<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/NCT03819556</url>
  </required_header>
  <id_info>
    <org_study_id>F07</org_study_id>
    <nct_id>NCT03819556</nct_id>
  </id_info>
  <brief_title>Swedish Study of Immunotherapy for Milk Allergy in Children</brief_title>
  <acronym>SWITCH</acronym>
  <official_title>Swedish Study of Immunotherapy for Milk Allergy in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Umeå University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Umeå University</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 trial is a two-armed open randomized controlled trial in children aged 5-15 years with&#xD;
      challenge proven Immunoglobulin E (IgE)-associated milk allergy.The purpose is to determine&#xD;
      if oral immunotherapy with milk can induce tolerance to milk. The active intervention is&#xD;
      intake of increasing amounts of fresh milk for six months followed by three years of&#xD;
      maintenance treatment with milk. The control group continues their elimination (milk free)&#xD;
      diet. The trial will recruit patients at ten pediatric departments in Sweden, coordinated by&#xD;
      Umeå University. The primary outcome is milk tolerance (defined as a negative double-blind&#xD;
      placebo-controlled milk challenge) at trial completion 3.5 years after start of treatment.&#xD;
      Secondary outcomes include allergic symptoms during treatment documented as certain allergic&#xD;
      manifestations, changes in immunological and microbial biomarkers, quality of life and&#xD;
      nutritional status.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The underlying hypothesis is that exposure to milk in a controlled way can be delivered&#xD;
      safely and induce tolerance to milk.The aim of this trial is to evaluate a specific protocol&#xD;
      for oral milk intake to achieve sustainable tolerance.&#xD;
&#xD;
      Before randomization all patients are tested for milk allergy using a double-blind&#xD;
      placebo-controlled milk challenge and baseline laboratory analyses (specific IgE). Patients&#xD;
      with confirmed, challenge-proven milk allergy are randomized to oral immunotherapy (active&#xD;
      group) or milk-free diet (control group).The active group will receive a stepwise increase in&#xD;
      oral milk intake. The increased dose will be given in hospital outpatient clinics by&#xD;
      experienced study staff following a standard protocol. All other doses are given att home&#xD;
      where the patients have adrenaline ready to use. When the patient has reached a daily intake&#xD;
      of 100 ml of milk without serious allergic reactions they will be maintained on this dosis&#xD;
      for three years. At this stage (after finished dose escalation or after six months for the&#xD;
      control group) the patients will be tested for the second set of laboratory analyses.&#xD;
&#xD;
      During maintenance, the patients in the active group are encouraged not to avoid milk protein&#xD;
      and instead eat milk-containing food when it is offered. Patients in the control group&#xD;
      receive standard care with exclusion of milk from their diet for the whole trial duration.&#xD;
&#xD;
      After three years of maintenance therapy for the active group, both groups avoid milk for one&#xD;
      week and then undergo a double-blind placebo-controlled milk challenge and the third set of&#xD;
      samples for immunological comparison.&#xD;
&#xD;
      The immunological markers are Immunoglobulins (E, G4, A), microbiota and basophilic&#xD;
      activation. All patients are also evaluated for quality of life and nutritional status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 20, 2018</start_date>
  <completion_date type="Anticipated">October 20, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 20, 2024</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>
    <intervention_model_description>Open randomized interventional study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants that achieve tolerance to milk</measure>
    <time_frame>3.5 years after start of treatment</time_frame>
    <description>Tolerance is defined as absence of IgE-mediated allergic symptoms connected to a double-blind placebo-controlled milk challenge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in level of basophil activation (CD sens) in blood</measure>
    <time_frame>At baseline, after 6 months, after 3.5 years</time_frame>
    <description>Level of basophil activation at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Quality Of Life: FAQLQ-PF</measure>
    <time_frame>At baseline, after 3.5 years</time_frame>
    <description>Quality Of Life, reported by questionnaire (FAQLQ-PF) after completion of the intervention (3.5 years) compared to pre-trial baseline level. The scale used is Emotional Impact, Food Related anxiety and Dietary Limitations. Each question of the FAQLQ is answered on a 7-point scale. Total FAQLQ scores and domain scores are calculated by dividing the sum of completed items by the number of completed items. Total FaQLQ and domain scores range from 1 &quot;no impairment&quot; to 7 &quot;maximal impairment&quot;. Higher values are a worse outcome (low health related quality of life). Subscale is Health related quality of life (HRQoL summary score=(Emotional Impact subscale score + Food Related anxiety subscale score+Dietary Limitations subscale score)/3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in nutritional status</measure>
    <time_frame>At baseline, after 3.5 years</time_frame>
    <description>Body Mass Index (BMI) after completion of the intervention (3.5 years) compared to pre-trial baseline levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of treatment-demanding adverse effects</measure>
    <time_frame>3.5 years</time_frame>
    <description>Number of events with adrenaline injection within 2 hours after a dose of milk (one or two injections) during step-up and maintenance therapy respectively. Number of events with inhalation of bronchodilatator within 2 hours after a dose of milk during step up and maintenance therapy respectively. Number of participants with two or more events with adrenaline injections during step-up and maintenance respectively. Number of participants with two or more events with inhalation of bronchodilatator during step-up and maintenance therapy respectively. Number of participants with no events of adrenaline injections. Number of participants with no events of inhalation with bronchodilatator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in level of IgE milk in blood</measure>
    <time_frame>Baseline, 6 months, 3.5 years</time_frame>
    <description>Level of IgE milk including the components IgE casein, IgE lactoglobulin and lactalbumin at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in level of IgG4 milk in blood</measure>
    <time_frame>Baseline, 6 months, 3.5 years</time_frame>
    <description>Level of IgG4 milk at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in level of IgA in saliva</measure>
    <time_frame>Baseline, 6 months, 3.5 years</time_frame>
    <description>Level of IgA at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in overall microbial composition in stools</measure>
    <time_frame>Baseline, 6 months, 3.5 years</time_frame>
    <description>The overall microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in overall microbial composition in saliva</measure>
    <time_frame>Baseline, 6 months, 3.5 years</time_frame>
    <description>The microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Milk Allergy</condition>
  <arm_group>
    <arm_group_label>Active immunotherapy with milk protein</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily dose fresh milk protein increased in 11 steps</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Diet free from milk protein</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Milk protein in fresh milk</intervention_name>
    <description>Milk protein in increasing doses.</description>
    <arm_group_label>Active immunotherapy with milk protein</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Immunoglobulin E (IgE) milk &gt;0.1 kU/L&#xD;
&#xD;
          -  Allergic reaction within 2 hours after intake of milk protein&#xD;
&#xD;
          -  Age 5-15 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled asthma, &gt;12 % increase in Forced Expiratory Volume in 1 second (FEV1)&#xD;
             after inhaled bronchodilatator and Asthma Control Test (ACT)&lt;20&#xD;
&#xD;
          -  No allergic reaction at a controlled milk challenge&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Severe immune deficiency&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Chronic urticaria&#xD;
&#xD;
          -  Eosinophil esophagitis&#xD;
&#xD;
          -  Pregnancy and breastfeeding&#xD;
&#xD;
          -  Ongoing immunotherapy to one or more allergens&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christina E West, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Umeå University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christina West, Associated professor</last_name>
    <phone>+46 703972792</phone>
    <email>christina.west@umu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Solveig Röisgård</last_name>
    <phone>+46 702791831</phone>
    <email>solveig.roisgard@regionjh.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Solveig Röisgård</name>
      <address>
        <city>Östersund</city>
        <state>Jämtland Härjedalen</state>
        <zip>83183</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Solveig Röisgård, MD</last_name>
      <phone>+46702791831</phone>
      <email>solveig.roisgard@regionjh.se</email>
    </contact>
    <contact_backup>
      <last_name>Christina West, MD, PhD</last_name>
      <phone>+46703972792</phone>
      <email>christina.west@umu.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>April 20, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>May 19, 2020</last_update_submitted>
  <last_update_submitted_qc>May 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Umeå University</investigator_affiliation>
    <investigator_full_name>Christina West</investigator_full_name>
    <investigator_title>Associate professor/Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Cow milk allergy</keyword>
  <keyword>Oral immune therapy</keyword>
  <keyword>Basophil activation test</keyword>
  <keyword>IgE</keyword>
  <keyword>Microbiome</keyword>
  <keyword>Quality of life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Milk Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Caseins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</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/NCT03819556
org study id: F07
nct id: NCT03819556
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This trial is a two-armed open randomized controlled trial in children aged 5-15 years with
      challenge proven Immunoglobulin E (IgE)-associated milk allergy.The purpose is to determine
      if oral immunotherapy with milk can induce tolerance to milk. The active intervention is
      intake of increasing amounts of fresh milk for six months followed by three years of
      maintenance treatment with milk. The control group continues their elimination (milk free)
      diet. The trial will recruit patients at ten pediatric departments in Sweden, coordinated by
      Umeå University. The primary outcome is milk tolerance (defined as a negative double-blind
      placebo-controlled milk challenge) at trial completion 3.5 years after start of treatment.
      Secondary outcomes include allergic symptoms during treatment documented as certain allergic
      manifestations, changes in immunological and microbial biomarkers, quality of life and
      nutritional status.
The underlying hypothesis is that exposure to milk in a controlled way can be delivered
      safely and induce tolerance to milk.The aim of this trial is to evaluate a specific protocol
      for oral milk intake to achieve sustainable tolerance.

      Before randomization all patients are tested for milk allergy using a double-blind
      placebo-controlled milk challenge and baseline laboratory analyses (specific IgE). Patients
      with confirmed, challenge-proven milk allergy are randomized to oral immunotherapy (active
      group) or milk-free diet (control group).The active group will receive a stepwise increase in
      oral milk intake. The increased dose will be given in hospital outpatient clinics by
      experienced study staff following a standard protocol. All other doses are given att home
      where the patients have adrenaline ready to use. When the patient has reached a daily intake
      of 100 ml of milk without serious allergic reactions they will be maintained on this dosis
      for three years. At this stage (after finished dose escalation or after six months for the
      control group) the patients will be tested for the second set of laboratory analyses.

      During maintenance, the patients in the active group are encouraged not to avoid milk protein
      and instead eat milk-containing food when it is offered. Patients in the control group
      receive standard care with exclusion of milk from their diet for the whole trial duration.

      After three years of maintenance therapy for the active group, both groups avoid milk for one
      week and then undergo a double-blind placebo-controlled milk challenge and the third set of
      samples for immunological comparison.

      The immunological markers are Immunoglobulins (E, G4, A), microbiota and basophilic
      activation. All patients are also evaluated for quality of life and nutritional status.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open randomized interventional study
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants that achieve tolerance to milk
time frame: 3.5 years after start of treatment
description: Tolerance is defined as absence of IgE-mediated allergic symptoms connected to a double-blind placebo-controlled milk challenge
measure: Changes in level of basophil activation (CD sens) in blood
time frame: At baseline, after 6 months, after 3.5 years
description: Level of basophil activation at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins
measure: Changes in Quality Of Life: FAQLQ-PF
time frame: At baseline, after 3.5 years
description: Quality Of Life, reported by questionnaire (FAQLQ-PF) after completion of the intervention (3.5 years) compared to pre-trial baseline level. The scale used is Emotional Impact, Food Related anxiety and Dietary Limitations. Each question of the FAQLQ is answered on a 7-point scale. Total FAQLQ scores and domain scores are calculated by dividing the sum of completed items by the number of completed items. Total FaQLQ and domain scores range from 1 "no impairment" to 7 "maximal impairment". Higher values are a worse outcome (low health related quality of life). Subscale is Health related quality of life (HRQoL summary score=(Emotional Impact subscale score + Food Related anxiety subscale score+Dietary Limitations subscale score)/3.
measure: Changes in nutritional status
time frame: At baseline, after 3.5 years
description: Body Mass Index (BMI) after completion of the intervention (3.5 years) compared to pre-trial baseline levels
measure: Frequency of treatment-demanding adverse effects
time frame: 3.5 years
description: Number of events with adrenaline injection within 2 hours after a dose of milk (one or two injections) during step-up and maintenance therapy respectively. Number of events with inhalation of bronchodilatator within 2 hours after a dose of milk during step up and maintenance therapy respectively. Number of participants with two or more events with adrenaline injections during step-up and maintenance respectively. Number of participants with two or more events with inhalation of bronchodilatator during step-up and maintenance therapy respectively. Number of participants with no events of adrenaline injections. Number of participants with no events of inhalation with bronchodilatator.
measure: Changes in level of IgE milk in blood
time frame: Baseline, 6 months, 3.5 years
description: Level of IgE milk including the components IgE casein, IgE lactoglobulin and lactalbumin at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins
measure: Changes in level of IgG4 milk in blood
time frame: Baseline, 6 months, 3.5 years
description: Level of IgG4 milk at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins
measure: Changes in level of IgA in saliva
time frame: Baseline, 6 months, 3.5 years
description: Level of IgA at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins
measure: Changes in overall microbial composition in stools
time frame: Baseline, 6 months, 3.5 years
description: The overall microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing
measure: Changes in overall microbial composition in saliva
time frame: Baseline, 6 months, 3.5 years
description: The microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing
arm group label: Active immunotherapy with milk protein
arm group type: Active Comparator
description: Daily dose fresh milk protein increased in 11 steps
arm group label: Control
arm group type: No Intervention
description: Diet free from milk protein
intervention type: Other
intervention name: Milk protein in fresh milk
description: Milk protein in increasing doses.
arm group label: Active immunotherapy with milk protein
criteria: 
gender: All
minimum age: 5 Years
maximum age: 15 Years
healthy volunteers: No
last name: Christina E West, MD,PhD
role: Principal Investigator
affiliation: Umeå University
last name: Christina West, Associated professor
phone: +46 703972792
email: christina.west@umu.se
last name: Solveig Röisgård
phone: +46 702791831
email: solveig.roisgard@regionjh.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Umeå University
investigator full name: Christina West
investigator title: Associate professor/Principal investigator
mesh term: Hypersensitivity
mesh term: Milk Hypersensitivity
mesh term: Caseins
sharing ipd: Undecided
ipd description: Undecided