<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/NCT03799328</url>
  </required_header>
  <id_info>
    <org_study_id>1000060633</org_study_id>
    <nct_id>NCT03799328</nct_id>
  </id_info>
  <brief_title>Low Dose Multi-OIT for Food Allergy (LoMo)</brief_title>
  <acronym>LoMO</acronym>
  <official_title>Low Dose Multi Allergen Oral Immunotherapy for Food Allergy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</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>
      Oral immunotherapy (OIT) is a food allergy treatment where small amounts of the food a child&#xD;
      is allergic to is eaten and gradually increased over time with the aim to be able to eat a&#xD;
      certain amount of the allergen without experiencing an allergic reaction. While this process&#xD;
      works in many children there are concerns about safety, feasibility and drop-outs and how to&#xD;
      adapt protocols for multiple allergies.&#xD;
&#xD;
      Many OIT trials have targeted approximately 4000mg of single food/day. In these trials up to&#xD;
      40% drop-out. There is evidence much lower doses can have beneficial effects.&#xD;
&#xD;
      The investigators will evaluate if low doses of foods can allow for OIT to multiple foods.&#xD;
      This approach may have efficacy against accidental exposure and be able to demonstrate immune&#xD;
      changes. This approach may have a low burden of treatment and a low rate of allergic&#xD;
      reactions and&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm, open label, study of the intervention of low dose multiple-nut OIT in&#xD;
      nut allergic children.&#xD;
&#xD;
      After meeting eligibility criteria, participants will have a food challenge to 2-5 nuts.&#xD;
&#xD;
      If the oral food challenge is positive, participants will be enrolled in the study to&#xD;
      multiple nut OIT. A blood draw and quality of life (QOL) survey will occur at baseline.&#xD;
&#xD;
      Participants will have dose escalation visits of the multiple nut OIT every 2 months to a&#xD;
      target dose of 30mg of each nut protein. A blood draw and QOL survey will occur at 6 months.&#xD;
&#xD;
      Participants will then continue with daily ingestion of the 30mg of each nut protein for 1&#xD;
      year with visits every 3 months.&#xD;
&#xD;
      After 18 months from the start of the study, another oral food challenge will be given to&#xD;
      participants to assess the change in the maximum tolerated dose of nuts. A blood draw will&#xD;
      assess changes in the immune parameters. A QOL survey will occur at 18 months to assess&#xD;
      changes in QOL.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 23, 2019</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Desensitization to allergic food as assessed by change in maximum tolerated dose in a dichotomous manner</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Change in how much nuts the participant can eat without an allergic reaction after the low dose OIT assessed as dichotomous did the participant reach 5 times the baseline eliciting dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunological change in IgG4</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Change in allergen specific immunoglobulin G4 (IgG4) from baseline to end</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Desensitization to allergic food as assessed by change in maximum tolerated dose on a linear scale</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>A continuous variable amount tolerated at baseline vs at end</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological change in IgG4</measure>
    <time_frame>pre-study, month 18</time_frame>
    <description>Change in IgG4 from measures from historical data to 18 month of study. Some patients will have historical IgG4 values to compare</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Desensitization to allergic food as assessed by maximum tolerated dose</measure>
    <time_frame>month 18</time_frame>
    <description>Did they reach 300mg (cumulative) on the 18 month exit oral food challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Desensitization to allergic food as assessed by maximum tolerated dose</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Did they reach 140mg (cumulative) on the 18 month exit oral food challenge</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility analysis as assessed by can the patients achieve the maintenance dosing of the allergen mix for OIT</measure>
    <time_frame>month 18</time_frame>
    <description>Proportion who achieve maintenance doses of their allergen mix (descriptive)</description>
  </other_outcome>
  <other_outcome>
    <measure>Feasibility analysis as assessed by drop-out rate</measure>
    <time_frame>month 18</time_frame>
    <description>Proportion who drop-out of the study (descriptive)</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events: Safety analysis as assessed by use of epinephrine</measure>
    <time_frame>month 18</time_frame>
    <description>Administration of epinephrine; (descriptive);</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of life scale</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Change in quality of life at 18m of children compared to baseline assessment (using validated questionnaire: Food allergy quality of life questionnaires (FAQLQ) FAQLQ Parental form (PF) for ages 0-12 OR the FAQLQ-teenager form (TF) using total score. The FAQLQ total and domain scores range from 1-7 with higher scores indicative of worse health related quality of life with the total score being the average of the domain scores. The domains include Emotional Impact, Social and Dietary Restrictions, Food Anxiety, Allergen Avoidance, and Risk of Accidental Exposure.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in allergen specific IgE, and components</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Change in allergen specific IgE, and components via microarray</description>
  </other_outcome>
  <other_outcome>
    <measure>Basophil activation test</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Basophil activation test</description>
  </other_outcome>
  <other_outcome>
    <measure>Skin prick test (SPT) reactivity to the individual nut extracts</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>The size of the skin prick test will be compared</description>
  </other_outcome>
  <other_outcome>
    <measure>High content functional immune profiling via mass cytometry and single cell sorting</measure>
    <time_frame>pre-study, month 18</time_frame>
    <description>Compare the change in the immune pattern</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with treatment related adverse effects</measure>
    <time_frame>month 0, month 18</time_frame>
    <description>Diaries will be analyzed for allergic symptoms and tabulated</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Food Allergy</condition>
  <arm_group>
    <arm_group_label>multi-OIT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose OIT with multiple allergens</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>multi-OIT</intervention_name>
    <description>low dose OIT to multiple foods</description>
    <arm_group_label>multi-OIT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relevant allergy to 2-5 nuts&#xD;
&#xD;
          -  Serum immunoglobulin E (IgE) &gt;0.35 kilounits/L (kU/L) (determined by UniCAP within the&#xD;
             past 12 months) and/or a SPT to nut &gt;3 mm compared to control&#xD;
&#xD;
          -  Positive oral food challenge (OFC) to less than 300mg of a nut in the nut mix at&#xD;
             baseline (cumulative 444mg).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of frequent or repeated, severe or life-threatening episodes of anaphylactic&#xD;
             shock&#xD;
&#xD;
          -  use of omalizumab or other non-traditional forms of allergen immunomodulatory therapy&#xD;
             (not including corticosteroids) or biologic therapy in the 12 months prior to study&#xD;
             entry&#xD;
&#xD;
          -  history of eosinophilic gastrointestinal disease, uncontrolled asthma as defined by&#xD;
             Global Initiative for Asthma (GINA)&#xD;
&#xD;
          -  use of beta-blockers(oral)&#xD;
&#xD;
          -  use of angiotensin-converting enzyme inhibitors (ACE)&#xD;
&#xD;
          -  fails to tolerate 4mg of peanut after the first desensitization day&#xD;
&#xD;
          -  Other significant medical conditions that in the opinion of the investigator prevent&#xD;
             participation in the study,&#xD;
&#xD;
          -  Previous intubation due to allergies or asthma,&#xD;
&#xD;
          -  Symptomatic atopic dermatitis or chronic urticaria which may interfere with ability to&#xD;
             evaluate oral immunotherapy and /or requiring daily medication including&#xD;
             antihistamines,&#xD;
&#xD;
          -  Patients with problems related to compliance or following study instructions,&#xD;
             Inability to come to hospital every for dose escalation&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Non-fluency in English because participants may need to communicate with us after&#xD;
             hours and be able to describe symptoms and concerns and follow instructions to treat&#xD;
             anaphylaxis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julia Upton</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital for Sick Children</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>May 4, 2022</last_update_submitted>
  <last_update_submitted_qc>May 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Julia Upton</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Food Hypersensitivity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03799328/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03799328
org study id: 1000060633
nct id: NCT03799328
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Oral immunotherapy (OIT) is a food allergy treatment where small amounts of the food a child
      is allergic to is eaten and gradually increased over time with the aim to be able to eat a
      certain amount of the allergen without experiencing an allergic reaction. While this process
      works in many children there are concerns about safety, feasibility and drop-outs and how to
      adapt protocols for multiple allergies.

      Many OIT trials have targeted approximately 4000mg of single food/day. In these trials up to
      40% drop-out. There is evidence much lower doses can have beneficial effects.

      The investigators will evaluate if low doses of foods can allow for OIT to multiple foods.
      This approach may have efficacy against accidental exposure and be able to demonstrate immune
      changes. This approach may have a low burden of treatment and a low rate of allergic
      reactions and
This is a single-arm, open label, study of the intervention of low dose multiple-nut OIT in
      nut allergic children.

      After meeting eligibility criteria, participants will have a food challenge to 2-5 nuts.

      If the oral food challenge is positive, participants will be enrolled in the study to
      multiple nut OIT. A blood draw and quality of life (QOL) survey will occur at baseline.

      Participants will have dose escalation visits of the multiple nut OIT every 2 months to a
      target dose of 30mg of each nut protein. A blood draw and QOL survey will occur at 6 months.

      Participants will then continue with daily ingestion of the 30mg of each nut protein for 1
      year with visits every 3 months.

      After 18 months from the start of the study, another oral food challenge will be given to
      participants to assess the change in the maximum tolerated dose of nuts. A blood draw will
      assess changes in the immune parameters. A QOL survey will occur at 18 months to assess
      changes in QOL.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Desensitization to allergic food as assessed by change in maximum tolerated dose in a dichotomous manner
time frame: month 0, month 18
description: Change in how much nuts the participant can eat without an allergic reaction after the low dose OIT assessed as dichotomous did the participant reach 5 times the baseline eliciting dose
measure: Immunological change in IgG4
time frame: month 0, month 18
description: Change in allergen specific immunoglobulin G4 (IgG4) from baseline to end
measure: Desensitization to allergic food as assessed by change in maximum tolerated dose on a linear scale
time frame: month 0, month 18
description: A continuous variable amount tolerated at baseline vs at end
measure: Immunological change in IgG4
time frame: pre-study, month 18
description: Change in IgG4 from measures from historical data to 18 month of study. Some patients will have historical IgG4 values to compare
measure: Desensitization to allergic food as assessed by maximum tolerated dose
time frame: month 18
description: Did they reach 300mg (cumulative) on the 18 month exit oral food challenge
measure: Desensitization to allergic food as assessed by maximum tolerated dose
time frame: month 0, month 18
description: Did they reach 140mg (cumulative) on the 18 month exit oral food challenge
measure: Feasibility analysis as assessed by can the patients achieve the maintenance dosing of the allergen mix for OIT
time frame: month 18
description: Proportion who achieve maintenance doses of their allergen mix (descriptive)
measure: Feasibility analysis as assessed by drop-out rate
time frame: month 18
description: Proportion who drop-out of the study (descriptive)
measure: Incidence of Treatment-Emergent Adverse Events: Safety analysis as assessed by use of epinephrine
time frame: month 18
description: Administration of epinephrine; (descriptive);
measure: Quality of life scale
time frame: month 0, month 18
description: Change in quality of life at 18m of children compared to baseline assessment (using validated questionnaire: Food allergy quality of life questionnaires (FAQLQ) FAQLQ Parental form (PF) for ages 0-12 OR the FAQLQ-teenager form (TF) using total score. The FAQLQ total and domain scores range from 1-7 with higher scores indicative of worse health related quality of life with the total score being the average of the domain scores. The domains include Emotional Impact, Social and Dietary Restrictions, Food Anxiety, Allergen Avoidance, and Risk of Accidental Exposure.
measure: Change in allergen specific IgE, and components
time frame: month 0, month 18
description: Change in allergen specific IgE, and components via microarray
measure: Basophil activation test
time frame: month 0, month 18
description: Basophil activation test
measure: Skin prick test (SPT) reactivity to the individual nut extracts
time frame: month 0, month 18
description: The size of the skin prick test will be compared
measure: High content functional immune profiling via mass cytometry and single cell sorting
time frame: pre-study, month 18
description: Compare the change in the immune pattern
measure: Number of participants with treatment related adverse effects
time frame: month 0, month 18
description: Diaries will be analyzed for allergic symptoms and tabulated
arm group label: multi-OIT
arm group type: Experimental
description: Low dose OIT with multiple allergens
intervention type: Other
intervention name: multi-OIT
description: low dose OIT to multiple foods
arm group label: multi-OIT
criteria: 
gender: All
minimum age: 6 Months
maximum age: 15 Years
healthy volunteers: No
last name: Julia Upton
role: Principal Investigator
affiliation: The Hospital for Sick Children
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Julia Upton
investigator title: Principal Investigator
mesh term: Hypersensitivity
mesh term: Food Hypersensitivity
sharing ipd: No
provided document: 