An Exploratory Randomized Controlled Study to Evaluate the Effect of a Basic Skin Care Product on the Structural Strength of the Dermo-epidermal Junction
Phase: NA
Conditions: Healthy Skin
Sponsor: Prof. Dr. Jan Kottner

 
CHARITÉ –  UNIVERSITÄTSMEDIZIN BERLIN 
Gliedkörperschaft der Freien Universität Berlin und der Humboldt-Universität zu Berlin 
Charitéplatz 1  10117 Berlin  Telefon +49 30 450-50  www.charite.de 
KLINIK FÜR DERMATOLOGIE,  
VENEROLOGIE UND ALLERGOLOGIE 
Klinikdirektorin (komm.): Prof. Dr. med. U. Blume-Peytavi 
Charitéplatz 1 | 10117 Berlin 
Interne Geländeadresse: Rahel Hirsch Weg 2 
 
CLINICAL RESEARCH CENTER FOR HAIR AND SKIN SCIENCE 
Leiterin: Prof. Dr. med. U. Blume-Peytavi 
Stellv. Leiter: PD Dr. med. A. Vogt / PD Dr. rer cur. J. Kottner 
Tel:  +49 30 450 518 122 (Sekretariat Forschung)  
Tel.:  +49 30 450 518 178 (Studientelefon) 
Fax:  +49 30 450 518 952 / 998 
www.derma.charite.de / www.crcberlin.com 
Charité  Campus Mitte  10098 Berlin 
 
 
CONFIDENTIAL 
Study Protocol 
An exploratory randomized controlled study to evaluate the effect of a 
basic skin care product on the structural strength of the 
dermo-epidermal junction 
 
Code: CRC-SP-A-31 
 
Version 1.0, February 28, 2018 
 
 
INVESTIGATOR 
 
Dr. Jan Kottner 
Clinical Research Center for Hair and Skin Science, 
Department of Dermatology and Allergy,  
Charité – Universitätsmedizin Berlin 
Charitéplatz 1, 10117 Berlin, Germany 
Email: jan.kottner@charite.de 
 
 
 
 
PROTOCOL DEVELOPMENT 
PROTOCOL REVIEW 
Monira El Genedy 
Dr. Claudia Richter  
Dr. Jan Kottner 
Clinical Research Center for Hair and Skin Science, 
Department of Dermatology and Allergy,  
Charité – Universitätsmedizin Berlin 
Charitéplatz 1, 10117 Berlin, Germany 
Email: jan.kottner@charite.de 
Prof. Dr. phil. nat. Christian Surber,  
UniversitätsSpital Zürich 
Dermatologische Klinik 
Gloriastrasse 31 
CH-8091 Zürich, Schweiz 
M:  +41-79-366-5050 
Email: christian.surber@unibas.ch 
 
 
 
 
 

Study protocol 
Page 2 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
Table of contents 
 
1 Administrative Information ............................................................................................................ 3 
1.1 Title ........................................................................................................................................ 3 
1.2 Trial registration ..................................................................................................................... 3 
1.3 Protocol version ..................................................................................................................... 3 
1.4 Funding .................................................................................................................................. 3 
1.5 Roles and responsibilities ...................................................................................................... 3 
2 Introduction .................................................................................................................................. 4 
2.1 Background and Rationale ..................................................................................................... 4 
2.2 Objectives .............................................................................................................................. 5 
2.3 Trial design ............................................................................................................................ 5 
3 Methods: Participants, interventions, and outcomes ..................................................................... 6 
3.1 Study setting .......................................................................................................................... 6 
3.2 Eligibility criteria ..................................................................................................................... 6 
3.3 Interventions .......................................................................................................................... 7 
3.3.1 Concomitant Treatments ................................................................................................. 8 
3.4 Outcomes and variables ........................................................................................................ 9 
3.5 Participant timeline ............................................................................................................... 12 
3.6 Sample size ......................................................................................................................... 13 
3.7 Recruitment ......................................................................................................................... 13 
4 Methods: Assignment of interventions ........................................................................................ 14 
4.1 Allocation Sequence Generation .......................................................................................... 14 
4.2 Allocation implementation and concealment ........................................................................ 14 
4.3 Blinding ................................................................................................................................ 14 
5 Methods: Data collection, management, analysis ....................................................................... 15 
5.1 Data collection methods ....................................................................................................... 15 
5.2 Data management ............................................................................................................... 15 
5.3 Statistical methods ............................................................................................................... 15 
6 Methods: Monitoring ................................................................................................................... 16 
6.1 Data monitoring ................................................................................................................... 16 
6.2 Harms .................................................................................................................................. 16 
7 Ethics and dissemination ............................................................................................................ 17 
7.1 Research ethics approval ..................................................................................................... 17 
7.2 Protocol amendments .......................................................................................................... 17 
7.3 Informed Consent ................................................................................................................ 17 
7.4 Confidentiality ...................................................................................................................... 17 
7.5 Declaration of interests ........................................................................................................ 17 
7.6 Access to data ..................................................................................................................... 17 
7.7 Ancillary and post-trial care .................................................................................................. 18 
7.8 Dissemination policy ............................................................................................................ 18 
8 References ................................................................................................................................. 19 
9 Appendices ................................................................................................................................ 20 
 

Study protocol 
Page 3 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
1 Administrative Information 
 
1.1 Title 
An exploratory randomized controlled study to evaluate the effect of basic skin care products on 
the structural strength of the dermo-epidermal junction 
 
1.2 Trial registration 
Will be done at clinicaltrials.gov after positive approval by the Ethics Committee. 
 
1.3 Protocol version 
Version 1, February 28, 2018 
 
1.4 Funding 
This investigator-initiated study (IIS) is conducted and funded by the Clinical Research Center for 
Hair and Skin Science, Department of Dermatology and Allergy, Charité – Universitätsmedizin 
Berlin. 
 
1.5 Roles and responsibilities 
Project leader and Principal Investigator  
Priv.-Doz. Dr. Jan Kottner  
Clinical Research Center for Hair and Skin Science  
Department of Dermatology and Allergy  
Charité – Universitätsmedizin Berlin  
Charitéplatz 1, 10117 Berlin, Germany  
Phone: +49 30 450 518 218  
Fax: +49 30 450 518 998  
Email: jan.kottner@charite.de 
 
 
Protocol development 
Monira El Genedy 
Dr. Claudia Richter  
Dr. Jan Kottner 
Prof. Dr. Christian Surber 

Study protocol 
Page 4 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
2 Introduction 
 
2.1 Background and Rationale 
The world population is growing, and the life expectancy has risen continuously in developed and 
developing countries. One consequence is an increase of age associated disabilities and diseases 
(Kuhlmey A, 2008). The process of aging involves numerous structural and functional changes 
also affecting the skin. The skin is often considered as the largest organ of the human body and it 
fulfills a variety of protective and regulatory functions. Compared to other organs, the skin is 
constantly exposed to harmful environmental influences. Besides intrinsic factors these external 
factors may accelerate skin aging. Due to its ageing-related loss of functional capacity the skin 
becomes susceptible to develop adverse skin conditions and dermatological diseases (e.g. skin 
dryness, fungal infections) (Chang et al., 2013, Kottner et al., 2015). Especially old aged, care 
depended, and severely ill individuals are at high risk for developing severe skin injuries and 
wounds (e.g. decubitus, skin tears) with high social and economic impact. Empirical evidence 
indicates that the reduced adhesion of the dermal-epidermal junction is a major pathophysiological 
predictor for these types of injuries. 
 
In the field of skin research various non-invasive in vivo measurements are established, 
e.g. measurement of transepidermal water loss or stratum corneum hydration (du Plessis et al., 
2013). However, most of these measurements are indirect and these parameters only quantify the 
properties of the most superficial epidermal layers. The suction blister model is an artificial and 
controlled technique for dermal-epidermal separation along the dermo-epidermal junction (DEJ) 
(Unna, 1878, Kiistala and Mustakallio, 1964, Kiistala and Mustakallio, 1967). Empirical evidence 
suggests that the time of the dermal-epidermal separation (blistering time) is a measure of the 
dermo-epidermal adhesion. It has been proposed that the blistering time might be a clinically 
relevant parameter reflecting the mechanical integrity/stability of the dermo-epidermal junction 
(Hatje et al., 2015). 
 
Cosmetics and basic skin care products are widely used during the entire lifespan. People 
spent substantial amounts of money for that. In addition, topical skin care products are explicitly 
recommended to mitigate the increased risk in vulnerable populations, to protect the skin and to 
keep it intact. For instance, clinical practice guidelines recommend the use of topical skin care 
products to reduce the risk for pressure ulcer and skin tear development. However, the underlying 
working mechanisms of most basic skin care products are poorly understood. It is known that 
topically applied skin care products exhibit physical and chemical effects on and in the uppermost 
skin layers (e.g. the stratum corneum). Despite a few well known active ingredients (e.g. retinoids, 
vitamin C) exhibiting effects in the dermis, a particular skin protective effect of the vast majority of 
daily basic skin care applications on these deeper skin layers is unknown. Interestingly, results of a 
clinical trial including aged care residents from Australia suggest a protective effect of basic topical 

Study protocol 
Page 5 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
skin care application for preventing skin tears, but the underlying mechanism remains unclear 
(Carville et al., 2014). 
 
2.2 Objectives 
The main aim of this study is to investigate in a suction blister model, whether the use of a basic 
skin care formulation increases the mechanical integrity/adhesion of the dermo-epidermal junction.  
 
2.3 Trial design 
Exploratory randomized controlled study with a split body design on two investigational areas of 
the anterior side of both forearms.  
 

Study protocol 
Page 6 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
3 Methods: Participants, interventions, and outcomes 
 
3.1 Study setting 
The study will be conducted at the Clinical Research Center for Hair and Skin Science 
(CRC), Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin. 
Screening, inclusion and all study visits including the induction of the suction blisters and the 
measurement procedures will be conducted at the CRC. Daily application of the skin care 
product will be conducted at home by the subjects. 
 
3.2 Eligibility criteria 
Inclusion criteria 
 
 
Healthy volunteers and/or with stable chronic condition (e.g. controlled hypertension) 
 
Female, 
 
65 to 85 years, 
 
Caucasian, 
 
Phototype I to III according to the Fitzpatrick classification, 
 
Body Mass Index between 20 and 28 kg/m2, 
 
Non-smoker of at least one year, 
 
Absence of skin diseases or scars in the skin area of interest, 
 
Absence of tattoos in the skin area of interest, 
 
Able to give written informed consent, 
 
Willing and able to fulfill the study requirements 
 

Study protocol 
Page 7 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
Exclusion criteria 
 
 
Known or suspected defect of healing, 
 
Diabetes mellitus 
 
Any acute or chronic pathology that may interfere with the trial conduct, from 
investigator point of view, 
 
Acute or chronic wounds in the skin area of interest, 
 
Any skin affection which may interfere with the trial assessment, like urticaria,, 
psoriasis or scar on investigational areas, 
 
Medical history of skin cancer, 
 
History or establishment of diabetes or pre-diabetes, 
 
Any hyper-sensibility to one of the compounds of the investigational product, 
 
Any regular treatment which may affect the blood coagulation and hemostasis 
(anticoagulant medications, NSAID, etc.) before the suction blister induction (Visit 3 
and Visit 5), one NSAID to treat headache within four days is allowed 
 
Any physical treatment (like laser or surgery) on the arms within the last 6 months, 
 
Use of topical or systemic treatment on the investigational areas within the past 4 
weeks (topical hyaluronan, anti-inflammatory drugs, corticoids, retinoids, vitamin C, 
etc.) that would interfere with assessment and/or investigational treatments, 
 
Allergy to band-aid or to metals (such as nickel), 
 
UV sessions or strong sun exposure of the arms during the study period, 
 
Subject who cannot be contacted easily in case of necessity, 
 
Current participation in any other clinical study  
 
3.3 Interventions  
After giving informed consent and checking the in- and exclusion criteria, baseline skin 
measurements will be conducted (Table 3). After that one arm will be randomly selected. 
Subjects are instructed to apply on the selected forearm petrolatum (VASELINE, weiß 
Ph.Eur., Salbe). The other arm will remain untreated (control). The application of the skin 
care product will be twice a day in the morning and in the evening for 4, respectively 8 
weeks. This should be done after washing or showering to allow the product to stay on the 
skin during day/ night. 
 
 
 

Study protocol 
Page 8 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
Subject instructions  
The subjects should inform the Investigator before using any systemic treatment which may 
interfere with the study assessments. Some treatments are prohibited throughout the study.  
 
During the study, the subjects will be instructed not to:  
 
have sun exposure or UV-light sessions on the investigational areas,  
 
Use any topical drug or cosmetic product on the investigational areas on both arms 
(except usual cleaning products) which may interfere with the trial assessment 
(topical hyaluronan, anti-inflammatory drugs, corticoids, retinoids, α-hydroxy acids, 
vitamin C).  
 
have physical treatments on the investigational areas.  
 
3.3.1 Concomitant Treatments 
 
Prohibited concomitant treatments 
 
Any topical drug (hyaluronan, anti-inflammatory drugs, corticoids, retinoids, vitamin C, 
corticoids, etc.) on investigational areas until the last assessment  
 
Any systemic treatment which may interfere with either investigational products or 
study conduct (anti-inflammatory drugs, corticoids, retinoids, vitamin C, corticoids, 
etc.) for more than 5 consecutive days until the last assessment 
 
Any treatment which may affect the blood coagulation and hemostasis (anticoagulant 
medications, NSAID, etc.) 
 
Allowed concomitant treatments 
The associated treatments which are considered necessary and not interfering with either 
investigational products or study conduct can be used on decision of the Investigator. The 
drug names (INN), their indication, dose and duration will be recorded in the CRF in 
concomitant treatments section. 

Study protocol 
Page 9 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
3.4 Outcomes and variables 
Because this is an exploratory study, no distinction is be made between primary and 
secondary outcomes. 
 
Name 
Method and metric 
Time points of data 
collection 
Blistering Time  
- Visual inspection 
- Duration from start of suction 
pressure to appearance of first 
vesicles in minutes 
- Duration from start of suction 
pressure to development of full 
blister in minutes (Appendix 4) 
 
Visit 3, Visit 5 
Skin surface Temperature 
- Measurement with Skin-
Thermometer ST 500 
(Courage+Khazaka electronic 
GmbH)  
- Means of duplicate 
measurements per skin area in 
°C per skin area  
 
Visit 3, Visit 5 
Stratum corneum hydratation 
(SCH) 
- Corneometer CM 825 
(Courage + Khazaka, Cologne, 
Germany) (Appendix 5) 
- Means of duplicate 
measurements per skin area in 
arbitrary units  
 
Visit 1, Visit 2, Visit 3, 
Visit 4, Visit 5, Visit 6 
Epidermal and dermal 
hydratation 
- Measurement with 
MoistureMeterEpiD (Delfin 
Technologies) (Appendix 6) 
- Percentage of tissue water (0-
100%) (0,5mm measurement 
depth)  
 
Visit 1, Visit 2, Visit 3, 
Visit 4, Visit 5, Visit 6 
Epidermal thickness  
 
- OCT (Thorlabs, Lübeck, 
Germany), measurements 
according to Trojahn et al. 2015  
 μm) (Appendix 8) 
 
Visit 1, Visit 3, Visit 5, 
Visit 6 
 
 
 

Study protocol 
Page 10 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
Name 
Method and metric 
Time points of data 
collection 
Age 
Checking by looking at the 
ID card (metric)  
Screening 
Body temperature 
Clinical thermometer in °C  
Screening 
Heart rate 
Beats per minute (bpm)  
Screening 
Blood pressure 
Millimeters of mercury 
(mmHg) 
Screening 
BMI (body height and 
weight) 
kg/m2  
 
Screening 
Phototype 
Categories I, II, III  
Screening 
 
 
 
Both arms will be subdivided in two investigational areas, called “Area A” (upper part of the 
middle of the right volar forearm) respectively “Area C” (upper part of the middle of the left 
volar forearm) and “Area B” (lower part of the middle of the right volar forearm) respectively 
“Area D” (lower part of the middle of the left volar forearm) (Figure 1).  
After 4 weeks (Visit 3) 2 suction blisters (Appendix 4) will be raised at the investigational 
Areas A or B at the right volar forearm (Figure 2). Another 2 suction blisters will be raised at 
the left volar forearm at the investigational Areas C or D (Figure 2). The allocation of the 
respective area for suction blister induction is decided via a randomization list.  
After 4 additional weeks (Visit 5), 2 more suction blisters will be raised in each of the 
remaining so far non-blistered investigational Areas.  
 
After the blister has been raised, the blister fluid will be punctured and a dressing 
applied to allow the wound to heal. The skin areas where suction blisters have been raised 
after 4 weeks will not be treated during the following 8 weeks. 
 
Before any measurements or induction of the suction blisters, the study volunteers will be 
requested to acclimatize for 30 minutes at 40 to 60 % relative humidity and a temperature of 
20 to 22 °C with having both forearms uncovered.  
 
Sequence of measurements (Visit 1, 2, 3, 4, 5 and 6) 
(1) Skin surface temperature  
(2) Stratum corneum hydration (SCH)  
(3) Epidermal and dermal hydration  
(4) Skin thickness  

Study protocol 
Page 11 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
Measurements will be performed two times per measurement area. Every value will be 
recorded separately. 
 
Figure 1. Localization of investigational skin areas 
 
 
 
 
 
 
 
 
Figure 2. Localization of suction blisters 
 

Study protocol 
Page 12 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
3.5 Participant timeline 
Table 1. Participant timeline 
 
Visit 0 
Screening 
Visit 1  
Inclusion 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
 
D-14 to D0 
D0 
D14±1 
D28±2 
D42±2 
D56±2 
D66±3 
Informed consent  
X 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Vital signs 
X 
 
 
 
 
 
 
Physical examination 
X 
 
 
 
 
 
 
In-/exclusion criteria 
X 
X 
 
 
 
 
 
BMI 
X 
 
 
 
 
 
 
Randomization of arms 
 
X 
 
 
 
 
 
Instruction how to treat the treatment arm  
 
X 
X 
X 
X 
 
 
Handout of products 
 
X 
 
X 
 
 
 
Treatment 
 
 
 
 
 
 
 
Record concomitant medication, therapies, procedures 
X 
X 
X 
X 
X 
X 
X 
Investigational sites identification 
 
X 
 
 
 
 
 
Blister Induction* 
 
 
 
X 
 
X 
 
Check for blister healing 
 
 
 
 
X 
 
X 
Stratum corneum hydratation  
 
X 
X 
X 
X 
X 
 
Epidermal and dermal hydratation 
 
X 
X 
X 
X 
X 
 
Epidermal thickness  
 
X 
 
X 
 
X 
 
Record AEs 
 
X 
X 
X 
X 
X 
X 
Return investigational products 
 
 
 
 
 
X 
 
*Randomization 

Study protocol 
Page 13 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
3.6 Sample size  
Due to the explorative character of this study, a formal sample size estimation is not 
performed. It is planned to include 12 healthy female subjects. 
 
Subject replacement 
In this study, a subject withdrawn from the study for any reason will be replaced.  
 
3.7 Recruitment 
Subjects will recruited via advertisements and/or contacted directly. 
 

Study protocol 
Page 14 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
4 Methods: Assignment of interventions 
 
There will be a concealed random allocation of the treatment arm (left vs. right) and area of 
suction blister induction (“Area A”/ “Area C” vs. “Area B”/ “Area D”). 
 
4.1 Allocation Sequence Generation 
Two independent simple randomization lists (left vs. right arm and “Area A”/ “Area C” vs. 
“Area B”/ “Area D”) will be created by the data manager not involved in the study. The data 
manager will also prepare sequentially numbered opaque sealed envelopes containing the 
allocation. 
 
4.2 Allocation implementation and concealment 
The numbered opaque sealed envelopes are stored at the CRC. Envelopes containing the 
assignment to the treatment arm will be opened after confirming eligibility provision of 
informed consent at Day 0. Envelopes containing the assignment of suction blister area  will 
be opened at visit 3. 
 
4.3 Blinding 
Due to the nature of the intervention, neither the investigators nor the participants will be 
blinded.

Study protocol 
Page 15 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
5 Methods: Data collection, management, analysis  
 
5.1 Data collection methods 
All data collectors will be trained in obtaining accurately the variables of interest. Paper 
source data (SD) will be used to document all study variables of interest (data collection 
forms see appendix 3).  
 
Medical examination 
The medical examination performed before inclusion will include a subject’s interview on her 
medical history and a clinical examination, to make sure of the subject’s eligibility.  
 
Suction blister creation 
The Suction blister model is an artificial and controlled technique for dermal-epidermal 
separation. Over the course of this study a total of 8 suction blisters with 8 mm in diameter 
are produced at the middle of the volar forearms of one volunteer. The comparisons of the 
blistering times (in minutes) will be used as outcome to detect possible treatment effects. 
Two suction blisters will be induced on each investigational area for two independent 
measurements of the blistering time. The technical procedure of suction blister wound 
creation is presented in the SOP Appendix 4. 
 
5.2 Data management 
The data manager creates an SPSS file and data of the SD are entered (single data entry). 
After data are entered, a random subset will be verified by an independent person (SD 
verification) who was not involved in the data entry so far. 
 
5.3 Statistical methods 
Demographic and other characteristics will be described using mean and spread parameters 
or proportions. The skin measurement results including the time(s) to blistering will be 
described using medians and interquartile ranges per skin area and time and displayed in 
grouped bar graphs. No statistical tests will be applied.

Study protocol 
Page 16 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
6 Methods: Monitoring 
6.1 Data monitoring 
Data monitoring is not planned. 
 
6.2 Harms 
Within this trial, the following definitions of adverse events will be used: 
 
Adverse Event (AE) 
Adverse events are defined in this study as any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs in patients, related to the intervention. Adverse 
events reported to the investigator must be recorded on the adverse event page of the data 
collection form and should be described. 
 
Serious Adverse Event (SAE)  
Adverse Event that:  
i. leads to death;  
ii. leads to a serious deterioration in the health of the subject, that either resulted in;  
a life-threatening illness or injury, or  
a permanent impairment of a body structure or a body function; or  
prolonged hospitalization; or,  
medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function; or  
iii. led to foetal distress, foetal death or a congenital abnormality or birth defect.  
 
Note: Planned hospitalization for a pre-existing condition, without serious deterioration in 
health, is not considered a serious adverse event. 
 

Study protocol 
Page 17 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
7 Ethics and dissemination 
7.1 Research ethics approval 
An approval to conduct the study will be obtained from the local ethics committee of the 
Charité-Universitätsmedizin Berlin. 
 
7.2 Protocol amendments 
The ethics committee will be informed about possible study amendments. 
 
7.3 Informed Consent 
Subjects meeting the inclusion criteria must provide written informed consent prior to 
participation. The informed consent form (ICF) must be dated and signed by the study 
participant herself. The originally signed consent form is archived in the investigator site file. 
Study participants receive copies of the written information sheet, and the signed informed 
consent form.  
The patient information sheet, informed consent form and all other documents handed out to 
the study participant will be submitted for approval to the ethics committee before use.  
Any study participants can withdraw her consent at any time without giving reasons. 
 
7.4 Confidentiality 
All personal data are collected under pseudonymization. Each patient gets a distinct subject 
number. The investigator administrates the subject identification list, which includes the 
subject number as well as name, birthday and address of the subject. The access to this is 
limited, only the investigators as well as the authorized study staff, will have permission to 
inspect this list. All study-related information will be stored securely at the CRC. All 
participant information will be stored in locked file cabinets in areas with limited access. 
Digital data are stored on a secured digital server of the Charité-Universitätsmedizin Berlin. 
 
7.5 Declaration of interests 
 
None declared.  
 
7.6 Access to data 
Because this is an IIS, the data is owned by the responsible researcher and therefore has full 
access. 

Study protocol 
Page 18 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
7.7 Ancillary and post-trial care 
Not planned. 
 
7.8 Dissemination policy 
A clinical study report will be prepared. Results will be also made available at the trial register 
clinicaltrial.gov. The study results will be presented in an international scientific journal 
following the guidance of the CONSORT 2010 statement (Schulz et al., 2010). Any 
publication will take account of the ‘Uniform requirements for manuscripts submitted to 
biomedical journals’. 
 

Study protocol 
Page 19 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
8 References  
Carville, K., Leslie, G., Osseiran-Moisson, R., Newall, N. and Lewin, G. (2014) The 
effectiveness of a twice-daily skin-moisturising regimen for reducing the incidence of 
skin tears. Int Wound J, 11, 446-453. 
Chang, A.L., Wong, J.W., Endo, J.O. and Norman, R.A. (2013) Geriatric dermatology 
review: Major changes in skin function in older patients and their contribution to 
common clinical challenges. J Am Med Dir Assoc, 14, 724-730. 
du Plessis, J., Stefaniak, A., Eloff, F., John, S., Agner, T., Chou, T.C., Nixon, R., Steiner, 
M., Franken, A., Kudla, I. and Holness, L. (2013) International guidelines for the in 
vivo assessment of skin properties in non-clinical settings: Part 2. transepidermal 
water loss and skin hydration. Skin Res Technol, 19, 265-278. 
Hatje, L.K., Richter, C., Blume-Peytavi, U. and Kottner, J. (2015) Blistering time as a 
parameter for the strength of dermoepidermal adhesion: a systematic review and 
meta-analysis. Br J Dermatol, 172, 323-330. 
Kiistala, U. and Mustakallio, K.K. (1964) In-Vivo Separation of Epidermis by Production of 
Suction Blisters. Lancet, 2, 1444-1445. 
Kiistala, U. and Mustakallio, K.K. (1967) Dermo-epidermal separation with suction. 
Electron microscopic and histochemical study of initial events of blistering on human 
skin. J Invest Dermatol, 48, 466-477. 
Kottner, J., Lichterfeld, A., Blume-Peytavi, U. and Kuhlmey, A. (2015) [Skin health 
promotion in the elderly]. Z Gerontol Geriatr, 48, 231-236. 
Kuhlmey A, S.D. (2008) Alter, Gesundheit und Krankheit.  Bern: Hans Huber. 
Schulz, K.F., Altman, D.G. and Moher, D. (2010) CONSORT 2010 statement: Updated 
guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother, 
1, 100-107. 
Trojahn, C., Dobos, G., Richter, C., Blume-Peytavi, U. and Kottner, J. (2015) Measuring 
skin aging using optical coherence tomography in vivo: a validation study. J Biomed 
Opt, 20, 045003. 
Unna, P. (1878) Zur Anatomie der Blasenbildung an der menschlichen  Haut. Vjschr 
Dermatol Syphil, 5, 3. 
 
 

Study protocol 
Page 20 of 20 
 
Study code CRC-SP-A-31 
Version 1.0, February 28, 2018 
 
9 Appendices 
Appendix 1: Subject information leaflet (in German)  
Appendix 2: Informed consent form (in German)  
Appendix 3: Data collection forms 
Appendix 4: Suction blister creation and time measurement 
Appendix 5: Technical Procedure Corneometer 
Appendix 6: Technical Procedure MoistureMeterEpid 
Appendix 7: Procedure OCT 
Appendix 8: Technical Procedure OCT-Bestimmung der epidermalen Hautdicke