<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/NCT03011632</url>
  </required_header>
  <id_info>
    <org_study_id>RNN/153/16/KE</org_study_id>
    <nct_id>NCT03011632</nct_id>
  </id_info>
  <brief_title>Response of the Airway in Sinusitis and Asthma</brief_title>
  <acronym>RAISe</acronym>
  <official_title>The Role of Nonspecific Immune Response of the Airway Mucosa in Children With Chronic Rhinosinusitis and Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Lodz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Lodz</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The project is intended to be realised in two phases. In the first stage, a case control&#xD;
      study will be performed. In the second phase, double-blind, placebo controlled study will be&#xD;
      conducted. In the first phase 3 groups of children will be compare: i) a group of children&#xD;
      suffering from chronic rhinosinusitis (CRS) (fulfilling the European Position Paper on&#xD;
      Rhinosinusitis and Nasal Polyps (EPOS) criteria) and asthma (fulfilling the Asthma Predictive&#xD;
      Index (API) criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS&#xD;
      (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria)&#xD;
      (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS&#xD;
      criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the&#xD;
      second phase the effect of intranasal glucocorticosteroids will be assessed. The following&#xD;
      research methods will be used: CRS-symptom score questionnaire (SN-5) and Childhood Asthma&#xD;
      Control Test (cACT) questionnaires, skin prick test, spirometry, measurement of nitric oxide&#xD;
      NO in exhaled breath (FeNO), taste perception test, eosinophil morphology assessment, ratio:&#xD;
      glucose concentration in nasal secretion/serum glucose level, concentration of specific&#xD;
      immunoglobulin (Ig) E, total immunoglobulin G (IgG) and immunoglobulin A (IgA), the&#xD;
      proportion of innate lymphoid cells (ILC) and regulatory lymphocytes cells in the peripheral&#xD;
      blood. Endoscopic examination of the upper airways will be performed and samples of the&#xD;
      mucosa will be taken. The mucosal examination will be as follows: i) polymerase chain&#xD;
      reaction (PCR) examination for the detection of the presence of viral and bacterial genetic&#xD;
      material, ii) measurement of the expression of the various messenger ribonucleic acid (mRNA),&#xD;
      iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT)&#xD;
      genes and iv) percentage of ILCs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Persistence of CRS and asthma require multiple interconnected feedback and feed-forward&#xD;
      circuits between ILCs and epithelial cells. It seems that type 2 ILCs (ILC2) are the most&#xD;
      important accelerators of type II immune response that prepare cytokine microenvironment for&#xD;
      Th2 cells chronic activation. What decide on ILC2 accumulation - this is an urgent question.&#xD;
      The aim of the proposed project is to examine the role of the innate immune response of&#xD;
      airways in children suffering from chronic rhinosinusitis and asthma.&#xD;
&#xD;
      The project is intended to be realised in two phases. In the first stage, a case control&#xD;
      study will be performed. In the second phase, double-blind, placebo controlled study will be&#xD;
      conducted. In the first phase 3 groups of children will be compare: i) a group of children&#xD;
      suffering from CRS (fulfilling the EPOS criteria) and asthma (fulfilling the API criteria)&#xD;
      (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS&#xD;
      criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a&#xD;
      group of children without symptoms of CRS (negative EPOS criteria) and without asthma&#xD;
      symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of&#xD;
      intranasal glucocorticosteroids will be assessed. The following research methods will be&#xD;
      used: SN-5 and cACT questionnaires, skin prick test, spirometry, measurement of NO in exhaled&#xD;
      breath, taste perception test, eosinophil morphology assessment, ratio: glucose concentration&#xD;
      in nasal secretion/serum glucose level, concentration of specific immunoglobulin E, total IgG&#xD;
      and IgA, the proportion of ILC2 cells and regulatory cells in the peripheral blood.&#xD;
      Endoscopic examination of the upper airways will be performed and samples of the mucosa will&#xD;
      be taken. The mucosal examination will be as follows: i) PCR examination for the detection of&#xD;
      the presence of viral and bacterial genetic material, ii) measurement of the expression of&#xD;
      the various mRNA types, iii) measurement of the expression of mRNA for the&#xD;
      Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILC 1, 2 and 3 cells and&#xD;
      regulatory cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">August 2019</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Asthma Control Test for children (cACT™)</measure>
    <time_frame>12 months</time_frame>
    <description>Childhood Asthma Control Test (cACT™), will be used, which has been recommended by the Global Initiative for Asthma (GINA) Report</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SN-5</measure>
    <time_frame>12 months</time_frame>
    <description>validated questionnaire for the assessment for quality of life in children with CRS (5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spirometry</measure>
    <time_frame>12 months</time_frame>
    <description>Respiratory function tests will be performed according to the American Thoracic Society (ATS) standards. The best result of three spirometric maneuvers will be selected for the analysis of obstructive disorders and the level of disease severity according to the standards of the Polish Society of Lung Diseases. The analysis will include FEV1% (A/N% - the percent of the measured to predicted value).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal fraction of exhaled nitric oxide (nFeNO) Measurements</measure>
    <time_frame>12 months</time_frame>
    <description>Measurements of nasal fraction of exhaled nitric oxide (nFeNO) will be performed using an electrochemical analyzer (ExpAir) according to the manufacturer's instructions. The detection limit ranged from 1 ppb to 6000 ppb.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose concentration</measure>
    <time_frame>12 months</time_frame>
    <description>Glucose concentration in serum and in nasal secretions will be assessed using glucose oxidase sticks (Roche, Lewes, East Sussex, U.K.). Nasal glucose concentration will analyzed in the context of blood glucose level using following ratio: nasal glucose level/blood glucose level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunophenotyping</measure>
    <time_frame>12 months</time_frame>
    <description>Mucosa - The nasal mucosa sample will be gently processed (mechanical dissociation, mild enzyme digestion) to produce a single cell suspension. It will be further fixed and stained with specific cocktail of fluorescent dye-stained antibody and then cell identification will be performed by flow cytometry. The relative count of all cell subsets will be determined. All procedures will be performed in buffers containing brefeldin and/or monesin to prevent dislocation of proteins of interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quantitative polymerase chain reaction (qPCR)</measure>
    <time_frame>12 months</time_frame>
    <description>Total RNA will be isolated from mucosa samples and then reverse-transcribed with e.g. Thermo Scientific Maxima Reverse Transcriptase. qPCR reaction will be performed using house-designed primer sets. Relative expression of genes of interest (involved in innate response) will be analyzed against selected house-keeping gene transcripts.&#xD;
Manufacturer recommended procedure will be used to quantify Human Epithelial to Mesenchymal Transition gene panel and Multiplex Real-Time PCR for pathogen genes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Sinusitis</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>mometasone nasal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo mometasone</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>a group of children without immunoglobulin E (IgE) - dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mometasone Nasal</intervention_name>
    <description>a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% Sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months</description>
    <arm_group_label>mometasone nasal</arm_group_label>
    <other_name>NasometinTM, Sandoz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo mometasone</intervention_name>
    <description>a group of children without IgE-dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,</description>
    <arm_group_label>placebo mometasone</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a group of children (n=90) suffering from CRS (fulfilling the EPOS criteria, European&#xD;
             Position Paper on Rhinosinusitis and Nasal Polyps) and asthma (fulfilling the API&#xD;
             criteria, Asthma Predictive Index), including a 30-person subgroup diagnosed with&#xD;
             clinically significant IgE-dependent hypersensitivity (accordance between symptoms and&#xD;
             current exposure to sensitizing allergen),&#xD;
&#xD;
          -  a group of children (n=30) suffering from CRS (fulfilling the EPOS criteria) but&#xD;
             without asthma symptoms (negative API criteria), including a 15-person subgroup&#xD;
             diagnosed with clinically significant IgE-dependent hypersensitivity (accordance&#xD;
             between symptoms and current exposure to sensitizing allergen),&#xD;
&#xD;
          -  a group of children (n=30) without symptoms of CRS (negative EPOS criteria) and&#xD;
             without asthma symptoms (negative API criteria).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  food allergy with symptoms affecting the respiratory tract&#xD;
&#xD;
          -  contraindication to nasal endoscopy or contraindication to nasal mucosa biopsy&#xD;
&#xD;
          -  hypertrophy of the third tonsil exceeding 60% of the nasopharynx (the criterion of&#xD;
             obstruction being an indication for adenoidectomy). In these patients, the anatomical&#xD;
             nasal obstruction may be the single cause of chronic inflammation in the airways, and&#xD;
             hence verification of the hypotheses is impossible&#xD;
&#xD;
          -  confirmed immunodeficiency&#xD;
&#xD;
          -  exacerbation of asthma requiring systemic administration of glucocorticosteroids&#xD;
&#xD;
          -  obesity, exposure to tobacco smoke&#xD;
&#xD;
          -  other chronic illnesses and clinical conditions, which in the opinion of the&#xD;
             researcher may influence the evaluation and the course of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>8 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pawel Majak, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital,</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland</name>
      <address>
        <city>Lodz</city>
        <zip>90-153</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>August 12, 2019</last_update_submitted>
  <last_update_submitted_qc>August 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Lodz</investigator_affiliation>
    <investigator_full_name>Pawel Majak</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mometasone Furoate</mesh_term>
  </intervention_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/NCT03011632
org study id: RNN/153/16/KE
nct id: NCT03011632
lead sponsor: 
has dmc: No
The project is intended to be realised in two phases. In the first stage, a case control
      study will be performed. In the second phase, double-blind, placebo controlled study will be
      conducted. In the first phase 3 groups of children will be compare: i) a group of children
      suffering from chronic rhinosinusitis (CRS) (fulfilling the European Position Paper on
      Rhinosinusitis and Nasal Polyps (EPOS) criteria) and asthma (fulfilling the Asthma Predictive
      Index (API) criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS
      (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria)
      (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS
      criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the
      second phase the effect of intranasal glucocorticosteroids will be assessed. The following
      research methods will be used: CRS-symptom score questionnaire (SN-5) and Childhood Asthma
      Control Test (cACT) questionnaires, skin prick test, spirometry, measurement of nitric oxide
      NO in exhaled breath (FeNO), taste perception test, eosinophil morphology assessment, ratio:
      glucose concentration in nasal secretion/serum glucose level, concentration of specific
      immunoglobulin (Ig) E, total immunoglobulin G (IgG) and immunoglobulin A (IgA), the
      proportion of innate lymphoid cells (ILC) and regulatory lymphocytes cells in the peripheral
      blood. Endoscopic examination of the upper airways will be performed and samples of the
      mucosa will be taken. The mucosal examination will be as follows: i) polymerase chain
      reaction (PCR) examination for the detection of the presence of viral and bacterial genetic
      material, ii) measurement of the expression of the various messenger ribonucleic acid (mRNA),
      iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT)
      genes and iv) percentage of ILCs.
Persistence of CRS and asthma require multiple interconnected feedback and feed-forward
      circuits between ILCs and epithelial cells. It seems that type 2 ILCs (ILC2) are the most
      important accelerators of type II immune response that prepare cytokine microenvironment for
      Th2 cells chronic activation. What decide on ILC2 accumulation - this is an urgent question.
      The aim of the proposed project is to examine the role of the innate immune response of
      airways in children suffering from chronic rhinosinusitis and asthma.

      The project is intended to be realised in two phases. In the first stage, a case control
      study will be performed. In the second phase, double-blind, placebo controlled study will be
      conducted. In the first phase 3 groups of children will be compare: i) a group of children
      suffering from CRS (fulfilling the EPOS criteria) and asthma (fulfilling the API criteria)
      (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS
      criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a
      group of children without symptoms of CRS (negative EPOS criteria) and without asthma
      symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of
      intranasal glucocorticosteroids will be assessed. The following research methods will be
      used: SN-5 and cACT questionnaires, skin prick test, spirometry, measurement of NO in exhaled
      breath, taste perception test, eosinophil morphology assessment, ratio: glucose concentration
      in nasal secretion/serum glucose level, concentration of specific immunoglobulin E, total IgG
      and IgA, the proportion of ILC2 cells and regulatory cells in the peripheral blood.
      Endoscopic examination of the upper airways will be performed and samples of the mucosa will
      be taken. The mucosal examination will be as follows: i) PCR examination for the detection of
      the presence of viral and bacterial genetic material, ii) measurement of the expression of
      the various mRNA types, iii) measurement of the expression of mRNA for the
      Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILC 1, 2 and 3 cells and
      regulatory cells.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Asthma Control Test for children (cACT™)
time frame: 12 months
description: Childhood Asthma Control Test (cACT™), will be used, which has been recommended by the Global Initiative for Asthma (GINA) Report
measure: SN-5
time frame: 12 months
description: validated questionnaire for the assessment for quality of life in children with CRS (5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations)
measure: Spirometry
time frame: 12 months
description: Respiratory function tests will be performed according to the American Thoracic Society (ATS) standards. The best result of three spirometric maneuvers will be selected for the analysis of obstructive disorders and the level of disease severity according to the standards of the Polish Society of Lung Diseases. The analysis will include FEV1% (A/N% - the percent of the measured to predicted value).
measure: Nasal fraction of exhaled nitric oxide (nFeNO) Measurements
time frame: 12 months
description: Measurements of nasal fraction of exhaled nitric oxide (nFeNO) will be performed using an electrochemical analyzer (ExpAir) according to the manufacturer's instructions. The detection limit ranged from 1 ppb to 6000 ppb.
measure: Glucose concentration
time frame: 12 months
description: Glucose concentration in serum and in nasal secretions will be assessed using glucose oxidase sticks (Roche, Lewes, East Sussex, U.K.). Nasal glucose concentration will analyzed in the context of blood glucose level using following ratio: nasal glucose level/blood glucose level.
measure: Immunophenotyping
time frame: 12 months
description: Mucosa - The nasal mucosa sample will be gently processed (mechanical dissociation, mild enzyme digestion) to produce a single cell suspension. It will be further fixed and stained with specific cocktail of fluorescent dye-stained antibody and then cell identification will be performed by flow cytometry. The relative count of all cell subsets will be determined. All procedures will be performed in buffers containing brefeldin and/or monesin to prevent dislocation of proteins of interest.
measure: quantitative polymerase chain reaction (qPCR)
time frame: 12 months
description: Total RNA will be isolated from mucosa samples and then reverse-transcribed with e.g. Thermo Scientific Maxima Reverse Transcriptase. qPCR reaction will be performed using house-designed primer sets. Relative expression of genes of interest (involved in innate response) will be analyzed against selected house-keeping gene transcripts.
Manufacturer recommended procedure will be used to quantify Human Epithelial to Mesenchymal Transition gene panel and Multiplex Real-Time PCR for pathogen genes
arm group label: mometasone nasal
arm group type: Experimental
description: a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months,
arm group label: placebo mometasone
arm group type: Placebo Comparator
description: a group of children without immunoglobulin E (IgE) - dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,
intervention type: Drug
intervention name: Mometasone Nasal
description: a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% Sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months
arm group label: mometasone nasal
other name: NasometinTM, Sandoz
intervention type: Drug
intervention name: placebo mometasone
description: a group of children without IgE-dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,
arm group label: placebo mometasone
other name: placebo
criteria: 
gender: All
minimum age: 4 Years
maximum age: 8 Years
healthy volunteers: No
last name: Pawel Majak, MD, PhD
role: Principal Investigator
affiliation: Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital,
facility: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Medical University of Lodz
investigator full name: Pawel Majak
investigator title: MD, PhD
mesh term: Sinusitis
mesh term: Asthma
mesh term: Mometasone Furoate
sharing ipd: No