xml: <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/NCT06034145</url>
    </required_header>
    <id_info>
      <org_study_id>Lungeklinikken_Elsinore</org_study_id>
      <nct_id>NCT06034145</nct_id>
    </id_info>
    <brief_title>Methacholine Challenge Testing: Comparison of FEV1 and IOS Parameters in Adult Asthma Patients</brief_title>
    <official_title>Methacholine Challenge Testing: Comparison of FEV1 and IOS Parameters in Adult Asthma Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Allergi- og Lungeklinikken, Elsinore</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Allergi- og Lungeklinikken, Elsinore</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>
        A classic methacholine challenge test is considered positive when forced expiratory volumen&#xD;
        after one second (FEV1) decrease 20%. Impulse oscillometry (IOS) measures airway resistance&#xD;
        and reactance, and seems more sensitive to changes in small airways. In adult asthma&#xD;
        patients, we compare methacholine challenge test using both FEV1 and IOS.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Asthma is a common chronic disease that is characterized by a history of variable respiratory&#xD;
        symptoms and variable expiratory airflow limitation, and usually associated with airway&#xD;
        hyperresponsiveness (GINA).&#xD;
  &#xD;
        In general, FEV1 is used to test for airway hyperresponsiveness (AHR), and a 20% decrease&#xD;
        after methacholine challenge is considered a positive test (Coates 2017; ERJ).&#xD;
  &#xD;
        There is increasing recognition that the small airways are involved in 40-80% of patients&#xD;
        with asthma, and the function of these airways is overlooked (the &quot;silent zone&quot;) when&#xD;
        measuring FEV1, which mainly reflects the function of the central airways (Cottini M, J&#xD;
        Allergy Clin Immunol Pract 2019; Cottini M, 2022; Postma 2019 Lancet Respir Med).&#xD;
  &#xD;
        Small airway dysfunction (SAD) can be assessed by IOS where pressure applied to the airways&#xD;
        at a range of frequencies, and components of respiratory resistance and reactance are&#xD;
        measured. Resistance at 5 Hz (R5) and 20 Hz (R20), respectively, represent total airway&#xD;
        resistance and proximal airway resistance. The difference between these two values can be&#xD;
        calculated (R5-R20). High R5-R20 and low reactance at 5 Hz (X5) indicate the presence of SAD.&#xD;
  &#xD;
        A recent study showed that patients with a negative methacholine test measured by FEV1 may&#xD;
        report asthma-like symptoms and may have a positive test when measured by IOS (Urbankowski;&#xD;
        2021). The question is whether these patients are a subgroup of patients with SAD (based on&#xD;
        IOS at baseline) or are characterized in another way.&#xD;
  &#xD;
        Knowledge on the proportion of patients with AHR only measured by IOS (not by FEV1) and the&#xD;
        characteristics of these patients are sparse.&#xD;
  &#xD;
        Hypothesis &amp; Aims The aim of the present study was to determine the proportion of AHR to&#xD;
        methacholine measured by FEV1 and IOS, respectively, in patients with diagnosed asthma and to&#xD;
        compare patient characteristics and asthma medication in these four groups of patients: 1)&#xD;
        negative by FEV1 and IOS; 2) negative by FEV1 but positive by IOS; 3) positive by FEV1 but&#xD;
        negative by IOS; 4) positive by both tests.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>ACQ-6</measure>
      <time_frame>At entry (Cross sectional)</time_frame>
      <description>Asthma Control Questionnaire (ACQ6) will be used in the 6 sub-score version omitting FEV1 % of predicted</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Impulse Oscillometry</measure>
      <time_frame>At entry</time_frame>
      <description>Resistance at 5Hz (R5), R5-R20, reactance at 5Hz (X5), frequency response (Fres), areal under reactance curve (AX)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demographic data</measure>
      <time_frame>At entry</time_frame>
      <description>General demographic data, including age, sex (male/female), body mass index (BMI) (kg/m2), and smoking history will be recorded.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarker</measure>
      <time_frame>At entry</time_frame>
      <description>Serum eosinophils and hemoglobin will be measured</description>
    </primary_outcome>
    <primary_outcome>
      <measure>FeNO</measure>
      <time_frame>At entry</time_frame>
      <description>Measurement of Exhaled Nitric Oxide by NOBreath</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Lung function and body box</measure>
      <time_frame>At entry</time_frame>
      <description>Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the percentage of FEV1 in the estimated value will be measured at baseline and after methacholine test by Vyntus, Vyaire Medical. Body plethysmography with residual volumen (RV), total lung capacity (TLC), diffusion capacity of the lungs for carbon monoxide (DLCO), will be measured before methacholine test by Medical Electronic Construction (MEC).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Asthma medication</measure>
      <time_frame>At entry</time_frame>
      <description>Inhaled corticosteroids (ICS), long-acting beta2agonists (LABA), long-acting muscarinic antagonists (LAMA), Leukotriene antagonist, theophylline, and prednisolone - type and dose</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">500</enrollment>
    <condition>Bronchial Hyperreactivity</condition>
    <arm_group>
      <arm_group_label>Asthma</arm_group_label>
      <description>Asthma according to Gina Guidelines</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>No intervention</intervention_name>
      <description>No intervention</description>
      <arm_group_label>Asthma</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          This is a cross-sectional analysis of a single-centered, observational study on adult (≥18&#xD;
          years old) patients referred with known asthma or asthma-like symptoms to a lung specialist&#xD;
          clinic&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Doctor diagnosed asthma (based on symptoms and at least one positive asthma test&#xD;
               within the last 5 years (AHR; reversibility to beta2-agonist, ICS, prednisolone; peak&#xD;
               flow variation).&#xD;
  &#xD;
            -  Written informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  patients aged less than 18 years old.&#xD;
  &#xD;
            -  patients with an exacerbation or lower airway infection within 1 months.&#xD;
  &#xD;
            -  Pulmonary function test: FEV1 (% pred.) &lt; 60%&#xD;
  &#xD;
            -  Not able to perform spirometry or body plethysmography.&#xD;
  &#xD;
            -  Cognitive disorders and not able to answer ACQ.&#xD;
  &#xD;
            -  Treated with biologics.&#xD;
  &#xD;
            -  Pregnancy or breastfeeding&#xD;
  &#xD;
            -  Short-acting beta-agonists 6 h, long-acting beta-agonists 2 days, short-acting&#xD;
               anti-muscarinic agent 12 h, Long-acting anti-muscarinic agents 7 days, and Montelukast&#xD;
               3 days before methacholine challenge test (MCT).&#xD;
  &#xD;
            -  Comorbidity with significant influence on lung function and pulmonary symptoms eg.&#xD;
               COPD, bronchiectasis, ischemic heart disease, heart failure, atrial fibrillation,&#xD;
               uncontrolled hypertension (&gt;160/100 mmHg), lung cancer, lung resection, BMI&gt;40 kg/m2.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Thomas Ringbæk, MSci</last_name>
      <role>Principal Investigator</role>
      <affiliation>Allergy and Lung Clinic Elsinore</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Thomas Ringbæk, MSci</last_name>
      <phone>004521969087</phone>
      <email>thomasringbaek@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lars Frølund, MSci</last_name>
      <phone>004521777696</phone>
      <email>lars.froelund@dadlnet.dk</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Allergi- og Lungeklinikken, Elsinore</investigator_affiliation>
      <investigator_full_name>Thomas Ringbæk</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>asthma</keyword>
    <keyword>oscillometry</keyword>
    <keyword>spirometry</keyword>
    <keyword>bronchial hyperreactivity</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bronchial Hyperreactivity</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Publication in per-reviewed papers;</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06034145
  org study id: Lungeklinikken_Elsinore
  nct id: NCT06034145
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  A classic methacholine challenge test is considered positive when forced expiratory volumen
        after one second (FEV1) decrease 20%. Impulse oscillometry (IOS) measures airway resistance
        and reactance, and seems more sensitive to changes in small airways. In adult asthma
        patients, we compare methacholine challenge test using both FEV1 and IOS.
  Asthma is a common chronic disease that is characterized by a history of variable respiratory
        symptoms and variable expiratory airflow limitation, and usually associated with airway
        hyperresponsiveness (GINA).
  
        In general, FEV1 is used to test for airway hyperresponsiveness (AHR), and a 20% decrease
        after methacholine challenge is considered a positive test (Coates 2017; ERJ).
  
        There is increasing recognition that the small airways are involved in 40-80% of patients
        with asthma, and the function of these airways is overlooked (the "silent zone") when
        measuring FEV1, which mainly reflects the function of the central airways (Cottini M, J
        Allergy Clin Immunol Pract 2019; Cottini M, 2022; Postma 2019 Lancet Respir Med).
  
        Small airway dysfunction (SAD) can be assessed by IOS where pressure applied to the airways
        at a range of frequencies, and components of respiratory resistance and reactance are
        measured. Resistance at 5 Hz (R5) and 20 Hz (R20), respectively, represent total airway
        resistance and proximal airway resistance. The difference between these two values can be
        calculated (R5-R20). High R5-R20 and low reactance at 5 Hz (X5) indicate the presence of SAD.
  
        A recent study showed that patients with a negative methacholine test measured by FEV1 may
        report asthma-like symptoms and may have a positive test when measured by IOS (Urbankowski;
        2021). The question is whether these patients are a subgroup of patients with SAD (based on
        IOS at baseline) or are characterized in another way.
  
        Knowledge on the proportion of patients with AHR only measured by IOS (not by FEV1) and the
        characteristics of these patients are sparse.
  
        Hypothesis & Aims The aim of the present study was to determine the proportion of AHR to
        methacholine measured by FEV1 and IOS, respectively, in patients with diagnosed asthma and to
        compare patient characteristics and asthma medication in these four groups of patients: 1)
        negative by FEV1 and IOS; 2) negative by FEV1 but positive by IOS; 3) positive by FEV1 but
        negative by IOS; 4) positive by both tests.
  observational model: Case-Only
  time perspective: Prospective
  measure: ACQ-6
  time frame: At entry (Cross sectional)
  description: Asthma Control Questionnaire (ACQ6) will be used in the 6 sub-score version omitting FEV1 % of predicted
  measure: Impulse Oscillometry
  time frame: At entry
  description: Resistance at 5Hz (R5), R5-R20, reactance at 5Hz (X5), frequency response (Fres), areal under reactance curve (AX)
  measure: Demographic data
  time frame: At entry
  description: General demographic data, including age, sex (male/female), body mass index (BMI) (kg/m2), and smoking history will be recorded.
  measure: Biomarker
  time frame: At entry
  description: Serum eosinophils and hemoglobin will be measured
  measure: FeNO
  time frame: At entry
  description: Measurement of Exhaled Nitric Oxide by NOBreath
  measure: Lung function and body box
  time frame: At entry
  description: Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the percentage of FEV1 in the estimated value will be measured at baseline and after methacholine test by Vyntus, Vyaire Medical. Body plethysmography with residual volumen (RV), total lung capacity (TLC), diffusion capacity of the lungs for carbon monoxide (DLCO), will be measured before methacholine test by Medical Electronic Construction (MEC).
  measure: Asthma medication
  time frame: At entry
  description: Inhaled corticosteroids (ICS), long-acting beta2agonists (LABA), long-acting muscarinic antagonists (LAMA), Leukotriene antagonist, theophylline, and prednisolone - type and dose
  arm group label: Asthma
  description: Asthma according to Gina Guidelines
  intervention type: Other
  intervention name: No intervention
  description: No intervention
  arm group label: Asthma
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Thomas Ringbæk, MSci
  role: Principal Investigator
  affiliation: Allergy and Lung Clinic Elsinore
  last name: Thomas Ringbæk, MSci
  phone: 004521969087
  email: thomasringbaek@gmail.com
  last name: Lars Frølund, MSci
  phone: 004521777696
  email: lars.froelund@dadlnet.dk
  responsible party type: Principal Investigator
  investigator affiliation: Allergi- og Lungeklinikken, Elsinore
  investigator full name: Thomas Ringbæk
  investigator title: Principal Investigator
  mesh term: Bronchial Hyperreactivity
  sharing ipd: Undecided
  ipd description: Publication in per-reviewed papers;