Softened Water for Eczema Prevention Pilot Trial (SOFTER)

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

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 Overview

• Status: Unknown
• Conditions: Atopic Eczema
• Intervention / Treatment: Device: Domestic ion-exchange water softener

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • St Thomas' Hospital
    • Contact: Zarif Jabbar-Lopez, MPH MRCP; Phone Number: 57716 02071887188; Email: zarif.jabbar-lopez@kcl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Domestic ion-exchange water softener; The intervention group will have a domestic ion-exchange water softener installed prior to birth.	Device: Domestic ion-exchange water softener; Ion-exchange water softeners exchange calcium and magnesium, amongst other divalent cations, for monovalent sodium cations using a polystyrene resin. The sodium ions come from sodium chloride (common salt). The salt needs to be topped up every 3-4 weeks and sufficient quantities of block salt will be supplied to participants. The water softener used in this study does not require electricity and has two cylinders of resin which are used alternately. A control valve alternates the flow between the two cylinders and ensures a constant supply of regenerated resin. Ion-exchange water softeners typically reduce downstream water hardness to close to zero.
No Intervention: Usual hard water supply; The control group will receive their usual domestic water supply.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eligible families screened who are willing and able to be randomised.	This is key to the determination of the likely success of a future, large-scale definitive randomised controlled trial (RCT).	Before birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of pregnant women approached who agree to be screened		Before birth
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)		Before birth
Proportion of families randomised that withdraw due to infant ineligibility		Baseline (birth)
Proportion of families in intervention arm who found the intervention acceptable		End of follow up (6 months of age)
Proportion of participants in control arm that become exposed to softened water	(e.g. by moving to a new home in a soft water area, or moving to a home with an active water softener installed, before the end of follow up)	End of follow up (6 months of age)
Proportion of participants that have the water softening unit removed or disabled prior to end of follow up		End of follow up (6 months of age)
Proportion of participants with visible eczema status (yes/no) recorded	According to UK diagnostic criteria-based photographic protocol	Baseline, 4 weeks, 3 and 6 months
Proportion of water samples with hardness >20 mg/L calcium carbonate	Would suggest failure of the water softening device	Between installation and end of follow up
Proportion of participants that withdraw from the trial prior to end of follow up		From randomisation until end of follow up
Median number of nights spent away from the participant's main home during follow up		From birth until end of follow up (6 months of age)
Proportion of clinical outcome assessments that have remained blinded		at 4 weeks, 3 & 6 months
Proportion with patient-reported, doctor-diagnosed eczema		by 6 months of age
Proportion with visible eczema according to the UK diagnostic criteria-based photographic protocol		4 weeks, 3 & 6 months
Severity of eczema (if present) using Eczema Area and Severity Index (EASI)		4 weeks, 3 & 6 months
Patient-reported eczema symptoms (Patient-Orientated Eczema Measure - POEM)		Monthly from 4 weeks to 6 months of age
Time to onset of patient-reported doctor-diagnosed eczema		from birth to end of follow up (6 months of age)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transepidermal water loss (TEWL)		at birth, 4 weeks, 3 & 6 months oif age
Cutaneous cytokine profiles	e.g. interleukin-1 levels	at birth, 4 weeks, 3 & 6 months oif age
Natural moisturising factor (NMF) levels		at birth, 4 weeks, 3 & 6 months oif age
Shannon Diversity Index and other skin and respiratory microbiota parameters		at birth, 4 weeks, 3 & 6 months oif age
Proportion with filaggrin null mutations		at birth, 4 weeks, 3 & 6 months oif age
Effect of filaggrin (FLG) gene mutation status on TEWL, cytokine levels, NMF levels and skin microbiota diversity		at birth, 4 weeks, 3 & 6 months oif age
Median domestic water hardness level (calcium carbonate concentration)		at birth, 4 weeks, 3 & 6 months oif age
Skin hydration		at birth, 4 weeks, 3 & 6 months oif age

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: University of Nottingham; Imperial College London; University of Sheffield; Guy's and St Thomas' NHS Foundation Trust; University of Amsterdam; University of Dundee
• Investigators: Principal Investigator: Carsten Flohr, PhD, FRCPCH, King's College London

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: August 31, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 15, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Skin microbiome; Water hardness; Atopic eczema prevention; Skin barrier function
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Dermatitis; Skin Diseases, Eczematous; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: IRAS 233005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plans to share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No