<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/NCT03763630</url>
  </required_header>
  <id_info>
    <org_study_id>Southampton CHI0808</org_study_id>
    <nct_id>NCT03763630</nct_id>
  </id_info>
  <brief_title>MAPS &amp; ITEC Cohorts: 6-8 Years Follow-up</brief_title>
  <official_title>Primary Prevention of Atopy and Asthma With House Dust Mite Sublingual Immunotherapy: 6-8 Years Follow up</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southampton</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Isle of Wight NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southampton</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>
      This study represents the follow-up, age 6-8 years, of children recruited at birth into two&#xD;
      cohorts. The first cohort, the Mite Allergen Prevention Study (MAPS) was a double-blind,&#xD;
      randomized controlled trial of the use of house dust-mite immunotherapy in the primary&#xD;
      prevention of atopy and asthma. The Immune Tolerance in Early Childhood (ITEC) cohort is a&#xD;
      separate observational cohort following up infants at high risk of atopy and correlating&#xD;
      atopic disease development with epigenetic markers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is an epidemic of allergic disease in childhood and current preventative strategies&#xD;
      have failed to demonstrate effectiveness outside of isolated trials. In a previous study, the&#xD;
      efficacy of sublingual immunotherapy (SLIT) with house dust mite in preventing the&#xD;
      development of allergic sensitisation in infants was assessed. The long term objective was to&#xD;
      assess the effect of the intervention on the subsequent development of asthma. The hypothesis&#xD;
      is that high dose oral immunotherapy will induce immune tolerance and reduce development of&#xD;
      allergic sensitisation and later clinical asthma and allergy. A total of 111 infants at high&#xD;
      risk of allergy (with ≥2 first degree relatives affected by asthma or allergy) but with no&#xD;
      evidence of allergic sensitisation at recruitment were recruited. These infants were&#xD;
      randomised at 6 months of age to receive a year of active HDM (House dust-mite) allergen&#xD;
      extract delivered as SLIT or placebo intervention. At 18 months of age, there was a&#xD;
      significant reduction in cumulative allergic sensitisation in the SLIT intervention group and&#xD;
      a trend for reduction in allergic symptoms. They have also been followed up at 3 years of&#xD;
      age. The data currently being analysed.&#xD;
&#xD;
      Additionally, an observational cohort (Immune Tolerance in Early Childhood, ITEC) was&#xD;
      recruited at birth with the same inclusion criteria as the interventional one and assessed in&#xD;
      the same way up to 3 years. This cohort has provided additional control data and samples to&#xD;
      utilise in the analyses.&#xD;
&#xD;
      This proposed study is the 6-8 year follow up of these interventional and observational&#xD;
      cohorts. The aim of the 6-8 year assessment is to assess the efficacy of prophylactic oral&#xD;
      immunotherapy with HDM allergen in preventing the later development of asthma. The hypothesis&#xD;
      is that high dose oral immunotherapy will induce immune tolerance and reduce development of&#xD;
      allergic sensitisation and later clinical asthma and allergy. Participants will be assessed&#xD;
      6-8 years after finishing the intervention. The assessment will include a questionnaire, skin&#xD;
      prick testing to the common aeroallergens and food allergens and lung function. Families and&#xD;
      study investigators will both be blinded to participants' original treatment allocations. An&#xD;
      additional aim is to investigate the epigenetic and immune mechanisms involved in the&#xD;
      development of asthma and allergy and how allergen immunotherapy influence this process.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">January 15, 2019</completion_date>
  <primary_completion_date type="Actual">December 5, 2018</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Asthma - parental questionnaire</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of clinical asthma, as assessed by parental questionnaire, at age 6 years between control and intervention groups. Clinical asthma will be defined as either doctor diagnosed asthma or presence of wheeze and asthma medication use within the past year.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Asthma- spirometry with reversibility</measure>
    <time_frame>6 years</time_frame>
    <description>Comparison of clinical asthma, as assessed by lung function testing, at age 6 years between control and intervention groups. Clinical asthma will be defined as in improvement in FEV1 (Forced Expiratory Volume in 1 second) of 12% or more following administration of salbutamol inhaler (bronchodilator).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bronchial hyper-responsiveness</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of bronchial hyperresponsiveness, as determined by methacholine bronchial allergen challenge, at age 6 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma comparison</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of asthma, as defined by wheeze plus bronchial hyperreactivity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway inflammation level- exhaled nitric oxide measurement</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of airway inflammation level, as assessed by exhaled nitric oxide, between placebo and intervention group age 6 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative sensitization</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of cumulative sensitization to one or more of 6 common allergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative aeroallergen sensitization</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of cumulative sensitization to one or more of 6 common aeroallergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>House dust-mite sensitization</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of sensitization to house dust mite, as assessed by skin prick test, at 18 months, 3 years and 6-8 years of age between control and intervention groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical atopic disease- parental questionnaire</measure>
    <time_frame>Age 6 years</time_frame>
    <description>Comparison of clinical allergic diseases/symptoms (atopic eczema, wheeze, allergic rhinitis, food allergy) at 18 months, 3 years and 6 years of age between control and intervention groups. Presence of clinical disease evaluated through parental questionnaires</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">263</enrollment>
  <condition>Immunotherapy</condition>
  <condition>Allergy and Immunology</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Intervention arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>House dust-mite SLIT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation cohort</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>ITEC observational cohort, no intervention administered</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>House dust-mite SLIT</intervention_name>
    <description>received 2000 standard treatment units of glycerinated HDM allergen extract (ALK-AbellÓ) per day. Normal saline was administered to the placebo group. 11 µg of HDM allergen (equal parts of Dermatophagoides pteronyssinus and Dermatophagoides farinae) administered twice daily as oral drops.</description>
    <arm_group_label>Intervention arm</arm_group_label>
    <other_name>glycerinated HDM allergen extract (ALK-AbellÓ)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>Normal saline administered in same frequency and manner as intervention</description>
    <arm_group_label>Control arm</arm_group_label>
    <other_name>Normal saline placebo control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        •Inclusion in original study cohorts at birth&#xD;
&#xD;
        •≥2 first-degree relatives with allergic disease (food allergy, asthma, eczema,&#xD;
        rhinoconjunctivitis)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not included in the original study cohorts&#xD;
&#xD;
          -  Skin-prick test positive to any allergen (HDM, cat, grass pollen, peanut, egg and&#xD;
             milk) age 5 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Months</minimum_age>
    <maximum_age>9 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Graham Roberts, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southampton</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>David Hyde Asthma and Allergy Centre</name>
      <address>
        <city>Newport</city>
        <state>Isle Of White</state>
        <zip>PO30 5TG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Zolkipli Z, Roberts G, Cornelius V, Clayton B, Pearson S, Michaelis L, Djukanovic R, Kurukulaaratchy R, Arshad SH. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. J Allergy Clin Immunol. 2015 Dec;136(6):1541-1547.e11. doi: 10.1016/j.jaci.2015.04.045. Epub 2015 Jun 12.</citation>
    <PMID>26073754</PMID>
  </results_reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>October 1, 2021</last_update_submitted>
  <last_update_submitted_qc>October 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atopy</keyword>
  <keyword>Early childhood</keyword>
  <keyword>House Dust-mite</keyword>
  <keyword>Sublingual immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03763630
org study id: Southampton CHI0808
nct id: NCT03763630
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study represents the follow-up, age 6-8 years, of children recruited at birth into two
      cohorts. The first cohort, the Mite Allergen Prevention Study (MAPS) was a double-blind,
      randomized controlled trial of the use of house dust-mite immunotherapy in the primary
      prevention of atopy and asthma. The Immune Tolerance in Early Childhood (ITEC) cohort is a
      separate observational cohort following up infants at high risk of atopy and correlating
      atopic disease development with epigenetic markers.
There is an epidemic of allergic disease in childhood and current preventative strategies
      have failed to demonstrate effectiveness outside of isolated trials. In a previous study, the
      efficacy of sublingual immunotherapy (SLIT) with house dust mite in preventing the
      development of allergic sensitisation in infants was assessed. The long term objective was to
      assess the effect of the intervention on the subsequent development of asthma. The hypothesis
      is that high dose oral immunotherapy will induce immune tolerance and reduce development of
      allergic sensitisation and later clinical asthma and allergy. A total of 111 infants at high
      risk of allergy (with ≥2 first degree relatives affected by asthma or allergy) but with no
      evidence of allergic sensitisation at recruitment were recruited. These infants were
      randomised at 6 months of age to receive a year of active HDM (House dust-mite) allergen
      extract delivered as SLIT or placebo intervention. At 18 months of age, there was a
      significant reduction in cumulative allergic sensitisation in the SLIT intervention group and
      a trend for reduction in allergic symptoms. They have also been followed up at 3 years of
      age. The data currently being analysed.

      Additionally, an observational cohort (Immune Tolerance in Early Childhood, ITEC) was
      recruited at birth with the same inclusion criteria as the interventional one and assessed in
      the same way up to 3 years. This cohort has provided additional control data and samples to
      utilise in the analyses.

      This proposed study is the 6-8 year follow up of these interventional and observational
      cohorts. The aim of the 6-8 year assessment is to assess the efficacy of prophylactic oral
      immunotherapy with HDM allergen in preventing the later development of asthma. The hypothesis
      is that high dose oral immunotherapy will induce immune tolerance and reduce development of
      allergic sensitisation and later clinical asthma and allergy. Participants will be assessed
      6-8 years after finishing the intervention. The assessment will include a questionnaire, skin
      prick testing to the common aeroallergens and food allergens and lung function. Families and
      study investigators will both be blinded to participants' original treatment allocations. An
      additional aim is to investigate the epigenetic and immune mechanisms involved in the
      development of asthma and allergy and how allergen immunotherapy influence this process.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Clinical Asthma - parental questionnaire
time frame: Age 6 years
description: Comparison of clinical asthma, as assessed by parental questionnaire, at age 6 years between control and intervention groups. Clinical asthma will be defined as either doctor diagnosed asthma or presence of wheeze and asthma medication use within the past year.
measure: Clinical Asthma- spirometry with reversibility
time frame: 6 years
description: Comparison of clinical asthma, as assessed by lung function testing, at age 6 years between control and intervention groups. Clinical asthma will be defined as in improvement in FEV1 (Forced Expiratory Volume in 1 second) of 12% or more following administration of salbutamol inhaler (bronchodilator).
measure: Bronchial hyper-responsiveness
time frame: Age 6 years
description: Comparison of bronchial hyperresponsiveness, as determined by methacholine bronchial allergen challenge, at age 6 years.
measure: Asthma comparison
time frame: Age 6 years
description: Comparison of asthma, as defined by wheeze plus bronchial hyperreactivity
measure: Airway inflammation level- exhaled nitric oxide measurement
time frame: Age 6 years
description: Comparison of airway inflammation level, as assessed by exhaled nitric oxide, between placebo and intervention group age 6 years
measure: Cumulative sensitization
time frame: Age 6 years
description: Comparison of cumulative sensitization to one or more of 6 common allergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.
measure: Cumulative aeroallergen sensitization
time frame: Age 6 years
description: Comparison of cumulative sensitization to one or more of 6 common aeroallergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.
measure: House dust-mite sensitization
time frame: Age 6 years
description: Comparison of sensitization to house dust mite, as assessed by skin prick test, at 18 months, 3 years and 6-8 years of age between control and intervention groups.
measure: Clinical atopic disease- parental questionnaire
time frame: Age 6 years
description: Comparison of clinical allergic diseases/symptoms (atopic eczema, wheeze, allergic rhinitis, food allergy) at 18 months, 3 years and 6 years of age between control and intervention groups. Presence of clinical disease evaluated through parental questionnaires
arm group label: Intervention arm
arm group type: Active Comparator
description: House dust-mite SLIT
arm group label: Control arm
arm group type: Placebo Comparator
description: Normal saline
arm group label: Observation cohort
arm group type: No Intervention
description: ITEC observational cohort, no intervention administered
intervention type: Drug
intervention name: House dust-mite SLIT
description: received 2000 standard treatment units of glycerinated HDM allergen extract (ALK-AbellÓ) per day. Normal saline was administered to the placebo group. 11 µg of HDM allergen (equal parts of Dermatophagoides pteronyssinus and Dermatophagoides farinae) administered twice daily as oral drops.
arm group label: Intervention arm
other name: glycerinated HDM allergen extract (ALK-AbellÓ)
intervention type: Drug
intervention name: Normal saline
description: Normal saline administered in same frequency and manner as intervention
arm group label: Control arm
other name: Normal saline placebo control
criteria: 
gender: All
minimum age: 5 Months
maximum age: 9 Months
healthy volunteers: No
last name: Graham Roberts, Prof
role: Principal Investigator
affiliation: University of Southampton
facility: 
facility: 
country: United Kingdom
citation: Zolkipli Z, Roberts G, Cornelius V, Clayton B, Pearson S, Michaelis L, Djukanovic R, Kurukulaaratchy R, Arshad SH. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. J Allergy Clin Immunol. 2015 Dec;136(6):1541-1547.e11. doi: 10.1016/j.jaci.2015.04.045. Epub 2015 Jun 12.
PMID: 26073754
responsible party type: Sponsor
mesh term: Asthma
sharing ipd: No