Clinical trial NCT03667651: The PEBBLES Study - Testing a Strategy for Preventing Eczema and Food Allergy in High Risk Infants
Official title: THE PEBBLES STUDY: A Randomised Controlled Trial to Prevent Eczema, Food Allergy and Sensitisation Using a Skin Barrier Improvement Strategy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Eczema
Asthma
Allergy;Food
Lead sponsor: University of Melbourne
Sponsor class: OTHER
First posted: 2018-09-12
Enrollment: 760
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single blinded study design will be used
Primary purpose: PREVENTION

Brief summary: 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: 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..

Eligibility criteria: 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

Primary outcomes:
measure: Presence of eczema
timeFrame: 12 months of age.
measure: Confirmed diagnosis of food allergy at 12 months (52 weeks).
timeFrame: 12 months of age
Secondary outcomes:
measure: Eczema severity
timeFrame: 12 months of age
measure: Parent report of a community doctor diagnosis of eczema
timeFrame: 12 months of age
measure: infant skin barrier function
timeFrame: At 6 weeks and 12 months of age
measure: Parental compliance with a program to build infant skin barrier function
timeFrame: At 6 weeks and 6 months of age.
measure: Adverse events
timeFrame: From recruitment of infant until final study visit at 12 months of age.
measure: skin microbial colonisation, or skin lipid profile
timeFrame: At 6 weeks and 6 and 12 months of age
Other outcomes:
Locations:
city: Heidelberg
country: Australia
facility: Mercy Women's Hospital
state: Victoria
city: Parkville
country: Australia
facility: Frances Perry Private Hospital
state: Victoria
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Parkville
country: Australia
facility: Royal Women's Hospital
state: Victoria
Study officials:
affiliation: University of Melbourne
name: Adrian J Lowe, Doctorate
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lowe A, Su J, Tang M, Lodge CJ, Matheson M, Allen KJ, Varigos G, Sasi A, Cranswick N, Hamilton S, Robertson CF, Hui J, Abramson M, O'Brien S, Dharmage S. PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy. BMJ Open. 2019 Mar 13;9(3):e024594. doi: 10.1136/bmjopen-2018-024594.