Clinical trial NCT03270566: Softened Water for Eczema Prevention Pilot Trial
Official title: An Outcome Assessor-blinded Pilot Randomised Controlled Trial of an Ion-exchange Water Softener for the Prevention of Atopic Eczema in Neonates, With an Embedded Mechanistic Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atopic Eczema
Keywords: Water hardness
Atopic eczema prevention
Skin barrier function
Skin microbiome
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Guy's and St Thomas' NHS Foundation Trust
name: University of Nottingham
name: University of Sheffield
name: Imperial College London
name: University of Amsterdam
name: University of Dundee
First posted: 2017-09-01
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: An outcome assessor-blinded pilot randomised controlled trial of an ion-exchange water softener for the prevention of atopic eczema in neonates, with an embedded mechanistic study

Detailed description: A 6-month parallel group assessor-blinded pilot randomised controlled trial of an ion-exchange water softener for the prevention of eczema in neonates, with an embedded mechanistic study.

The overall rationale is that by installing a domestic water softener around the time of birth, the infant will be exposed to softened water rather than hard water for bathing and that this will be less irritating to the skin than hard water and so associated with a lower risk of eczema development. The primary objective is to determine the feasibility of conducting a subsequent definitive RCT that will investigate whether installation of a domestic water softener around the time of birth can prevent eczema in high-risk babies. The secondary objective is to explore the likely mechanisms by which water softeners might prevent eczema.

Eligibility criteria: Inclusion Criteria:

* Participant (i.e. the neonate) must have a parent or sibling with a history of doctor-diagnosed atopy (i.e. at least one of: eczema, asthma, hayfever)
* Mother aged ≥18 years of age at enrolment
* Baby \<36 weeks gestation at screening
* Informed consent from the mother on behalf of the participant
* Mother has the ability to understand English
* Live in a hard water area (\>250 mg/L Calcium Carbonate)
* Consent of landlord for installation on water softener (if appropriate)
* Occupy a property appropriate for installation of a water softener

Exclusion Criteria:

* Preterm birth (defined as birth prior to 37 weeks gestation)
* Significant inflammatory skin disease at birth not including seborrheic dermatitis ("cradle cap")
* Sibling (including twin) previously randomised to this trial. If multiple birth, the first child will be randomised into the trial.
* The child is to be fostered/adopted
* Any immunodeficiency disorder or severe genetic skin disorder
* Child has any other serious health issue which, at parent or investigator discretion, would make it difficult for the family to take part in the trial.
* Planned stays away from home for a continuous period of more than 2 weeks or a total of 1 month out of the 6 month follow up period
* Water softening or filtration device already installed
* Concurrent enrolment in any other skin-related intervention study
* Other medical condition that in the opinion of the CI could interfere with the conduct of the trial

Primary outcomes:
measure: Proportion of eligible families screened who are willing and able to be randomised.
timeFrame: Before birth
Secondary outcomes:
measure: Proportion of pregnant women approached who agree to be screened
timeFrame: Before birth
measure: Proportion of families eligible on screening that cannot have a water softener installed (e.g. due to landlord or local authority refusal, technical (plumbing) reasons)
timeFrame: Before birth
measure: Proportion of families randomised that withdraw due to infant ineligibility
timeFrame: Baseline (birth)
measure: Proportion of families in intervention arm who found the intervention acceptable
timeFrame: End of follow up (6 months of age)
measure: Proportion of participants in control arm that become exposed to softened water
timeFrame: End of follow up (6 months of age)
measure: Proportion of participants that have the water softening unit removed or disabled prior to end of follow up
timeFrame: End of follow up (6 months of age)
measure: Proportion of participants with visible eczema status (yes/no) recorded
timeFrame: Baseline, 4 weeks, 3 and 6 months
measure: Proportion of water samples with hardness >20 mg/L calcium carbonate
timeFrame: Between installation and end of follow up
measure: Proportion of participants that withdraw from the trial prior to end of follow up
timeFrame: From randomisation until end of follow up
measure: Median number of nights spent away from the participant's main home during follow up
timeFrame: From birth until end of follow up (6 months of age)
measure: Proportion of clinical outcome assessments that have remained blinded
timeFrame: at 4 weeks, 3 & 6 months
measure: Proportion with patient-reported, doctor-diagnosed eczema
timeFrame: by 6 months of age
measure: Proportion with visible eczema according to the UK diagnostic criteria-based photographic protocol
timeFrame: 4 weeks, 3 & 6 months
measure: Severity of eczema (if present) using Eczema Area and Severity Index (EASI)
timeFrame: 4 weeks, 3 & 6 months
measure: Patient-reported eczema symptoms (Patient-Orientated Eczema Measure - POEM)
timeFrame: Monthly from 4 weeks to 6 months of age
measure: Time to onset of patient-reported doctor-diagnosed eczema
timeFrame: from birth to end of follow up (6 months of age)
Other outcomes:
measure: Transepidermal water loss (TEWL)
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Cutaneous cytokine profiles
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Natural moisturising factor (NMF) levels
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Shannon Diversity Index and other skin and respiratory microbiota parameters
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Proportion with filaggrin null mutations
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Effect of filaggrin (FLG) gene mutation status on TEWL, cytokine levels, NMF levels and skin microbiota diversity
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Median domestic water hardness level (calcium carbonate concentration)
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
measure: Skin hydration
timeFrame: at birth, 4 weeks, 3 & 6 months oif age
Locations:
city: London
country: United Kingdom
facility: St Thomas' Hospital
Study officials:
affiliation: King's College London
name: Carsten Flohr, PhD, FRCPCH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jabbar-Lopez ZK, Ezzamouri B, Briley A, Greenblatt D, Gurung N, Chalmers JR, Thomas KS, Frost T, Kezic S, Common JEA, Danby S, Cork MJ, Peacock JL, Flohr C. Randomized controlled pilot trial with ion-exchange water softeners to prevent eczema (SOFTER trial). Clin Exp Allergy. 2022 Mar;52(3):405-415. doi: 10.1111/cea.14071. Epub 2021 Dec 12.
citation: Laughter MR, Maymone MBC, Mashayekhi S, Arents BWM, Karimkhani C, Langan SM, Dellavalle RP, Flohr C. The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017. Br J Dermatol. 2021 Feb;184(2):304-309. doi: 10.1111/bjd.19580. Epub 2020 Nov 29.
citation: Jabbar-Lopez ZK, Gurung N, Greenblatt D, Briley A, Chalmers JR, Thomas KS, Frost T, Kezic S, Common JEA, Kong HH, Segre JA, Danby S, Cork MJ, Peacock JL, Flohr C. Protocol for an outcome assessor-blinded pilot randomised controlled trial of an ion-exchange water softener for the prevention of atopic eczema in neonates, with an embedded mechanistic study: the Softened Water for Eczema Prevention (SOFTER) trial. BMJ Open. 2019 Aug 20;9(8):e027168. doi: 10.1136/bmjopen-2018-027168.