Dermatitis, Atopic
Conditions
Keywords
atopic dermatitis, skin barrier, moisturiser, emollient
Brief summary
Atopic dermatitis (AD) is among the most common chronic types of inflammatory skin disease and it is characterised by exacerbations or relapses over years. The patients have a genetically impaired skin barrier that can be evaluated by measuring the transepidermal water loss (TEWL), which is increased in both dry skin and clinically normal skin in AD patients. Moisturisers are first line treatment for AD patients and moisturisers are the most prescribed products in dermatology. The use of moisturisers have been found to reduce the need for steroids. The newly developed moisturizing cream 1107.57 is intended for people with dry skin symptoms, such as dryness, itching, and flaking. As most people with dry skin of different origin have an impaired skin barrier function, it is important to investigate the possible influence on the skin barrier after long-term (several weeks') treatment. It is of utmost importance to evaluate different moisturisers head-to-head in order to facilitate an evidence-based choice of moisturiser. The primary objective of the trial is to determine whether applying the test cream 1107.57 for 4 weeks is superior in terms of skin barrier strengthening, when compared with (1) no treatment and (2) two reference creams in adults with a predisposition to a skin barrier defect. Secondary objectives are to determine whether there is a difference between 1107.57 and (1) no treatment and (2) the two reference creams in skin moisturization, tolerability, cream consumption and safety. Participants will treat their lower volar forearms for 28 days with three different creams (test cream and two reference creams) and leave one area untreated as a control. Each forearm will have two different treatment areas and treatment allocation will be randomized. One Finger Tip Unit (FTU) of each cream will be applied twice daily on the designated study area for 28 days. On day 1 and 29 the transepidermal water loss (TEWL) and skin capacitance is measured on their forearms to evaluate the effect on skin barrier function and skin hydration. Furthermore, on day 31, after challenge with 1 % sodium lauryl sulphate (SLS) on day 29, the susceptibility to irritation caused by SLS will be evaluated visually and by measuring TEWL on their forearms. Study participants will attend visits at the start of randomised therapy and on day 5, 15, 29 and 31. During the study period the participants will also grade and evaluate the tolerability of the different creams.
Interventions
DRUG2% urea/20% glycerol cream
Moisturizing cream for topical application
DRUGMiniderm® 20% cream
Moisturizing cream for topical application
DRUGDiprobase® cream
Emollient cream for topical application
Sponsors
University of Sheffield
ACO Hud Nordic AB
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Every patient use three different creams (1 test cream, 2 reference creams) and one untreated area. They are their own controls
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The participants have to meet all of the following criteria to be eligible to enter the study: * Willing and able to provide informed consent * Male or female and aged 18 years or above * Volunteers able to read and understand English * A personal history of atopic dermatitis
Exclusion criteria
Participants meeting any of the following criteria will not be permitted to enter the study: * Eczema on the volar forearms requiring anti-inflammatory treatment * Possible allergy to ingredients in the study medications. * Any serious current medical condition which, in the opinion of the Investigator, may interfere with the evaluation of the results or may be contraindicated by the use of the test medications * Use of any concomitant medication that may interfere with the study related activities or assessment of efficacy, as judged by the Investigator * Use of any topical product, including cosmetic leave-on products on the volar forearms, within 1 week prior to, and throughout the study * Female participant who, according to the participant, is pregnant or breast-feeding, or plans to become pregnant during the course of the study * Any participant-related factor suggesting potential poor compliance with study procedures (e.g. psychiatric disorders, history of alcohol or substance abuse), as judged by the Investigator * Enrolment in any interventional study or use of an investigational drug within 3 months prior to the screening visit * Volunteers judged by the PI to be inappropriate for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation | day 29 prior to irritant application and day 31 following application | The change in TEWL from treated and untreated skin before and after induction of skin irritation with SLS. SLS increases TEWL. An effective treatment protects skin from irritation and less TEWL increase is anticipated compared to untreated skin |
| Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31) | The 2D Skin Imaging was performed on day 15, day 29 and on day 31. Only day 29 and 31 was included in the statistical analysis | Skin redness measurement by Objective Erythema (2D Skin Imaging) on treated and untreated skin before (day 29) and after (day 31) induction of skin irritation with SLS. Captured 2D images are analysed to determine the skin erythema index (degree of redness, arbitrary numerical value), where a higher value denotes a stronger reaction/more redness. An effective treatment is anticipated to protect the skin from irritation, i.e. a weaker reaction from SLS/less redness compared to the untreated skin. Data is presented as change from day 29 to day 31 |
| Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31) | Measured on day 29 and 31 | Objective skin redness measurement by Mexameter on treated and untreated skin before (day 29) and after (day 31) induction of skin irritation with SLS. Skin redness is measured using a C&K Mexameter probe to quantify SLS-induced skin irritation (arbitrary numerical scale). An effective treatment is anticipated to protect the skin from irritation, i.e. a weaker reaction from SLS/less redness compared to the untreated skin. Data is presented as change from day 29 to day 31 |
| Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring | Skin redness was scored on day 29 | Skin redness by visual scoring on treated and untreated skin before induction of skin irritation with SLS. Skin redness was evaluated on a 4-point visual scale from 0 to 3, where 0 indicates no redness/reaction and 3 indicates strong erythema. |
| Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring | Skin redness was scored on day 31 | Skin redness by visual scoring on treated and untreated skin after induction of skin irritation with SLS. Skin redness was evaluated on a 4-point visual scale from 0 to 3, where 0 indicates no redness/reaction and 3 indicates strong erythema. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Medications prohibited to use \>28 Days, 28 Days, 14 Days and 7 Days, respectively, Prior to Baseline/Day 1 and throughout the study are listed in the Clinical Trial Protocol Use of bland (non-medicated) emollients, moisturisers or sunscreen on the test areas, within 7 days prior to Visit 1 was also prohibited Use of bland (non-medicated) emollient(s) was permitted during the study to manage dry skin in areas surrounding but not on or overlapping the test areas.
Participants by arm
| Arm | Count |
|---|---|
| Subject Using 3 Creams Each subject used three creams on their volar forearms and had one skin area untreated 4 treated skin areas: Test cream Glycerol cream Cream without humectants Untreated | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Subject Using 3 Creams |
|---|---|
| Age, Continuous | 37.6 years STANDARD_DEVIATION 16.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United Kingdom | 49 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 49 | 0 / 49 | 0 / 49 |
| other Total, other adverse events | 1 / 49 | 6 / 49 | 15 / 49 | 0 / 49 |
| serious Total, serious adverse events | 0 / 49 | 0 / 49 | 0 / 49 | 0 / 49 |
Outcome results
Primary
Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring
Skin redness by visual scoring on treated and untreated skin after induction of skin irritation with SLS. Skin redness was evaluated on a 4-point visual scale from 0 to 3, where 0 indicates no redness/reaction and 3 indicates strong erythema.
Time frame: Skin redness was scored on day 31
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Cream (2% Urea/20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring | 0.99 units on a scale | Standard Deviation 0.691 |
| Reference Cream 1: Miniderm® 20% Cream (20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring | 1.08 units on a scale | Standard Deviation 0.649 |
| Reference Cream 2: Diprobase® Cream (Cream Without Humectants) | Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring | 1.45 units on a scale | Standard Deviation 0.718 |
| Untreated | Skin Barrier Strengthening Effect by Measurement of Skin Redness After Induction of Skin Irritation as Assessed by Visual Scoring | 1.35 units on a scale | Standard Deviation 0.68 |
Comparison: Summary of Visual Redness at day 31p-value: <0.00195% CI: [-0.558, -0.15]ANCOVA
Comparison: Summary of Visual Redness at day 31p-value: 0.39295% CI: [-0.292, 0.115]ANCOVA
Comparison: Summary of Visual Redness at day 31p-value: <0.00195% CI: [-0.652, -0.242]ANCOVA
Primary
Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31)
Objective skin redness measurement by Mexameter on treated and untreated skin before (day 29) and after (day 31) induction of skin irritation with SLS. Skin redness is measured using a C&K Mexameter probe to quantify SLS-induced skin irritation (arbitrary numerical scale). An effective treatment is anticipated to protect the skin from irritation, i.e. a weaker reaction from SLS/less redness compared to the untreated skin. Data is presented as change from day 29 to day 31
Time frame: Measured on day 29 and 31
Population: In some participants it was not possible to analyze all images, therefore the Overall Number of Participants Analyzed in this outcome measure differs compared to the total number of participants included in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Cream (2% Urea/20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31) | 80.859 Arbitrary Units | Standard Deviation 53.901 |
| Reference Cream 1: Miniderm® 20% Cream (20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31) | 82.893 Arbitrary Units | Standard Deviation 53.15 |
| Reference Cream 2: Diprobase® Cream (Cream Without Humectants) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31) | 106.39 Arbitrary Units | Standard Deviation 56.315 |
| Untreated | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by Mexameter (Change From Day 29 to Day 31) | 98.951 Arbitrary Units | Standard Deviation 53.917 |
Comparison: Summary of Redness-Mexameter change from day 29 to day 31p-value: 0.00295% CI: [-31.325, -6.829]ANCOVA
p-value: 0.47195% CI: [-16.787, 7.801]ANCOVA
Comparison: Summary of Redness - Mexameter change from day 29 to day 31p-value: <0.00195% CI: [-39.372, -14.698]ANCOVA
Primary
Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31)
Skin redness measurement by Objective Erythema (2D Skin Imaging) on treated and untreated skin before (day 29) and after (day 31) induction of skin irritation with SLS. Captured 2D images are analysed to determine the skin erythema index (degree of redness, arbitrary numerical value), where a higher value denotes a stronger reaction/more redness. An effective treatment is anticipated to protect the skin from irritation, i.e. a weaker reaction from SLS/less redness compared to the untreated skin. Data is presented as change from day 29 to day 31
Time frame: The 2D Skin Imaging was performed on day 15, day 29 and on day 31. Only day 29 and 31 was included in the statistical analysis
Population: In some participants it was not possible to analyze all images, therefore the Overall Number of Participants Analyzed in this outcome measure differs compared to the total number of participants included in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Cream (2% Urea/20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31) | 13.261 Arbitrary Units | Standard Deviation 6.9086 |
| Reference Cream 1: Miniderm® 20% Cream (20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31) | 14.833 Arbitrary Units | Standard Deviation 6.044 |
| Reference Cream 2: Diprobase® Cream (Cream Without Humectants) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31) | 17.981 Arbitrary Units | Standard Deviation 7.355 |
| Untreated | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before and After Induction of Skin Irritation as Assessed by the Erythema Index (Change From Day 29 to Day 31) | 16.747 Arbitrary Units | Standard Deviation 6.7629 |
Comparison: Summary of Objective Erythema (2D Skin Imaging) change from day 29 to day 31p-value: <0.00195% CI: [-5.114, -1.962]ANCOVA
Comparison: Summary of Objective Erythema (2D Skin Imaging) change from day 29 to day 31p-value: 0.03195% CI: [-3.332, -0.164]ANCOVA
Comparison: Summary of Objective Erythema (2D Skin Imaging) change from day 29 to day 31p-value: <0.00195% CI: [-6.332, -3.156]ANCOVA
Primary
Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring
Skin redness by visual scoring on treated and untreated skin before induction of skin irritation with SLS. Skin redness was evaluated on a 4-point visual scale from 0 to 3, where 0 indicates no redness/reaction and 3 indicates strong erythema.
Time frame: Skin redness was scored on day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Cream (2% Urea/20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring | 0 units on a scale | Standard Deviation 0 |
| Reference Cream 1: Miniderm® 20% Cream (20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring | 0 units on a scale | Standard Deviation 0 |
| Reference Cream 2: Diprobase® Cream (Cream Without Humectants) | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring | 0 units on a scale | Standard Deviation 0 |
| Untreated | Skin Barrier Strengthening Effect by Measurement of Skin Redness Before Induction of Skin Irritation as Assessed by Visual Scoring | 0 units on a scale | Standard Deviation 0 |
Primary
Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation
The change in TEWL from treated and untreated skin before and after induction of skin irritation with SLS. SLS increases TEWL. An effective treatment protects skin from irritation and less TEWL increase is anticipated compared to untreated skin
Time frame: day 29 prior to irritant application and day 31 following application
Population: Each participant used three creams on their volar forearms and one skin area was left untreated. A skin irritant was applied on each treatment area (n=4) after end of cream treatment period. The irritant was left on the skin for 24h and the Trans Epidermal Water Loss (TEWL) was measured after another 24h and compared to TEWL measured after treatment but before application of irritant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Cream (2% Urea/20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation | 19.790 TEWL (g/m^2·h) change from day 29 to 31 | Standard Deviation 13.86 |
| Reference Cream 1: Miniderm® 20% Cream (20% Glycerol) | Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation | 24.680 TEWL (g/m^2·h) change from day 29 to 31 | Standard Deviation 14.693 |
| Reference Cream 2: Diprobase® Cream (Cream Without Humectants) | Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation | 29.648 TEWL (g/m^2·h) change from day 29 to 31 | Standard Deviation 14.299 |
| Untreated | Skin Barrier Strengthening Effect by Measurement of Trans Epidermal Water Loss (TEWL) Before and After Induction of Skin Irritation | 28.646 TEWL (g/m^2·h) change from day 29 to 31 | Standard Deviation 13.668 |
Comparison: Summary of TEWL (g/m2h) change from day 29 to day 31p-value: <0.00195% CI: [-12.562, -5.489]ANCOVA
Comparison: Summary of TEWL (g/m2h) change from day 29 to day 31p-value: 0.02195% CI: [-7.76, -0.629]ANCOVA
Comparison: Summary of TEWL (g/m2h) change from day 29 to day 31p-value: <0.00195% CI: [-12.602, -5.44]ANCOVA