<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/NCT04438525</url>
  </required_header>
  <id_info>
    <org_study_id>30-381 ex 17/18 (BATIRS)</org_study_id>
    <nct_id>NCT04438525</nct_id>
  </id_info>
  <brief_title>Is the BAT Inhibition Able to Replace Sting Challenges? (BATIRS)</brief_title>
  <official_title>Is the BAT Inhibition Able to Replace Sting Challenges?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Insect venom allergy is the major cause for severe allergic reactions in Europe. Wasps and&#xD;
      honeybees are responsible for the majority of these allergic reactions. Symptoms range from&#xD;
      generalized skin symptoms (wheals, swellings) to respiratory or cardiovascular problems such&#xD;
      as asthma, dizziness, loss of consciousness, or cardiac arrest. The regular administration of&#xD;
      insect venom ('venom immunotherapy') over up to 5 years is a well-established therapy,&#xD;
      providing long-term protection from further systemic sting reactions in the majority of&#xD;
      patients. However, there is no laboratory test which is able to identify patients who will&#xD;
      still react to an insect sting. The only reliable method available is stinging patients with&#xD;
      living insects ('sting challenges'). The key issue is that only few centers in Europe perform&#xD;
      sting challenges and many patients have no access to these tests. Therefore, it is of utmost&#xD;
      importance to find a method which is able to identify patients who are still at risk for&#xD;
      future allergic sting reactions.&#xD;
&#xD;
      The inhibition of the basophil activation test (BAT) could be a potential method to monitor&#xD;
      the effectiveness of immunotherapy. Basophils are cells which are activated in acute allergic&#xD;
      reactions. The basophil activation of blood donors with vespid venom allergy can be measured&#xD;
      after adding sera from allergic patients undergoing immunotherapy. In a preliminary study we&#xD;
      found that the activation of basophils could be inhibited in all patients treated with vespid&#xD;
      venom, however, results must be confirmed in a larger study.&#xD;
&#xD;
      In this study, a total of 219 patients with vespid venom allergy will be included. Those&#xD;
      patients who are receiving or who have already finished venom immunotherapy will be sting&#xD;
      challenged and blood samples will be taken to perform BAT inhibition experiments. At the same&#xD;
      time, donors with confirmed vespid venom allergy, who have not undergone immunotherapy, will&#xD;
      be recruited for a blood donation, which is necessary for the BAT inhibition tests.&#xD;
&#xD;
      If results of the preliminary study could be confirmed, the BAT inhibition will facilitate&#xD;
      monitoring the effectiveness of venom immunotherapy and patients would benefit from an early&#xD;
      detection of lacking tolerance and consequently from the increased venom dose preventing&#xD;
      future life threatening systemic sting reactions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 7, 2021</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">September 2026</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Outcome sting challenge vs. BAT Inhibition test</measure>
    <time_frame>4 hours</time_frame>
    <description>The primary endpoint for the study is the inhibition of the CD63 basophil response (BAT inhibition at a concentration of 11ng/ml) in vespid venom allergic patients. A minimum activation of 25% is required to see sufficient inhibition of basophil activity. Immunotherapy will be considered successful if the BAT inhibition (with added serum) is reduced by at least 80% compared to 'no serum'.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">219</enrollment>
  <condition>Vespid Venom Allergy</condition>
  <arm_group>
    <arm_group_label>early maintenance phase</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients who reached the maintenance dose of venom immunotherapy one week (max. +3 weeks) before recruitment will be sting challenged</description>
  </arm_group>
  <arm_group>
    <arm_group_label>maintenance phase</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients who reached the maintenance dose of venom immunotherapy one year (+/- 2 months) before recruitment will be sting challenged</description>
  </arm_group>
  <arm_group>
    <arm_group_label>after stopping VIT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients who finished venom immunotherapy two years (+/- 6 months) before recruitment (duration of VIT: at least 3 years) will be sting challenged</description>
  </arm_group>
  <arm_group>
    <arm_group_label>blood donors</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patients with confirmed vespid venom allergy who have not undergone venom immunotherapy (blood donation necessary to perform BAT Inhibition test)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>sting challenge</intervention_name>
    <description>At the Moment, sting challenges are the only reliable method to identify patients who are not protected by insect venom immunotherapy.</description>
    <arm_group_label>after stopping VIT</arm_group_label>
    <arm_group_label>early maintenance phase</arm_group_label>
    <arm_group_label>maintenance phase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood donation</intervention_name>
    <description>To perform BAT Inhibition Tests, blood samples of patients with confirmed vespid venom allergy, who have not undergone venom immunotherapy, are necessary.</description>
    <arm_group_label>blood donors</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Legally competent male and female subjects who are currently treated or who have been&#xD;
             treated with vespid venom immunotherapy&#xD;
&#xD;
          -  Age ≥18 and ≤70 years&#xD;
&#xD;
          -  Written consent of the participant after being informed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Uncontrolled cardiovascular disease&#xD;
&#xD;
          -  Uncontrolled asthma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Gunter J Sturm, MD, PhD</last_name>
    <phone>+4331638580318</phone>
    <email>gunter.sturm@medunigraz.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lisa Arzt-Gradwohl, PhD</last_name>
    <phone>+4331638578039</phone>
    <email>lisa.arzt@medunigraz.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Dermatology and Venerology, Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gunter J Sturm, MD, PhD</last_name>
      <phone>+4331638580318</phone>
      <email>gunter.sturm@medunigraz.at</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>July 14, 2023</last_update_submitted>
  <last_update_submitted_qc>July 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venom Hypersensitivity</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/NCT04438525
org study id: 30-381 ex 17/18 (BATIRS)
nct id: NCT04438525
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Insect venom allergy is the major cause for severe allergic reactions in Europe. Wasps and
      honeybees are responsible for the majority of these allergic reactions. Symptoms range from
      generalized skin symptoms (wheals, swellings) to respiratory or cardiovascular problems such
      as asthma, dizziness, loss of consciousness, or cardiac arrest. The regular administration of
      insect venom ('venom immunotherapy') over up to 5 years is a well-established therapy,
      providing long-term protection from further systemic sting reactions in the majority of
      patients. However, there is no laboratory test which is able to identify patients who will
      still react to an insect sting. The only reliable method available is stinging patients with
      living insects ('sting challenges'). The key issue is that only few centers in Europe perform
      sting challenges and many patients have no access to these tests. Therefore, it is of utmost
      importance to find a method which is able to identify patients who are still at risk for
      future allergic sting reactions.

      The inhibition of the basophil activation test (BAT) could be a potential method to monitor
      the effectiveness of immunotherapy. Basophils are cells which are activated in acute allergic
      reactions. The basophil activation of blood donors with vespid venom allergy can be measured
      after adding sera from allergic patients undergoing immunotherapy. In a preliminary study we
      found that the activation of basophils could be inhibited in all patients treated with vespid
      venom, however, results must be confirmed in a larger study.

      In this study, a total of 219 patients with vespid venom allergy will be included. Those
      patients who are receiving or who have already finished venom immunotherapy will be sting
      challenged and blood samples will be taken to perform BAT inhibition experiments. At the same
      time, donors with confirmed vespid venom allergy, who have not undergone immunotherapy, will
      be recruited for a blood donation, which is necessary for the BAT inhibition tests.

      If results of the preliminary study could be confirmed, the BAT inhibition will facilitate
      monitoring the effectiveness of venom immunotherapy and patients would benefit from an early
      detection of lacking tolerance and consequently from the increased venom dose preventing
      future life threatening systemic sting reactions.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Outcome sting challenge vs. BAT Inhibition test
time frame: 4 hours
description: The primary endpoint for the study is the inhibition of the CD63 basophil response (BAT inhibition at a concentration of 11ng/ml) in vespid venom allergic patients. A minimum activation of 25% is required to see sufficient inhibition of basophil activity. Immunotherapy will be considered successful if the BAT inhibition (with added serum) is reduced by at least 80% compared to 'no serum'.
arm group label: early maintenance phase
arm group type: Active Comparator
description: patients who reached the maintenance dose of venom immunotherapy one week (max. +3 weeks) before recruitment will be sting challenged
arm group label: maintenance phase
arm group type: Active Comparator
description: patients who reached the maintenance dose of venom immunotherapy one year (+/- 2 months) before recruitment will be sting challenged
arm group label: after stopping VIT
arm group type: Active Comparator
description: patients who finished venom immunotherapy two years (+/- 6 months) before recruitment (duration of VIT: at least 3 years) will be sting challenged
arm group label: blood donors
arm group type: Other
description: patients with confirmed vespid venom allergy who have not undergone venom immunotherapy (blood donation necessary to perform BAT Inhibition test)
intervention type: Diagnostic Test
intervention name: sting challenge
description: At the Moment, sting challenges are the only reliable method to identify patients who are not protected by insect venom immunotherapy.
arm group label: after stopping VIT
arm group label: early maintenance phase
arm group label: maintenance phase
intervention type: Other
intervention name: blood donation
description: To perform BAT Inhibition Tests, blood samples of patients with confirmed vespid venom allergy, who have not undergone venom immunotherapy, are necessary.
arm group label: blood donors
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gunter J Sturm, MD, PhD
phone: +4331638580318
email: gunter.sturm@medunigraz.at
last name: Lisa Arzt-Gradwohl, PhD
phone: +4331638578039
email: lisa.arzt@medunigraz.at
facility: 
status: Recruiting
contact: 
country: Austria
responsible party type: Sponsor
mesh term: Venom Hypersensitivity
sharing ipd: No