Study of the Skin Microbiome and the Potential of a Topical Probiotic Cream for Atopic Dermatitis

Study Overview
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Brief Summary
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The skin microbiome of atopic dermatitis patients and healthy volunteers will be studies by collecting and analysing skin swabs on different timepoint. Additional, effort will be made to isolate and characterize Lactobacillus spp. and other beneficial micro-organisms on the skin. Second aim of this study is to evaluate a topical probiotic cream in atopic dermatitis treatment. A double-blind placebo-controlled intervention study will be performed in parallel with the skin microbiome analysis. Both clinical effect on the symptoms of atopic dermatitis and effect on the skin microbiome and survival of beneficial bacteria on the skin will be evaluated.

Detailed Description
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Probiotics are live micro-organisms which when administered in adequate amounts can exert a health benefit on the host. This health-promoting effects have been extensively studied in the gastrointestinal niche but it becomes more and more clear that other niches are also interesting for the potential of probiotics. Recent breakthroughs in 'next generation sequencing' (NGS) technologies are making it now possible to map the microbiota after DNA extraction, which is very interesting for bacteria that are not or difficult to cultivate. The research into the microbiota of the skin with such new NGS technologies shows that there is also an equilibrium in the skin composition of the microbiota and that there is a disturbance of the skin microbiota in atopic dermatitis (AD). The etiology of AD is complex, with the manifestation of the disease being influenced by various genetic and immune mechanisms acting in concert with environmental factors. A reduction in the skin microbial diversity is often observed and flares are characterized by an abundance of skin pathobionts such as Staphylococcus aureus. Therefore, topical probiotic strains could have a positive effect on the skin microbiome and function by inhibiting pathogens, restoring the skin microbiome and/or barrier function and executing anti-inflammatory effects on the skin cells. The main objectives of this study are to analyse the skin microbiome in healthy volunteers and patients AD to obtain in depth data of the composition of the skin microbiome and identify possible biomarkers for AD. In parallel, a double-blind placebo-controlled study with topically applied live lactobacilli will be performed to give more insights in the working mechanisms of lactobacilli on AD skin. More specifically to evaluate the effect of the 'live' Lactobacillus species as 'active ingredient' in relation to acne symptoms and skin microbiome modulation.

Official Title
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Study of the Skin Microbiome and the Potential of a Topical Probiotic Cream for Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Other: Topical cream with live probiotic bacteria
* Other: Placebo cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with atopic dermatitis and healthy volunteers Exclusion Criteria AD patients: no use of topical antibiotics and/or corticosteroids within 2 weeks before the start no use of oral antibiotics within 1 month before the start no immunodeficiency disease Exclusion Criteria Healthy Population: no use of topical antibiotics and/or corticosteroids within 2 weeks before the start no use of oral antibiotics within 1 month before the start no immunodeficiency disease no history of atopic dermatitis or other inflammatory skin disorders

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All AD patients will receive both treatments (verum and placebo). Verum cream will be applied on one side of the body (elbow or knee cavities), the placebo cream on the other side.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical cream with live probiotic bacteria (YUN)<br>Patients with atopic dermatitis using topical cream with live probiotic bacteria | Other: Topical cream with live probiotic bacteria<br>* Application of the probiotic cream once a day, for approximately 8 weeks on one side of the body (elbow or knee cavity; decided by doctor in advance, same as placebo cream). Assessment before product use (T0), after 4 and 8 weeks of product use (T4w and T8w, respectively) and after 4 weeks without product use (T12w).<br>* Other names: ACN cream (YUN);|
| Placebo Comparator: Placebo cream (YUN)<br>Patients with atopic dermatitis using placebo cream (same formulation as probiotic cream except live probiotic bacteria) | Other: Placebo cream<br>* Application of the placebo cream (same formulation as probiotic cream except live probiotic bacteria) once a day, for approximately 8 weeks on one side of the body (elbow or knee cavity; decided by doctor in advance, same as probiotic cream). Assessment before product use (T0), after 4 and 8 weeks of product use (T4w and T8w, respectively) and after 4 weeks without product use (T12w).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in skin microbiome composition | Extraction of microbial DNA out of skin swabs. Analysis of differences in bacterial communities colonizing the skin between healthy individuals and AD patients measured via Next Generation Sequencing techniques and qPCR assays. | AD patients: skin swabs at baseline,4 and 8 weeks of product use and 4 weeks without product use (total 12 weeks). Healthy volunteers: skin swab at baseline and after 12 weeks (no product use).. | 
| Change from baseline in AD severity scoring based on Eczema Area and Severity Index | Evaluation of atopic dermatitis symptoms via a scoring system based on Eczema Area and Severity Index (EASI). The EASI will be adjusted to the limited area of elbow or knee cavities. | AD patients: skin swabs at baseline,4 and 8 weeks of product use and 4 weeks without product use (total 12 weeks). Healthy volunteers: NA | 
| Change from baseline in itching via Visual Analogue Scale | The effect of the treatment of itching of the skin caused by atopic dermatitis lesions will be evaluated using Visual Analogue Scale (VAS). | AD patients: skin swabs at baseline,4 and 8 weeks of product use and 4 weeks without product use (total 12 weeks). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin microbiome, Probiotics, Lactobacillus spp.