<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/NCT03816800</url>
  </required_header>
  <id_info>
    <org_study_id>1370/2018</org_study_id>
    <nct_id>NCT03816800</nct_id>
  </id_info>
  <brief_title>Iron and Pollen Allergy in Women</brief_title>
  <official_title>Investigating the Association of Iron and Pollen Allergy in Female Subjects Studie Zur Wirkung Von Eisen Auf Pollenallergikerinnen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</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>
      Iron deficiency and anemia are clearly associated with the onset of allergy and allergic&#xD;
      diseases, whereas an improved iron status seems to prevent the onset of allergy in humans.&#xD;
      Iron-deficiency can be absolute or functional. Functional iron-deficiency occurs during&#xD;
      immune activation and may be reflective for the hyperactive state of atopic subjects.&#xD;
&#xD;
      The investigators plan a prophylactic dietary intervention study in atopic/allergic and&#xD;
      non-allergic individuals that transport chelated iron to immune cells. Over the course of six&#xD;
      months, oral supplementation of placebo or whey protein-bound chelated iron will be given and&#xD;
      1) clinical reactivity 2) iron status and 3) changes in the microflora due to the treatment&#xD;
      will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is no state-of-the-art prophylactic treatment for atopy. Once allergy develops,&#xD;
      allergens should be avoided, and specific allergen immunotherapy applied. The initial cause&#xD;
      of the onset of allergy, namely the immune hyperactive state of the atopic subjects, is not&#xD;
      addressed at all. The investigators hypothesize that atopy is defined by a mild functional&#xD;
      iron deficiency and that improving the iron status of immune cells will decrease the&#xD;
      reactivity of these cells.&#xD;
&#xD;
      In this prophylactic dietary intervention study oral supplementation of placebo or chelated&#xD;
      and whey protein-bound iron will be given over the course of six months to allergic and&#xD;
      non-allergic women. Changes in 1) the clinical reactivity 2) the iron status and 3) the&#xD;
      microflora will be assessed. The study will be the first systematic approach in humans to&#xD;
      assess the contribution of iron deficiency to allergy and will be pivotal in supporting the&#xD;
      implementation of prophylactic and therapeutic recommendations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2019</start_date>
  <completion_date type="Actual">October 29, 2020</completion_date>
  <primary_completion_date type="Actual">October 28, 2020</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>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Symptom severity - Total nasal symptom score</measure>
    <time_frame>Baseline</time_frame>
    <description>Symptoms (with max 2 points for secretions, irritations and distant symptoms): score of 6 means all symptoms present (secretion, irritations and distant symptoms)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Symptom severity - Total nasal symptom score</measure>
    <time_frame>8 months</time_frame>
    <description>Symptoms (with max 2 points for secretions, irritations and distant symptoms): score of 6 means all symptoms present (secretion, irritations and distant symptoms)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean daily combined symptom medication score during the peak of the pollen season</measure>
    <time_frame>up to 6 months</time_frame>
    <description>The score will be recorded daily for 45-180 days during the pollen season</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron status</measure>
    <time_frame>Baseline</time_frame>
    <description>Hemoglobin, Ferritin, hepcidin, hemopexin,ceruloplasmin, iron and soluble transferrin receptor concentrations, transferrin saturation in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron status</measure>
    <time_frame>8 months</time_frame>
    <description>Hemoglobin, Ferritin, hepcidin, hemopexin,ceruloplasmin, iron and soluble transferrin receptor concentrations, transferrin saturation in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory - Microbiome</measure>
    <time_frame>baseline</time_frame>
    <description>microbial composition will be assessed by 16S rRNA sequencing in order to determine bacterial communities present in samples, their relative abundance and overall diversity. Samples: gastrointestinal and nasal samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory - Microbiome</measure>
    <time_frame>8 months</time_frame>
    <description>microbial composition will be assessed by 16S rRNA sequencing in order to determine bacterial communities present in samples, their relative abundance and overall diversity. Samples: gastrointestinal and nasal samples</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Allergy Pollen</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Placebo-Allergic</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Over the course of 6 months allergic participants receive twice daily a placebo tablets.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active-Allergic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Over the course of 6 months allergic participants receive twice daily a dietary supplement containing whey protein-bound, chelated iron.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>ImmunoBon</intervention_name>
    <description>The dietary agent contains vitamin A, Zn, chelated iron and whey proteins.</description>
    <arm_group_label>Active-Allergic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>the dietary agent does not contain vitamin A, Zn, chelated iron and whey proteins</description>
    <arm_group_label>Placebo-Allergic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants will be healthy premenopausal women over 18 years of age. Allergic&#xD;
             participants should have been diagnosed with allergic rhinitis against birch and/or&#xD;
             grass pollen.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with co-morbidities such as diabetes mellitus, disorders of the liver&#xD;
             including hemochromatosis or kidney, autoimmune and metabolic diseases or malignancies&#xD;
             or who use medications (e.g. antibiotics, PPIs) that influence the iron, inflammatory&#xD;
             or microbial status will be excluded. Further exclusion criteria are pregnancy,&#xD;
             lactation, zinc, and iron supplementation and smoking. Subjects with a history of&#xD;
             major bleeding (including trauma, surgery, other major blood loss) within the last 2&#xD;
             years and blood transfusion within the last 2 years, or with a history of significant&#xD;
             breakthrough bleeding will be excluded. Volunteers will be asked to cease blood&#xD;
             donation at least three months before recruitment. Allergics with a history of an&#xD;
             allergen-induced anaphylactic shock or with severe, uncontrolled asthma who in the&#xD;
             last two years have received allergen immunotherapy or an anti-IgE therapy will be&#xD;
             excluded.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>premenopausal women</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franziska Roth-Walter, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The interuniversity Messerli Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>August 30, 2021</last_update_submitted>
  <last_update_submitted_qc>August 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Franziska Roth-Walter</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Allergy</keyword>
  <keyword>iron-deficiency</keyword>
  <keyword>birch</keyword>
  <keyword>grass</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhinitis, Allergic, Seasonal</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <!-- 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/NCT03816800
org study id: 1370/2018
nct id: NCT03816800
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Iron deficiency and anemia are clearly associated with the onset of allergy and allergic
      diseases, whereas an improved iron status seems to prevent the onset of allergy in humans.
      Iron-deficiency can be absolute or functional. Functional iron-deficiency occurs during
      immune activation and may be reflective for the hyperactive state of atopic subjects.

      The investigators plan a prophylactic dietary intervention study in atopic/allergic and
      non-allergic individuals that transport chelated iron to immune cells. Over the course of six
      months, oral supplementation of placebo or whey protein-bound chelated iron will be given and
      1) clinical reactivity 2) iron status and 3) changes in the microflora due to the treatment
      will be assessed.
There is no state-of-the-art prophylactic treatment for atopy. Once allergy develops,
      allergens should be avoided, and specific allergen immunotherapy applied. The initial cause
      of the onset of allergy, namely the immune hyperactive state of the atopic subjects, is not
      addressed at all. The investigators hypothesize that atopy is defined by a mild functional
      iron deficiency and that improving the iron status of immune cells will decrease the
      reactivity of these cells.

      In this prophylactic dietary intervention study oral supplementation of placebo or chelated
      and whey protein-bound iron will be given over the course of six months to allergic and
      non-allergic women. Changes in 1) the clinical reactivity 2) the iron status and 3) the
      microflora will be assessed. The study will be the first systematic approach in humans to
      assess the contribution of iron deficiency to allergy and will be pivotal in supporting the
      implementation of prophylactic and therapeutic recommendations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Symptom severity - Total nasal symptom score
time frame: Baseline
description: Symptoms (with max 2 points for secretions, irritations and distant symptoms): score of 6 means all symptoms present (secretion, irritations and distant symptoms)
measure: Symptom severity - Total nasal symptom score
time frame: 8 months
description: Symptoms (with max 2 points for secretions, irritations and distant symptoms): score of 6 means all symptoms present (secretion, irritations and distant symptoms)
measure: Mean daily combined symptom medication score during the peak of the pollen season
time frame: up to 6 months
description: The score will be recorded daily for 45-180 days during the pollen season
measure: Iron status
time frame: Baseline
description: Hemoglobin, Ferritin, hepcidin, hemopexin,ceruloplasmin, iron and soluble transferrin receptor concentrations, transferrin saturation in %
measure: Iron status
time frame: 8 months
description: Hemoglobin, Ferritin, hepcidin, hemopexin,ceruloplasmin, iron and soluble transferrin receptor concentrations, transferrin saturation in %
measure: Exploratory - Microbiome
time frame: baseline
description: microbial composition will be assessed by 16S rRNA sequencing in order to determine bacterial communities present in samples, their relative abundance and overall diversity. Samples: gastrointestinal and nasal samples
measure: Exploratory - Microbiome
time frame: 8 months
description: microbial composition will be assessed by 16S rRNA sequencing in order to determine bacterial communities present in samples, their relative abundance and overall diversity. Samples: gastrointestinal and nasal samples
arm group label: Placebo-Allergic
arm group type: Placebo Comparator
description: Over the course of 6 months allergic participants receive twice daily a placebo tablets.
arm group label: Active-Allergic
arm group type: Active Comparator
description: Over the course of 6 months allergic participants receive twice daily a dietary supplement containing whey protein-bound, chelated iron.
intervention type: Dietary Supplement
intervention name: ImmunoBon
description: The dietary agent contains vitamin A, Zn, chelated iron and whey proteins.
arm group label: Active-Allergic
intervention type: Dietary Supplement
intervention name: Placebo
description: the dietary agent does not contain vitamin A, Zn, chelated iron and whey proteins
arm group label: Placebo-Allergic
criteria: 
gender: Female
gender based: Yes
gender description: premenopausal women
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Franziska Roth-Walter, PhD
role: Principal Investigator
affiliation: The interuniversity Messerli Research Institute
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Franziska Roth-Walter
investigator title: Principal Investigator
mesh term: Rhinitis, Allergic, Seasonal
mesh term: Hypersensitivity