<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03270566</url>
  </required_header>
  <id_info>
    <org_study_id>IRAS 233005</org_study_id>
    <nct_id>NCT03270566</nct_id>
  </id_info>
  <brief_title>Softened Water for Eczema Prevention Pilot Trial</brief_title>
  <acronym>SOFTER</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Sheffield</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Amsterdam</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Dundee</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An outcome assessor-blinded pilot randomised controlled trial of an ion-exchange water&#xD;
      softener for the prevention of atopic eczema in neonates, with an embedded mechanistic study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A 6-month parallel group assessor-blinded pilot randomised controlled trial of an&#xD;
      ion-exchange water softener for the prevention of eczema in neonates, with an embedded&#xD;
      mechanistic study.&#xD;
&#xD;
      The overall rationale is that by installing a domestic water softener around the time of&#xD;
      birth, the infant will be exposed to softened water rather than hard water for bathing and&#xD;
      that this will be less irritating to the skin than hard water and so associated with a lower&#xD;
      risk of eczema development. The primary objective is to determine the feasibility of&#xD;
      conducting a subsequent definitive RCT that will investigate whether installation of a&#xD;
      domestic water softener around the time of birth can prevent eczema in high-risk babies. The&#xD;
      secondary objective is to explore the likely mechanisms by which water softeners might&#xD;
      prevent eczema.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 12, 2018</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of eligible families screened who are willing and able to be randomised.</measure>
    <time_frame>Before birth</time_frame>
    <description>This is key to the determination of the likely success of a future, large-scale definitive randomised controlled trial (RCT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of pregnant women approached who agree to be screened</measure>
    <time_frame>Before birth</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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)</measure>
    <time_frame>Before birth</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of families randomised that withdraw due to infant ineligibility</measure>
    <time_frame>Baseline (birth)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of families in intervention arm who found the intervention acceptable</measure>
    <time_frame>End of follow up (6 months of age)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants in control arm that become exposed to softened water</measure>
    <time_frame>End of follow up (6 months of age)</time_frame>
    <description>(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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants that have the water softening unit removed or disabled prior to end of follow up</measure>
    <time_frame>End of follow up (6 months of age)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with visible eczema status (yes/no) recorded</measure>
    <time_frame>Baseline, 4 weeks, 3 and 6 months</time_frame>
    <description>According to UK diagnostic criteria-based photographic protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of water samples with hardness &gt;20 mg/L calcium carbonate</measure>
    <time_frame>Between installation and end of follow up</time_frame>
    <description>Would suggest failure of the water softening device</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants that withdraw from the trial prior to end of follow up</measure>
    <time_frame>From randomisation until end of follow up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median number of nights spent away from the participant's main home during follow up</measure>
    <time_frame>From birth until end of follow up (6 months of age)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of clinical outcome assessments that have remained blinded</measure>
    <time_frame>at 4 weeks, 3 &amp; 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion with patient-reported, doctor-diagnosed eczema</measure>
    <time_frame>by 6 months of age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion with visible eczema according to the UK diagnostic criteria-based photographic protocol</measure>
    <time_frame>4 weeks, 3 &amp; 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of eczema (if present) using Eczema Area and Severity Index (EASI)</measure>
    <time_frame>4 weeks, 3 &amp; 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported eczema symptoms (Patient-Orientated Eczema Measure - POEM)</measure>
    <time_frame>Monthly from 4 weeks to 6 months of age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to onset of patient-reported doctor-diagnosed eczema</measure>
    <time_frame>from birth to end of follow up (6 months of age)</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Transepidermal water loss (TEWL)</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Cutaneous cytokine profiles</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
    <description>e.g. interleukin-1 levels</description>
  </other_outcome>
  <other_outcome>
    <measure>Natural moisturising factor (NMF) levels</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Shannon Diversity Index and other skin and respiratory microbiota parameters</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Proportion with filaggrin null mutations</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect of filaggrin (FLG) gene mutation status on TEWL, cytokine levels, NMF levels and skin microbiota diversity</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Median domestic water hardness level (calcium carbonate concentration)</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Skin hydration</measure>
    <time_frame>at birth, 4 weeks, 3 &amp; 6 months oif age</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Atopic Eczema</condition>
  <arm_group>
    <arm_group_label>Domestic ion-exchange water softener</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention group will have a domestic ion-exchange water softener installed prior to birth.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual hard water supply</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group will receive their usual domestic water supply.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Domestic ion-exchange water softener</intervention_name>
    <description>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.</description>
    <arm_group_label>Domestic ion-exchange water softener</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant (i.e. the neonate) must have a parent or sibling with a history of&#xD;
             doctor-diagnosed atopy (i.e. at least one of: eczema, asthma, hayfever)&#xD;
&#xD;
          -  Mother aged ≥18 years of age at enrolment&#xD;
&#xD;
          -  Baby &lt;36 weeks gestation at screening&#xD;
&#xD;
          -  Informed consent from the mother on behalf of the participant&#xD;
&#xD;
          -  Mother has the ability to understand English&#xD;
&#xD;
          -  Live in a hard water area (&gt;250 mg/L Calcium Carbonate)&#xD;
&#xD;
          -  Consent of landlord for installation on water softener (if appropriate)&#xD;
&#xD;
          -  Occupy a property appropriate for installation of a water softener&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preterm birth (defined as birth prior to 37 weeks gestation)&#xD;
&#xD;
          -  Significant inflammatory skin disease at birth not including seborrheic dermatitis&#xD;
             (&quot;cradle cap&quot;)&#xD;
&#xD;
          -  Sibling (including twin) previously randomised to this trial. If multiple birth, the&#xD;
             first child will be randomised into the trial.&#xD;
&#xD;
          -  The child is to be fostered/adopted&#xD;
&#xD;
          -  Any immunodeficiency disorder or severe genetic skin disorder&#xD;
&#xD;
          -  Child has any other serious health issue which, at parent or investigator discretion,&#xD;
             would make it difficult for the family to take part in the trial.&#xD;
&#xD;
          -  Planned stays away from home for a continuous period of more than 2 weeks or a total&#xD;
             of 1 month out of the 6 month follow up period&#xD;
&#xD;
          -  Water softening or filtration device already installed&#xD;
&#xD;
          -  Concurrent enrolment in any other skin-related intervention study&#xD;
&#xD;
          -  Other medical condition that in the opinion of the CI could interfere with the conduct&#xD;
             of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carsten Flohr, PhD, FRCPCH</last_name>
    <role>Principal Investigator</role>
    <affiliation>King's College London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zarif Jabbar-Lopez, MPH, MRCP</last_name>
    <phone>020 7188 7188</phone>
    <phone_ext>57716</phone_ext>
    <email>zarif.jabbar-lopez@kcl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>St Thomas' Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zarif Jabbar-Lopez, MPH MRCP</last_name>
      <phone>02071887188</phone>
      <phone_ext>57716</phone_ext>
      <email>zarif.jabbar-lopez@kcl.ac.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>February 15, 2018</last_update_submitted>
  <last_update_submitted_qc>February 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Water hardness</keyword>
  <keyword>Atopic eczema prevention</keyword>
  <keyword>Skin barrier function</keyword>
  <keyword>Skin microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plans to share IPD</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03270566
org study id: IRAS 233005
nct id: NCT03270566
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Proportion of eligible families screened who are willing and able to be randomised.
time frame: Before birth
description: This is key to the determination of the likely success of a future, large-scale definitive randomised controlled trial (RCT).
measure: Proportion of pregnant women approached who agree to be screened
time frame: 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)
time frame: Before birth
measure: Proportion of families randomised that withdraw due to infant ineligibility
time frame: Baseline (birth)
measure: Proportion of families in intervention arm who found the intervention acceptable
time frame: End of follow up (6 months of age)
measure: Proportion of participants in control arm that become exposed to softened water
time frame: End of follow up (6 months of age)
description: (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)
measure: Proportion of participants that have the water softening unit removed or disabled prior to end of follow up
time frame: End of follow up (6 months of age)
measure: Proportion of participants with visible eczema status (yes/no) recorded
time frame: Baseline, 4 weeks, 3 and 6 months
description: According to UK diagnostic criteria-based photographic protocol
measure: Proportion of water samples with hardness >20 mg/L calcium carbonate
time frame: Between installation and end of follow up
description: Would suggest failure of the water softening device
measure: Proportion of participants that withdraw from the trial prior to end of follow up
time frame: From randomisation until end of follow up
measure: Median number of nights spent away from the participant's main home during follow up
time frame: From birth until end of follow up (6 months of age)
measure: Proportion of clinical outcome assessments that have remained blinded
time frame: at 4 weeks, 3 & 6 months
measure: Proportion with patient-reported, doctor-diagnosed eczema
time frame: by 6 months of age
measure: Proportion with visible eczema according to the UK diagnostic criteria-based photographic protocol
time frame: 4 weeks, 3 & 6 months
measure: Severity of eczema (if present) using Eczema Area and Severity Index (EASI)
time frame: 4 weeks, 3 & 6 months
measure: Patient-reported eczema symptoms (Patient-Orientated Eczema Measure - POEM)
time frame: Monthly from 4 weeks to 6 months of age
measure: Time to onset of patient-reported doctor-diagnosed eczema
time frame: from birth to end of follow up (6 months of age)
measure: Transepidermal water loss (TEWL)
time frame: at birth, 4 weeks, 3 & 6 months oif age
measure: Cutaneous cytokine profiles
time frame: at birth, 4 weeks, 3 & 6 months oif age
description: e.g. interleukin-1 levels
measure: Natural moisturising factor (NMF) levels
time frame: at birth, 4 weeks, 3 & 6 months oif age
measure: Shannon Diversity Index and other skin and respiratory microbiota parameters
time frame: at birth, 4 weeks, 3 & 6 months oif age
measure: Proportion with filaggrin null mutations
time frame: 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
time frame: at birth, 4 weeks, 3 & 6 months oif age
measure: Median domestic water hardness level (calcium carbonate concentration)
time frame: at birth, 4 weeks, 3 & 6 months oif age
measure: Skin hydration
time frame: at birth, 4 weeks, 3 & 6 months oif age
arm group label: Domestic ion-exchange water softener
arm group type: Experimental
description: The intervention group will have a domestic ion-exchange water softener installed prior to birth.
arm group label: Usual hard water supply
arm group type: No Intervention
description: The control group will receive their usual domestic water supply.
intervention type: Device
intervention name: Domestic ion-exchange water softener
description: 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.
arm group label: Domestic ion-exchange water softener
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Carsten Flohr, PhD, FRCPCH
role: Principal Investigator
affiliation: King's College London
last name: Zarif Jabbar-Lopez, MPH, MRCP
phone: 020 7188 7188
phone ext: 57716
email: zarif.jabbar-lopez@kcl.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Eczema
sharing ipd: No
ipd description: No plans to share IPD