The PEBBLES Study - Testing a Strategy for Preventing Eczema and Food Allergy in High Risk Infants

Study Overview
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Brief Summary
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This is a phase III, single blind (outcome assessor is blinded), randomised controlled multicentre trial of the effect of EpiCeram emollient for improving and maintaining skin barrier function and reducing incidence of eczema and food allergy in high risk infants. A total of 760 participants with a first degree family history of allergic disease (asthma, eczema, allergic rhinitis or food allergy) will be recruited (380 each group) from maternity wards of three hospitals.

Detailed Description
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The primary objective of this study is to demonstrate that twice daily application of a ceramide dominant emollient reduces the risk of eczema and food allergy, when compared to standard skin management. Secondary objectives are to determine if twice daily application of a ceramide dominant emollient reduces the risk of infants developing allergic sensitisation (as measured by skin prick test); to determine if twice daily application of a ceramide dominant emollient improves infant skin barrier function; to determine the level of parental compliance with a program to build infant skin barrier function; to confirm that a ceramide dominant emollient does not cause adverse effects in infants; to determine the level of compliance required to demonstrate an improvement in infant skin barrier function and to determine if twice daily application of a ceramide dominant emollient influences infant skin microbial colonisation, or skin lipid profile. This is a phase III, single blind (outcome assessor is blinded), randomised controlled multicentre trial of the effect of EpiCeram emollient for improving and maintaining skin barrier function and reducing incidence of eczema and food allergy in high risk infants. A total of 760 participants with a first degree family history of allergic disease (asthma, eczema, allergic rhinitis or food allergy) will be recruited (380 each group) from maternity wards of three hospitals. Treatment will be from birth until six months, with a six week, six month and twelve month follow-up. An initial assessment will be performed at baseline which incorporates three surveys, a skin assessment, diary card (which is to be completed weekly and measures compliance), a breast milk sample, guthrie card and tape stripping. The six week and six month assessments entail a skin assessment, survey, compliance check, breast milk sample, tape stripping and guthrie card. Primary outcomes are assessed at the 12 month follow up where in addition to the aforementioned items, a saliva sample will also be taken and skin prick testing and food challenges will be performed when children have a positive SPT to one or more foods..

Official Title
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THE PEBBLES STUDY: A Randomised Controlled Trial to Prevent Eczema, Food Allergy and Sensitisation Using a Skin Barrier Improvement Strategy

Conditions
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Eczema, Asthma, Allergy;Food

Intervention / Treatment
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* Drug: EpiCeram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants will be eligible for this study if their mother, father, or an older sibling has a self-reported history of at least one of the following conditions: asthma, eczema/atopic dermatitis, hay fever/ allergic rhinitis or food allergy Exclusion Criteria: infants with any of the following will be excluded: A parent who has a known hypersensitivity to any of the ingredients of EpiCeram™ will be excluded, as it would be difficult for these parents to apply EpiCeram™ to their infant, and there is likely to be an increased risk of the infant reacting to the cream. Multiple births (twins, triplets etc.) will be excluded, due to the difficulty in randomising individual twins and because of the clustering effect of multiple children from the same family which would reduce the effective sample size of the study. Who are born premature (<36 weeks) as the effect of the intervention may be different in premature infants. Who have major birth or early life medical complications that require admission into a special care nursery, as it will be difficult for parents to comply with the study requirements. Whose parents do not have sufficient English language skills to be able to answer questions. Whose parents are not able to comply with all protocol required visits and procedures

Ages Eligible for Study
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Maximum Age: 3 Weeks

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: A single blinded study design will be used
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Twice daily use treatment with EpiCeram<br>They will be instructed to apply EpiCeram™ to the full skin surface of their child twice per day for 6 months. The prophylactic use of EpiCeram™ is the intervention that is being tested for its effect on infant skin barrier function. We will instruct parents to apply approximately 6 grams of EpiCeram™ per application at two regular times each day, including after bathing the infant, or at the time they would normally bathe their child. | Drug: EpiCeram<br>* Parents will be instructed to apply EpiCeram™ to the full skin surface of their child twice per day for six months.<br>|
| No Intervention: Standard skin care<br>Parents are to follow standard skin care practices | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of eczema | as assessed using i) the UK working party criteria for eczema and/or ii) blinded investigator observed eczema. | 12 months of age. | 
| Confirmed diagnosis of food allergy at 12 months (52 weeks). | This diagnosis is derived from a combination of allergic sensitisation, reaction history and food challenge. A skin prick test to six common allergens will be performed (egg white, cows' milk, peanut, dust mite, cat dander, and rye grass) along with a negative (saline) and a positive (histamine) control. Participants that are sensitised to certain foods (>=1mm wheal) during the skin prick testing will be given a challenge to determine if they are allergic to those foods. This will be conducted at the MCRI Allergy Clinic under the supervision of a Doctor specifically trained in oral food challenges. | 12 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eczema severity | assessed using the EASI score | 12 months of age | 
| Parent report of a community doctor diagnosis of eczema |  | 12 months of age | 
| infant skin barrier function | As assessed by Trans-epidermal water loss (Vapometer) | At 6 weeks and 12 months of age | 
| Parental compliance with a program to build infant skin barrier function | as assessed by parental completion of weekly diary cards and weighing of the tubes of study cream at each visit | At 6 weeks and 6 months of age. | 
| Adverse events | as assessed by the documentation of any untoward medical occurrence in a participant enrolled into this study | From recruitment of infant until final study visit at 12 months of age. | 
| skin microbial colonisation, or skin lipid profile | Assessed using skin swabs at baseline, 6 weeks and 12 months of age | At 6 weeks and 6 and 12 months of age |