A NOVel Moisturiser for Atopic Dermatitis: Effect on the Skin Barrier

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Randomised Controlled Trial of a NOVel Moisturiser for Atopic Dermatitis: Effect on the Skin Barrier in Adults With a Predisposition to a Skin Barrier Defect

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: 2% urea/20% glycerol cream
* Drug: Miniderm® 20% cream
* Drug: Diprobase® cream


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Every patient use three different creams (1 test cream, 2 reference creams) and one untreated area. They are their own controls
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test cream (2% urea/20% glycerol)<br>Topical cream, 1 Finger Tip Unit per treatment area on the lower volar forearms twice daily for 28 days | Drug: 2% urea/20% glycerol cream<br>* Moisturizing cream for topical application<br>* Other names: Canomini 20 mg/g + 200 mg/g cream;|
| Active Comparator: Reference cream 1: Miniderm® 20% cream (20% glycerol)<br>Topical cream, 1 Finger Tip Unit per treatment area on the lower volar forearms twice daily for 28 days | Drug: Miniderm® 20% cream<br>* Moisturizing cream for topical application<br>|
| Active Comparator: Reference cream 2: Diprobase® cream (cream without humectants)<br>Topical cream, 1 Finger Tip Unit per treatment area on the lower volar forearms twice daily for 28 days | Drug: Diprobase® cream<br>* Emollient cream for topical application<br>|
| No Intervention: Untreated<br>Untreated skin area on the volar forearm | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | day 29 prior to irritant application and day 31 following application | 
| 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 | 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 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 | Measured on day 29 and 31 | 
| 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. | Skin redness was scored on day 29 | 
| 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. | Skin redness was scored on day 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis, skin barrier, moisturiser, emollient