especially for developing 
sustainable, plant-based protein sources that can match the nutritional value of animal proteins. 
Adequate levels of leucine in the blood and muscles are connected to increased muscle protein 
synthesis (D’Hulst et al., 2022), which over time helps in maintaining and growing muscles 
(Joanisse et al., 2020). Plant-based diets often have less leucine and lower bioavailability, which 
could lead to faster muscle loss if the protein content is not increased to levels usually found in 
animal-based diets (van Vliet et al., 2015). This project aims to explore how plant-based diets can 
be improved for better human health and to meet sustainability goals in food production. We have 
developed a drink that can be consumed by both older and younger people, containing a special 
blend of plant proteins that, according to our initial data, improves bioavailability and leucine 
absorption. However, it is still not clear how this optimized beverage compares to animal-based 
protein drinks, particularly in terms of leucine content. Initially, we aim to conduct a pilot study 
where younger (<40 y/o) participants are tested. Using that data and expertise, we aim to conduct 
a larger RCT in older patients once this pilot is finished. The purpose of this pilot study is to refine 
our experimental methods, choose the best drinks for testing in a larger trial involving older 
patients, and determine the right number of participants. We have set the upper age limit at 40 
years to ensure that age-related factors don not interfere with our results on protein absorption. 
3 
STUDY OBJECTIVES AND DESIGN  
3.1 Hypothesis and primary objective 
Hypothesis:  
We hypothesize that our plant-based, food-grade drink will result in blood leucine levels reaching 
up to 90% of those achieved by consuming an existing animal-based drink (Fresubin by Fresenius 
Kabi) or a comparable self-formulated animal-based drink. The self-formulated drink will contain 
the same ingredients as the plant-based one, except that the plant-based proteins will be replaced 
with animal-based whey protein.Primary objective: The objective of the study is to quantitatively 
assess the bioavailability of leucine in the blood following the consumption of a novel, but fully 
food-grade plant-based protein drink. This assessment will be compared to the bioavailability 
observed after consuming a animal-based protein drinks (commercial and self-formulated). By 
measuring leucine levels in the blood using High-Performance Liquid Chromatography (HPLC), 
the study aims to determine whether the plant-based drink can match or exceed the bioavailability 
of amino acids typically seen in animal protein sources, thereby offering a viable nutritional 
alternative for those seeking plant-based diets. 
3.2 Primary endpoint 
Primary endpoint: Leucine bioavailability in blood (HPLC), assessed by Area Under the Curve 
(AUC). We specifically chose leucine as this is the primary amino acids that triggers the synthesis 
of new proteins in the muscle via mechanistic target of rapamycin (D’Hulst et al., 2020). Typically, 
when a protein source is rich in leucine and consumption of it leads to a high level of leucine in 
the blood after consumption, like with whey protein, it promotes more muscle protein synthesis 
compared to a drink based on a single plant protein source, such as soy. Therefore, with our new 

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drink, we aim to optimize the appearance of leucine in the blood, which is a good indicator of 
protein synthesis in resting muscles. Age does affect bioavailability and protein synthesis 
(Schiaffino et al., 2013), hence, for this pilot trial we opt to study young, healthy individuals, males 
and females. 
3.3 Study design  
This will be an exploratory, single center, randomized, single-blinded, cross-over controlled pilot 
study with three arms: animal-based A, animal-based B, plant-based A. This study is designated 
as a 'pilot' because its objective is to generate scientifically valid data that can be leveraged for a 
more extensive future study focusing on older individuals experiencing malnutrition. 
This trial design has the highest scientific validity as each participant will serve as their own control, 
and randomization determines the order in which the participants receive the drinks. The usual 
inter-subject variability is minimized by the cross-over design as each participant is used as their 
internal control as each drink is tested in every participant.   
This study is a preliminary step (pilot) where we will examine how well leucine from various 
protein drinks is absorbed by people younger than 40 years old, as detailed in section 3.4. 
The findings from this initial study will help us design and carry out a more extensive, main 
study with older participants.  
3.4. Study intervention 
Participants will be administered three different drinks in a randomized crossover order. These 
drinks are: 
- 
Animal-based A: A commercially available high protein drink, based on animal proteins 
(Fresubin Protein Energy Fresenius Kabi). 
- 
Animal-based B: A homemade drink containing animal-based proteins, using a specific 
animal-based protein isolate mix. 
- 
Plant-based A: A homemade drink containing plant-based proteins, formulated to have 
the same macronutrient content as the animal-based drinks. 
** all drinks will have the same total protein content, and all participants will receive the same total 
amount of proteins. 
 
Composition of drinks: 
 
Animal Drink A:  
https://www.fresenius-kabi.com/de-ch/produkte/fresubin-protein-energy-drink 
https://www.fresubin.com/sites/default/files/2020-
02/Productsheet_Fresubin%20Protein%20Energy_2019.pdf 
 
 

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Animal Drink B 
Reference Unit 
Unit Content per 100 ml 
Energy, Calories kcal 
150 
Fat 
g 
6.6 
Carbohydrates 
g 
12.7 
- of which sugars g 
8.8 
Protein 
g 
10 

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- of which leucine g 
1 
 
 
 
Plant Drink A 
 
 
Reference Unit 
Unit Content per 100 ml 
Energy, Calories kcal 
150 
Fat 
g 
6.9 
Carbohydrates 
g 
11.7 
- of which sugars g 
8.4 
Protein 
g 
10 
- of which leucine g 
0.8 
 
 
Vitamin and mineral content of drinks (same for Animal Drink B and Plant Drink A): 
Nutrient 
Unit Content per 100 ml 
Vitamin A (μg-RE) 
μg 
213 
Sodium (mg) 
mg 
50 
Vitamin D (μg) 
μg 
2.5 
Potassium (mg) 
mg 
130 
Vitamin E (mg α-TE) 
mg 
3.75 
Chloride (mg) 
mg 
73 
Vitamin K (μg) 
μg 
21 
Calcium (mg) 
mg 
205 
Vitamin C (mg) 
mg 
18.8 
Phosphorus (mg) 
mg 
120 
Thiamin (Vitamin B1) (mg) 
mg 
0.3 
Magnesium (mg) 
mg 
28 
Riboflavin (Vitamin B2) (mg) mg 
0.4 
Iron (mg) 
mg 
2.5 
Niacin (Vitamin PP) (mg NE) mg 
1.5 
Zinc (mg) 
mg 
2 
Vitamin B6 (mg) 
mg 
0.43 
Copper (mg) 
mg 
0.375 
Folic Acid (μg) 
μg 
62.5 
Manganese (mg) 
mg 
0.5 
Vitamin B12 (μg) 
μg 
0.73 
Selenium (μg) 
μg 
13.5 
Biotin (μg) 
μg 
9.4 
Chromium (μg) 
μg 
12.5 
Pantothenic Acid (mg) 
mg 
1.5 
Molybdenum (μg) 
μg 
18.8 
Iodine (μg) 
μg 
37.5 
Fluoride (mg) 
mg 
0.25 
 

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Drinks will be manufactured in a Food Grade Laboratory, LFO, ETH Zurich using standard mixing 
and homogenization procedures. Drinks will be sterilized using pasteurization (heating to 80 °C 
for 1 min. Exact composition of the drinks will be verified by Eurofins Scientific 
(https://www.eurofins.com/) 
Participants will arrive fasted at the lab. After a 60 min seated rest, a baseline blood sample will 
be taken 30 minutes prior to consuming the drink. After consuming the assigned drink, a second, 
third and fourth blood sample will be collected 30, 60 and 90 minutes later, to determine leucine 
appearance (Area Under the Curve, AUC). This procedure will be repeated three times, each with 
a different drink, with 5-7 days washout in between. The primary measure of the study is the 
leucine content in the blood, determined using High-Performance Liquid Chromatography 
(HPLC), to assess the bioavailability of the proteins in the drinks. 
We are testing two kinds of animal-based protein drinks and one plant-based protein drink. The 
reason for this is we are creating alternatives to the nutritional drinks currently sold by companies 
like Nestlé and Fresubin (FSMP products). We have made a drink using whey (which comes from 
animals) and another using a combination of pea and rice (which are plants), ensuring both have 
the same mix of nutrients as the ones you can buy now. We want to see if our drinks are better 
at delivering leucine to the body compared to the existing products.  
 
4 
STUDY POPULATION AND STUDY PROCEDURES 
4.1 Inclusion and exclusion criteria, justification of study population 
A total of 12 healthy volunteers will be recruited for this study of which 6 males and 6 females. 
 
Inclusion criteria 
• 
Gender: male and female 
• 
Age: 18-40 years 
• 
Signed written informed consent 
 
Exclusion criteria 
• 
Smoking history 
• 
Cardiovascular diseases   
• 
BMI > 35 kg/m2 
• 
Caffeine consumption < 1 day before the study participation 
• 
Allergies: Soy, Peas, Milk, Lactose, Fructose 
• 
High intensity exercise <2 days before study participation 
 
4.2 Recruitment, screening and informed consent procedure 
The participant recruitment will occur using advertisements and social media within the Zurich 
area. The investigators will explain to each participant the nature of the study, its purpose, the 
procedures involved, the expected duration, the potential risks and benefits and any discomfort it 
may entail. Each participant will be informed that the participation in the study is voluntary and 
that he or she may withdraw from the study at any time and that withdrawal of consent will not 
have any consequences. All participants for the study will be provided a participant information 
sheet and a consent form describing the study and providing sufficient information for participant 
to make an informed decision about their participation in the study. One week time will be given 
to the participant to decide whether to participate or not. The formal consent of a participant, using 
the approved consent form, will be obtained before the participant is submitted to any study 
procedure.   

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The consent form will be signed and dated by the investigator or his designee at the same time 
as the participant sign. A copy of the signed informed consent will be given to the study participant. 
The consent form will be retained as part of the study records. After potential participants have 
given their informed consent, the project leader will accurately verify again the inclusion and 
exclusion criteria of the study. If all inclusion and exclusion criteria are fulfilled, participants will be 
included in the study. Study participants will receive CHF 100 for their participation into the study, 
after completion of the third experimental arm. 
4.3 Study procedures 
 
Overall Project Duration: 
The project encompasses a total duration of four months, inclusive of the recruitment period and 
participation for each study subject. All the study procedures are summarized with a time 
schedule in Table 1. 
 
Sequence of Planned Procedures: 
1. Recruitment and screening (Month 1) 
Recruitment and screening are projected to span one month, with the goal of enrolling 14 study 
participants. 
• 
Participants will be recruited through advertisements and social media. 
• 
Screening procedures will ensure eligibility criteria are met. 
 
2. Lab Visits (Months 2-3): 
Participants will undergo three lab visits at Laboratory Exercise and Health, D-HEST, 
Schorenstrasse 16, 8603 Schwerzenbach 
• 
Participants will arrive fasted at the lab (no food and beverages starting at midnight) 
• 
Each lab visit involves a 60-minute seated rest, followed by blood sample collection 
minutes before consuming the drink and 30, 60 and 90 minutes after consuming the 
assigned drink (see point 3. below). 
• 
Three following three different drinks will be administered in a randomized order, with 5-7 
days washout between visits: 
o Animal-based A: A commercially available high protein drink, based on animal 
proteins (Fresubin Protein Energy). 
o Animal-based B: A homemade drink containing animal-based proteins 
o Plant-based B: A homemade drink containing plant-based proteins, formulated to 
have the same macronutrient content as the animal-based drinks. 
 
• All ingredients of the drink are food grade and prepared at a food-grade level (Laboratory 
of Sustainable Food Processing, ETH Zurich). Exact ingredients are: Plant protein isolates 
(pea, rice, hemp, pumpkin), Animal-based isolates (whey) water, maltodextrin, fruit puree 
(raspberry). All ingredients are commercially available. 
 
• Total volume of the drink will range from 250ml to 400ml depending on the bodyweight of 
the participant 
 
• 
During the first visit there will be also a short assessment of participants’ characteristics 
(i.e. sociodemographic data and self-reported physical activity level). The following 
characteristics will be collected by the project leader/study personnel, inserted in a 
dedicated electronic Case Report Form (eCRF) within a web-based Electronic Data 
Capture (REDCap) system. 
 

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Procedure routine blood sample collection  
 
Blood Sample Collection: Venous blood samples will be taken by a registered nurse during the 3 
lab visits at four time points - 30 minutes before consumption of the drink, 30 minutes, 60 minutes 
and 90 minutes after the consumption of each drink. Blood will be drawn from the participant using 
a catheter. The selected vein, in the arm, will be disinfected with an alcohol swab. A catheter will 
then be inserted into the vein, and blood will be collected into appropriate tubes. After the blood 
collection, the catheter will be removed, and pressure will be applied to the puncture site with 
gauze or a cotton ball. The site will then be covered with an adhesive bandage or tape. All 
procedures will be performed following standard infection control protocols.  
Throughout the whole protocol each day, approximately 30 ml of blood will be drawn (3 x 10 ml). 
Processing and Storage: Blood will be centrifuged to separate plasma, and the samples are 
stored in -80 until further analysis. 
 
3. Analysis (Month 4): 
High-Performance Liquid Chromatography (HPLC): The primary measure of the study is the 
leucine content in the blood. This method ensures precise assessment of protein bioavailability 
in the administered drinks. This is a method used for separating, identifying, and quantifying each 
component in a mixture. In our study, HPLC will be used to analyze the leucine content in blood 
samples. It is a precise method that allows for the effective measurement of specific amino acids 
like leucine. We will only measure leucine from the blood. 
 
Expected Biases and Mitigation Measures: 
We acknowledge potential biases in the study, such as order effects and participant compliance. 
To mitigate these biases:  
• 
Randomized order of drink administration minimizes order effects  
• 
Drink administration is conducted in a single-blinded manner. 
• 
Strict adherence to the washout period reduces carryover effects. 
• 
Participants will receive thorough instructions and reminders to enhance compliance. 
 
Table 1. Timeline of study procedures 
Time (Months) 
Month 1 
Month 2-3 
Month 4 
Visit 
Information Lab visit 1 
Lab visit 2 
Lab visit 3 
Analysis 
Recruitment and 
screening 
+ 
 
 
 
 
Written consent 
+ 
 
 
 
 
Check inclusion-/ 
exclusion criteria 
+ 
 
 
 
 
Participant 
Characteristics  
 
+ 
 
 
 
Questionnaire 
 
+ 
 
 
 
Sampling 
 
+ 
+ 
+ 
 
Assessment of 
primary endpoints 
 
 
 
 
+ 
 
4.4 Withdrawal and discontinuation 
Participants will discontinue from the study in case of withdrawal of their informed consent or 
premature participant withdrawal (i.e. before Lab visit 3). In this case, the collected study-related 

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data and blood samples will be destroyed. After data analysis, study-related data will be 
anonymized, except when the concerned participant will expressly renounce to this right. 
5 
STATISTICS AND METHODOLOGY 
5.1. Statistical analysis plan and sample size calculation 
Our null hypothesis posits that the consumption of our plant-based, food-grade beverage does 
not result in a statistically significant difference in blood leucine levels compared to the 
consumption of an animal-based drink currently available in the market (Resource, Nestlé). 
Specifically, we anticipate that the leucine level attained by our plant-based drink does not exceed 
90% of the level achieved by the animal-based alternative.  
 
The study employs a crossover randomized controlled trial (RCT) design to investigate 
differences in leucine absorption, as measured by Area Under the Curve (AUC), following the 
consumption of animal drink A, animal drink B, and plant drink C. Each participant serves as their 
own control, receiving each of the three treatments in a randomized sequence over separate 
periods. 
 
Detailed statistical plan: 
1. Test for Normality 
The Shapiro-Wilk test, with a significance level (α) set at 0.05, will assess the normality of the 
distribution of our variables. This test helps determine the appropriateness of parametric tests 
such as ANOVA for our data. 
 
2. ANOVA 
Our analysis will feature an ANOVA to examine the main effects of each drink (factors A, B, and 
C) and their interaction effects. This involves calculating sums of squares, degrees of freedom, 
mean squares, and F-statistics to understand each factor's impact and the interactions among 
them. We will interpret these effects, reporting the overall F-statistic and its associated p-value, 
and use a significance level to declare statistical significance. 
 
3. Post-hoc Comparisons 
Should the ANOVA indicate significant effects, post-hoc comparisons using methods such as 
Tukey's HSD or Bonferroni correction will pinpoint specific group differences. We will report 
adjusted p-values and confidence intervals for each comparison, providing detailed insight into 
the drinks' effects. 
 
4. Effect Size 
To test the practical significance of our findings, we will calculate effect sizes, such as beta-
squared or partial beta-squared, for each factor and interaction. Power analysis 
The power analysis was informed by a precedent human study (PMID: 36615694) that 
established average leucine AUC values to be 20,000 (with a standard deviation of 2,000) for 
plant-based drinks and 28,000 (with an updated standard deviation of 6,100) for animal-based 
drinks (whey). The mean difference between plant and animal drinks was identified as 8,000 units 
from this research. This study was performed in men and women, with no differences in leucine 
AUC between genders. 
 
Given the crossover design's ability to significantly reduce between-subject variability by 
comparing treatments within the same individual, a within-subject correlation coefficient of 0.5 

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was assumed for the analysis. This assumption facilitated a more precise estimation of the 
required sample size, accounting for the intrinsic efficiency of the crossover approach in detecting 
treatment effects. 
 
Adjusting for the crossover design, the power analysis indicated that approximately 9-10 
participants would suffice to achieve the desired statistical power of 0.80 and an alpha level of 
0.05. This sample size estimation directly reflects the enhanced efficiency and reduced variability 
afforded by the crossover design, as compared to a traditional parallel-group RCT, in discerning 
significant differences in leucine AUC among the dietary interventions examined. 
 
We will recruit 12 participants to account for dropouts (10-20%). 
 
CODE used in Python to calculate the n number: 
from math import sqrt 
from statsmodels.stats.power import FTestAnovaPower 
 
# Updated standard deviation for the animal-based group 
sd_animal_updated = 6100 
 
# Given mean difference between plant and animal drinks 
mean_diff = 8000 
 
# Recalculate the effect size with the updated standard deviation 
effect_size_updated = mean_diff / sd_animal_updated 
 
# Calculate Cohen's f squared from the updated effect size (for ANOVA) 
cohens_f_squared_updated = effect_size_updated**2 / (1 + effect_size_updated**2) 
cohens_f_updated = sqrt(cohens_f_squared_updated) 
 
# Setup for ANOVA power analysis 
power_analysis = FTestAnovaPower() 
 
# Number of groups (treatments) 
num_groups = 3 
 
# Desired power and alpha level 
power = 0.8 
alpha = 0.05 
 
# Calculate required sample size per group with the updated effect size 
sample_size_per_group_updated = power_analysis.solve_power(effect_size=cohens_f_updated,  
                                                           alpha=alpha,  
                                                           power=power,  
                                                           k_groups=num_groups) 
 
# Assumption for typical within-subject correlation in crossover dietary intervention studies 
within_subject_correlation = 0.5 
 
# Adjusting the sample size estimate for the crossover design 
n_parallel = sample_size_per_group_updated 
k = 3 
r = within_subject_correlation 
 
# Adjusted sample size for crossover design 
n_crossover = n_parallel / (1 + (k - 1) * r) 

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print(f"Adjusted sample size for crossover design: {n_crossover}") 
 
5.2. Handling of missing data and drop-outs 
Missing data will be handled by complete case analysis. If the participant withdraws prematurely 
or drops out (i.e. before Lab visit 3), they will be replaced by recruitment of new subjects to ensure 
an adequate number of participants in the study. 
 
6 
REGULATORY ASPECTS AND SAFETY 
6.1 Local regulations / Declaration of Helsinki 
This study is conducted in compliance with the protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and regulatory 
requirements.  
6.2 (Serious) Adverse Events and notification of safety and protective measures 
An Adverse Event (AE) is any untoward medical occurrence in a patient or a clinical investigation 
subject which does not necessarily have a causal relationship with the trial procedure. An AE can 
therefore be any unfavourable or unintended finding, symptom, or disease temporally associated 
with a trial procedure, whether or not related to it. 
 
A Serious Adverse Event (SAE) (ClinO, Art. 63) is any untoward medical occurrence that 
- 
Results in death or is life-threatening, 
- 
Requires in-patient hospitalisation or prolongation of existing hospitalisation, 
- 
Results in persistent or significant disability or incapacity, or 
- 
Causes a congenital anomaly or birth defect  
 
Both Investigator and Sponsor-Investigator make a causality assessment of the event to the trial 
intervention, (see table below based on the terms given in ICH E2A guidelines). Any event 
assessed as possibly, probably or definitely related is classified as related to the trial intervention. 
 
Relationship 
Description 
Definitely 
Temporal relationship 
Improvement after dechallenge* 
Recurrence after rechallenge 
(or other proof of drug cause) 
Probably 
Temporal relationship 
Improvement after dechallenge 
No other cause evident 
Possibly 
Temporal relationship 
Other cause possible 
Unlikely 
Any assessable reaction that does not fulfil the above conditions 
Not related 
Causal relationship can be ruled out 
*Improvement after dechallenge only taken into consideration, if applicable to reaction 

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Both Investigator and Sponsor-Investigator make a severity assessment of the event as mild, 
moderate or severe. Mild means the complication is tolerable, moderate means it interferes with 
daily activities and severe means it renders daily activities impossible.  
 
Reporting of SAEs (see ClinO, Art. 63) 
All SAEs are documented and reported immediately (within a maximum of 24 hours) to the 
Sponsor-Investigator of the study. 
If it cannot be excluded that the SAE occurring in Switzerland is attributable to the intervention 
under investigation, the Investigator reports it to the Ethics Committee via BASEC within 15 days. 
 
Follow up of (Serious) Adverse Events 
Describe the follow up procedures of participants terminating the study with reported ongoing 
(S)AEs until resolution or stabilisation.  
 
Notification of safety and protective measures (see ClinO, Art 62, b) 
If immediate safety and protective measures have to be taken during the conduct of the study, 
the investigator notifies the Ethics committee of these measures, and of the circumstances 
necessitating them, within 7 days. 
6.3 (Periodic) safety reporting 
An annual safety report (ASR) is submitted once a year to the local Ethics Committee by the 
Investigator (ClinO, Art. 43 Abs 1). 
6.4 Amendments 
Substantial changes to the study setup and study organization, the protocol and relevant study 
documents are submitted to the Ethics Committee for approval before implementation. Under 
emergency circumstances, deviations from the protocol to protect the rights, safety and well-being 
of human subjects may proceed without prior approval of the Ethics Committee. Such deviations 
shall be documented and reported to the Ethics Committee as soon as possible. Substantial 
amendments are changes that affect the safety, health, rights and obligations of participants, 
changes in the protocol that affect study objective(s) or central research topic, changes of study 
site(s) or of study leader and sponsor (ClinO, Art. 29). A list of substantial changes is also 
available on www.swissethics.ch. A list of all non-substantial amendments will be submitted once 
a year to the competent EC together with the ASR. 
6.5 Notification and reporting upon completion, discontinuation or interruption of the 
study 
Upon regular study completion, the Ethics Committee is notified via BASEC within 90 days (ClinO, 
Art. 38). The Sponsor-Investigator may terminate the study prematurely according to certain 
circumstances, e.g. 
- 
Ethical concerns, 
- 
Insufficient participant recruitment, 
- 
When the safety of the participants is doubtful or at risk (e.g. when the benefit-risk 
assessment is no longer positive), 
- 
Early evidence of harm or benefit of the experimental intervention 
Upon premature study termination or study interruption, the Ethics Committee is notified via 
BASEC within 15 days (ClinO, Art. 38).  

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Template concerning the notification of completion, discontinuation or interruption of the clinical 
trial for this is available on www.swissethics.ch. 
All biological materials and health-related data are archived and encrypted in a coded format upon 
termination of data analysis for 10 years.  
A final report is submitted to the Ethics Committee via BASEC within a year after completion or 
discontinuation of the study, unless a longer period is specified in the protocol (ClinO, Art. 38). 
6.6 Insurance 
In the event of study-related damage or injuries, the liability of the institution ETH Zürich provides 
compensation, except for claims that arise from misconduct or gross negligence.  
 
7 
FURTHER ASPECTS 
7.1 Overall ethical considerations 
The scientific value of this study lies in its evaluation of the bioavailability of leucine from a plant-
based protein drink as compared to an animal-based one. This research is particularly relevant 
in the field of nutrition science, as it addresses the challenge of developing sustainable, plant-
based protein sources that are nutritionally comparable to animal proteins. The study contributes 
significantly to the understanding of how plant-based diets can be optimized for enhanced human 
health, aligning with sustainability objectives in food production. 
 
Our team has formulated a plant-based drink that, based on preliminary data and specific 
formulations using a variety of plant sources, is expected to increase the bioavailability of leucine 
compared to drinks made from a single plant protein source. This aspect is crucial as it opens the 
possibility of creating plant-based protein options that are not only environmentally sustainable 
but also nutritionally effective. 
 
Currently, there is a gap in knowledge regarding how a beverage specifically optimized for amino 
acid bioavailability, particularly leucine, stacks up against traditional animal-based protein drinks. 
This study aims to fill that gap, providing valuable insights into the potential of plant-based proteins 
in meeting nutritional needs. 
 
Justification of Methodology: High-Performance Liquid Chromatography (HPLC) has been 
selected for its accuracy in measuring specific amino acids, such as leucine, in blood samples. 
This method is known for its precision, making it ideal for quantifying amino acid levels accurately. 
The use of a randomized crossover design in this study ensures that each participant serves as 
their own control. This approach significantly enhances the reliability of the results, as it reduces 
the variability that can arise from individual differences between participants. Standard 
procedures like fasting and routine blood sampling are incorporated to accurately assess the 
bioavailability of nutrients. Fasting ensures that the baseline levels of amino acids are consistent 
across participants, while routine blood sampling allows for the tracking of changes in leucine 
levels over time following the consumption of the test drinks. 
 
The balance of risk and benefits for the participants, and by extension, for society, is carefully 
considered in this study. Participation is voluntary, and participants are expected to visit the lab 
three times over a short period of three weeks, each visit lasting approximately 4 hours. They will 
be compensated CHF 100 for their time and expenses. The study involves minimal invasive 
procedures, including the consumption of an animal- or plant-based drink and blood sampling. 
Considering these aspects, the study is structured to maintain a fair balance between risks and 

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benefits, ensuring ethical integrity and participant safety while aiming to contribute valuable 
insights to the field of nutrition science. 
7.2 Risk-benefit assessment  
The assessments conducted in this research project are associated with minimal risk for the 
participants. Minor discomfort and risks associated with routine blood sampling. The volume of 
blood to be collected during each sampling is minimal, and the methodology adheres to 
established clinical standards to ensure participant safety. The primary risks associated with the 
procedure are limited to those commonly associated with routine venipuncture, such as temporary 
discomfort and bruising.  
 
The beverages utilized in this study encompass both commercially available drinks, composed of 
widely recognized ingredients, and a specially formulated non-commercial beverage composed 
of food-grade products. It is important to highlight that all ingredients used in both types of 
beverages are common and widely consumed, thus not introducing novel or unknown risks. 
Despite the normalcy of the ingredients, we acknowledge the unique formulation, as well as 
specific processing of the non-commercial beverage. We have taken utmost care to select 
ingredients with minimal allergenic potential, ensuring participant safety. Detailed information 
about the composition of both types of beverages will be provided during the informed consent 
process, and any participant concerns or questions related to allergens will be promptly 
addressed. 
 
The project acknowledges the risk of unauthorized data access and the unintended identification 
of project participants. To mitigate these risks, robust data security measures will be implemented. 
Access to sensitive information will be restricted to authorized personnel, and appropriate 
encryption techniques (unique identification code, section 8.3) will be applied to protect participant 
confidentiality. 
 
While the results of this research project may not yield immediate benefits for the participants, 
the study carries significant value in advancing our knowledge in plant-based nutrition. The 
research aims to contribute to the broader understanding of plant-based nutrition, potentially 
uncovering valuable insights that may benefit individuals and public health in the long term. The 
study holds the promise of contributing to the development of nutritionally equivalent plant-based 
alternatives to animal proteins. This has the potential to influence future dietary choices and 
support sustainable and health-conscious dietary practices. 
8 
QUALITY CONTROL AND DATA PROTECTION 
8.1 Quality measures  
Data handling and protection is conducted according to the data protection law in Switzerland. 
The Digital Trial Intervention Platform (dTIP https://dtip.ethz.ch/) will   monitor study conduction 
and data collection. Before the start of the study, the Principal Investigator will instruct and train 
the study personnel on how to correctly insert the data in the eCRF within the REDCap system, 
in close collaboration with dTIP.  During the study, data checks and queries will be regularly 
performed for each individual case to ensure data quality and integrity. All study personnel agree 
to allow the Principal Investigator and dTIP the direct access to all relevant study documents. At 
the end of data collection, the Principal Investigator and dTIP will perform a final check for data 
quality and integrity and blood samples that will be used for analysis will be inserted into an eCRF 
within the REDCap System. All queries will be resolved before data analysis. To ensure proper 
blood sampling, an experienced nurse will be responsible for collecting blood samples. 
Subsequent to the collection, trained study personnel will handle the preparation of blood samples 
and perform High-Performance Liquid Chromatography (HPLC) analyses. For quality assurance 
the sponsor, the Ethics Committee or an independent trial monitor may visit the research sites. 

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Direct access to the source data and all study related files is granted on such occasions. All 
involved parties keep the participant data strictly confidential.  
8.2 Data recording and source data 
This ensures accountability, regulatory compliance, and data integrity throughout the study, 
participants’ data will be collected and inserted by the project leader/study personnel into eCRF 
within the REDCap System. Project data resulting from the analyses of blood samples will be first 
inserted in an Excel file and stored in the ETH Server, and then transferred into an eCRF within 
the REDCap System. All data processing will be done locally and on password-secured 
computers of the ETH Zurich with a backup system. The REDcap System is implemented in the 
ETH server. 
 
Project-specific source data:  
• 
Patients’ characteristics and questionnaire inserted in an eCRF within the REDCap 
System; 
• 
Blood sample outcomes inserted in an Excel file stored in the ETH Server, and in an eCRF 
within the REDCap System. 
• 
Data collected in paper Case Report Forms (p-CRF) stored in a lockable cabinet in the 
Laboratory Exercise and Health, ETH Zürich  
 
REDCap maintains a built-in audit trail that logs all user activity and all pages viewed by every 
user, including contextual information (e.g. the project or record being accessed), entering data, 
exporting data, modifying a field, running a report, or add/modifying a use. 
8.3 Confidentiality and coding 
Trial and participant data will be handled with uttermost discretion and is only accessible to 
authorized personnel who require the data to fulfil their duties within the scope of the study. On 
the CRFs and other study specific documents, participants are only identified by a unique 
participant number. After recruitment, a study identification code will be generated for each 
participant. The study identification code is a unique alphanumerical code that prohibits the 
identification of the physical persons. All project-related data will be named using these 
identification codes. The code will be generated as a combination of letters and numbers based 
on (i) project name, (ii) participant number, (iii) year of birth (e.g., LEU011987). Health related 
personal data and biological samples of participants collected during the research project will all 
be named using these codes. Information about each participant identification code (e.g., name, 
address, date of birth) will be included in an Excel file, which is only accessible through name and 
password by the study personnel. The code will be broken if it is necessary to avert an immediate 
risk for the health of the concerned participant or to guarantee the rights of the participant (e.g., 
revoking the consent) or a legal basis exists for breaking the code. The coding will be done locally 
and on password-secured computers of the ETH Zurich with a backup system. 
 
Biological material in this study is not identified by participant name but by a unique participant 
number. Biological material is appropriately stored in a restricted area only accessible to the 
authorised personnel. Biological material is appropriately stored in a restricted area only 
accessible to authorized personnel. Specifically, blood samples will be stored at -80°C (freezer is 
water cooled, key lock protected and is hooked up to a central alarm) in the Laboratory of Exercise 
and Health in Schwerzenbach. The study primarily focuses on analyzing blood parameters, 
specifically screening for leucine levels, utilizing non-genetic data. 
8.4 Retention and destruction of study data and biological material 
All study data and biological material are archived for 10 years after study termination or 
premature termination of the study at the Laboratory of Exercise and Health, ETH Zürich. After 

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10 years all study data will be deleted and biological material will be destroyed upon autoclaving.  
9  MONITORING AND REGISTRATION 
dTIP will oversee the monitoring of the clinical study. This external oversight ensures 
compliance with the approved protocol, ethical standards, and regulatory requirements. dTIP 
will closely monitor study procedures, data collection, and promptly addressing any deviations 
or safety concerns. Source data/documents are accessible to monitors and questions are 
answered during monitoring. The study is registered Swiss National Clinical trial Portal (SNCTP) 
and the addition of the study in the Clingov.org registry is ongoing currently. 
10. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
The funding for the study is sourced from both ETH, Laboratory Exercise and Health and 
Innosuisse. The investigators will make every effort to present the research project results to 
national and international congresses, and - eventually - to publish the results of this pilot study 
in an international peer-reviewed journal. In terms of publication policy, the authors aim to adhere 
to recognized standards of academic integrity and transparency. They will ensure that appropriate 
authorship credit is given and that the raw data underlying the study findings are accessible to 
interested parties upon request. Timelines for publication may vary but will be pursued in a timely 
manner to facilitate the dissemination of results. Regarding data sharing policy, the investigators 
will uphold principles of data sharing where feasible and appropriate. They will consider requests 
for access to study data and collaborate with interested parties to facilitate meaningful analyses 
and interpretations. We will confirm that any observed gender effects will be disclosed in the final 
study report. The investigators declare no conflict of interest in planning, conducting and 
publishing the results of this study. 
11. REFERENCES 
1. 
Common Terminology Criteria for Adverse Events (CTCAE) 
https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf 
2. 
Declaration of Helsinki 
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-
medical-research-involving-human-subjects/ 
3. 
Federal Act on Data Protection (FADP) 
https://www.admin.ch/opc/en/classified-compilation/19920153/index.html 
4. 
Human Research Act (HRA) 
https://www.admin.ch/opc/de/classified-compilation/20061313/index.html 
5. 
International Conference on Harmonization (ICH) E6(R2) Guideline for Good Clinical 
Practice 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2
__Step_4_2016_1109.pdf 
6. 
International Conference on Harmonization (ICH) E2A Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC
500002749.pdf 
7. 
Ordinance on Clinical Trials in Human Research (ClinO) 
https://www.admin.ch/opc/de/classified-compilation/20121176/index.html 
 
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