Short-term Topical Application to Prevent Atopic Dermatitis

Study Overview
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Brief Summary
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This is a randomised, open-label, controlled study designed to investigate the effect of short-term neonatal skin barrier protection using a commercially available moisturiser on the prevention of atopic dermatitis and food allergy in high risk children.

Detailed Description
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Eczema, also known medically as Atopic Dermatitis (AD) is the most common skin disease of childhood, affecting 20% of Irish children, and is a general term for a group of skin conditions that cause the skin to become dry, red, itchy and inflamed. AD is often the first manifestation of atopic comorbidities including food allergy, asthma and allergic rhinitis. Recently published studies suggest that skin barrier preservation, with topically applied moisturisers in the first year of life, reduces the incidence of AD. Our own data suggests that an earlier window for this skin barrier protection may exist. This study is a randomised, open-label, controlled study and will investigate the effect of short-term neonatal skin barrier protection on the prevention of AD and food allergy in high risk infants. Infants with at least one parent with a positive history of atopic disease (AD, allergic rhinitis, asthma or food allergy) will be eligible for recruitment. The first study visit will take place within approximately 4 days of birth in the postnatal wards. At this visit, infants will be randomised to either treatment with skin barrier protection using a commercially available moisturiser or to standard routine skincare with no moisturiser from as soon as possible after birth until 2 months of age. This visit will also involve measurements of neonatal trans-epidermal water loss (TEWL) and natural moisturising factor (NMF) to assess skin barrier function and structure. Skin swabs will also be taken for microbiome and immune biomarker analysis. Follow-up assessments will take place at 2, 4 and 8 weeks, 6 and 12 months. Each visit will include a physical examination of the infant's skin, including TEWL and NMF measurements, and a questionnaire on infant health, bathing and skincare. Infant skin swabs will be taken again at 8 weeks and 12 months. A research nurse or doctor, blind to treatment allocation, will administer standardised assessments for the presence (yes/no), extent and severity of AD at 6 and 12 months. Suspected cases of food allergy will be investigated using skin prick testing (SPT) and oral food challenges. A DNA sample will be taken to test for filaggrin loss-of-function mutations, which are linked to AD risk. The primary outcome is AD at 12 months.

Official Title
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Short-term Topical Application to Prevent Atopic Dermatitis

Conditions
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Eczema Atopic Dermatitis, Eczema, Eczema, Infantile, Food Allergy

Intervention / Treatment
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* Other: Skin barrier protection in the first 2 months of life


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy full-term infants, gestational age >36+6 weeks. Infant has at least one parent with self-reported atopic dermatitis, food allergy, allergic rhinitis or asthma. Not requiring admission to the Neonatal Unit. Exclusion Criteria: No parental history of atopic disease. Admission to the Neonatal Unit for issues other than the establishment of normal feeding. Being administered oral or parenteral antibiotics. Receiving phototherapy for hyperbilirubinaemia. Sibling, including twin, already recruited. Other serious health issues (e.g. abdominal wall defects, congenital heart disease etc.) or a severe widespread skin condition (e.g. collodion). Any condition that would make the use of skin barrier protectant inadvisable or not possible (e.g. ankle talipes or developmental dysplasia of the hip, requiring a Pavlik's harness or casts). Participation in any other clinical trial of an investigational medicinal product.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 5 Days

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-centre, randomised, open-label, controlled study to evaluate whether short-term skin barrier protection using a moisturizer from birth to 2 months can prevent the onset of atopic dermatitis and food allergy at 12 months. Assessments of atopic dermatitis will be blinded.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional arm<br>Skin barrier protection in the first 2 months of life. | Other: Skin barrier protection in the first 2 months of life<br>* Skin barrier protection in the first 2 months of life using a commercially available moisturiser from birth 2 months. Twice daily, whole-body application.<br>|
| No Intervention: Control arm<br>Standard skincare advice. No moisturiser in the first 2 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of atopic dermatitis at 12 months. |  | 12 months | 
| Cumulative incidence of IgE-mediated food allergy at 2 years |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal changes in transepidermal water loss (TEWL) from birth to 12 months | TEWL measured at birth, 2, 4 and 8 weeks and at 6 and 12 months. | Birth to 12 months | 
| Longitudinal changes in natural moisturising factor (NMF) in the stratum corneum from birth to 12 months. | NMF measured by Raman spectroscopy at birth, 2, 4 and 8 weeks and at 6 and 12 months. | Birth to 12 months | 
| Microbial diversity and richness of the cheek and antecubital fossa (study subset). | Microbial community analysis (identification and abundance of a taxonomic units) will be used for the calculations of population diversity and richness indices (rarefaction, Shannon index, abundance-based coverage estimators (ACE), and Chao1) in a subset of study participants (n = 30 per study group). | Skin swabs for microbiome analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 
| Changes in skin microbial diversity and richness over the first year of life. | Comparison of microbial diversity and richness of the cheek and antecubital fossa between baseline, 8 weeks and 12 months (n = 30 per study group). | Skin swabs for microbiome analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 
| Comparison of microbial diversity and richness between the intervention and control groups. | Comparison of microbial diversity and richness of the cheek and antecubital fossa at each timepoint between the intervention (moisturiser) and control (no moisturiser) groups (n = 30 per study group). | Skin swabs for microbiome analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 
| Skin biomarker profile analysis of the cheek and antecubital fossa (study subset). | Cheek and antecubital fossa skin biomarker analysis, including interleukins, chemokines. and antimicrobial peptides (final list to be established) at birth, 8 weeks and 12 months (n = 30 from each study group). | Skin swabs for biomarker analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 
| Changes in skin biomarker profile between study over the first year of life. | Comparison of skin biomarker profiles of the cheek and antecubital fossa between baseline, 8 weeks and 12 months (n = 30 per study group). | Skin swabs for biomarker analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 
| Comparison of skin biomarker profiles between the intervention and control groups. | Comparison of skin biomarker profiles of the cheek and antecubital fossa at each timepoint between the intervention (moisturiser) and control (no moisturiser) groups (n = 30 per group). | Skin swabs for biomarker analysis will be taken at baseline (0-4 days), 8 weeks and 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eczema, Atopic dermatitis, Food allergy, Skin barrier, Filaggrin, Natural moisturizing factor, TEWL, Skin microbiome, Prevention, Moisturizer