<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/NCT04408664</url>
  </required_header>
  <id_info>
    <org_study_id>s63147</org_study_id>
    <nct_id>NCT04408664</nct_id>
  </id_info>
  <brief_title>Influence of Cromones on Eucapnic Hyperventilation (EVH)-Test in Young (Elite) Athletes Who Tested Positive for EIB.</brief_title>
  <official_title>WP3-Influence of Cromones on EVH-test in Young (Elite) Athletes Who Tested Positive for EIB (=Exercise Induced Bronchoconstriction)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jessa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Algemeen Ziekenhuis Maria Middelares</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blinded, placebo-controlled trial of nebulized Sodium&#xD;
      Cromoglycate (SCG) (Lomudal®) versus NaCl0.9% in athletes (11-18 year) with exercise-induced&#xD;
      bronchoconstriction (EIB).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening and diagnosing EIB (studied by investigators in WP1 (s59778) and WP2 (s61602) of&#xD;
      granted FWO-TBM project (T001417N)) in young athletes would only be useful if a safe and&#xD;
      effective treatment is available. Sodium Cromoglycate (SCG) has a very nice safety profile&#xD;
      but is less effective when compared to inhaled corticosteroids in asthma patients. However,&#xD;
      SCG has been shown to be especially effective in exercise-induced asthma and to reduce&#xD;
      metabolite secretion in athletes due to hyperpnoea. Although commercial interest in the drug&#xD;
      has fainted, from a clinical point of view, it remains the ideal candidate to be used in&#xD;
      adolescents with features of EIB at risk to develop asthma in whom today no treatment would&#xD;
      be initiated.&#xD;
&#xD;
      This clinical trial (s63147), which is WP3 of the FWO-TBM project, is a randomized&#xD;
      double-blinded trial with subjects who tested positive for the diagnosis of EIB in either WP1&#xD;
      or WP2. Subjects who gave assent and whose parents gave consent will be randomized (1/1) in a&#xD;
      double-blinded trial to receive either (arm 1) Sodium Cromoglycate (SCG) (Lomudal®) or (arm&#xD;
      2) placebo, both 4X1 ampulla (2 mL) in aerosol daily, during 6 months.&#xD;
&#xD;
      During the previous trials, several tests were already performed. If subjects want to&#xD;
      participate in this trial and the previous tests were more than 1 month ago, some tests will&#xD;
      be repeated as a baseline: questionnaires, spirometry (with reversibility test) and EVH-test.&#xD;
      After 3 months, regular intake as well as potential side effects will be evaluated. After 6&#xD;
      months, in addition to questionnaires, clinical examination and spirometry with reversibility&#xD;
      test, the EVH-test will be repeated. Subjects will also be offered the possibility to repeat&#xD;
      (as they did for WP1 and WP2) a blood and sputum sampling at 6 months. Afterwards, subjects&#xD;
      will have the option to continue open-label treatment for 6 months.&#xD;
&#xD;
      The investigators want to investigate the influence of SCG on EVH-test in young athletes who&#xD;
      tested positive for EIB.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient accrual rate&#xD;
  </why_stopped>
  <start_date type="Actual">April 6, 2021</start_date>
  <completion_date type="Actual">August 1, 2023</completion_date>
  <primary_completion_date type="Actual">June 28, 2023</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Randomized double-blinded clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in percentage maximal fall of FEV1 after EVH-test compared to baseline maximal fall</measure>
    <time_frame>6 months</time_frame>
    <description>Individual's paired change in percentage maximal fall of FEV1 in relation to EVH-test between baseline values and values after 6 month treatment with sodium cromoglycate or placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in symptom perception on a scale 0 to 5, with 5 maximum score per symptom</measure>
    <time_frame>6 months</time_frame>
    <description>Symptom perception will be assessed by a questionnaire (scale: no, very mild, little, moderate, serious, very serious) . Comparison will be done per individual and between both arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma development</measure>
    <time_frame>6 months</time_frame>
    <description>Asthma development will be assessed by the occurrence of a positive reversibility test during the trial and compared between both arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers in blood/sputum (optional)</measure>
    <time_frame>6 months</time_frame>
    <description>Change in expression of inflammatory markers and markers of epithelial damage after 6 months of treatment in blood and sputum (e.g. CC16, uric acid, IL1-B, ...)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Exercise-Induced Bronchoconstriction</condition>
  <arm_group>
    <arm_group_label>Sodium Cromoglycate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will take Sodium Cromoglycate (SCG) (Lomudal®) 4 times daily during 6 months: SCG 4X1 ampulla of 2 mL daily (by Omron pocket aerosol).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium Chloride 0.9%</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will take Sodium Chloride 0.9% 4 times daily during 6 months: Sodium Chloride 4X1 ampulla of 2 mL daily (by Omron pocket aerosol).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Cromoglycate</intervention_name>
    <description>Sodium Cromoglicate 10 mg/mL packed in ampulla of 2 mL; Daily dosis of 4X20 mg milligram delivered by aerosol.</description>
    <arm_group_label>Sodium Cromoglycate</arm_group_label>
    <other_name>DNCG Iso</other_name>
    <other_name>Lomudal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sodium Chloride 0.9% packed in ampulla of 2 mL; Daily dosis of 4 ampulla delivered by aerosol.</description>
    <arm_group_label>Sodium Chloride 0.9%</arm_group_label>
    <other_name>Sodium Chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of exercise-induced-bronchoconstriction (EIB) based on positive EVH-test in&#xD;
             WP1 (s59778) or WP2 (s61602)&#xD;
&#xD;
          -  BMI between 5th and &lt;85th percentile for age and gender&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically diagnosed asthma&#xD;
&#xD;
          -  Baseline lung function:&#xD;
&#xD;
               -  FEV1%: ≤80% predicted FEV1%&#xD;
&#xD;
               -  Tiffeneau: FEV1/FVC% &lt; 85%&#xD;
&#xD;
               -  Salbutamol-induced FEV1 reversibility ≥ 12%&#xD;
&#xD;
          -  Any disorder, which in the investigator's opinion might jeopardize participant's&#xD;
             safety or compliance with the protocol&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Participation in other study related to IMP&#xD;
&#xD;
          -  If applicable: female who is pregnant, breast-feeding or intends to become pregnant or&#xD;
             is of child-bearing potential and not using an adequate contraceptive method&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams-Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Maria Middelares</name>
      <address>
        <city>Ghent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Van der Eycken S, Schelpe A, Marijsse G, Dilissen E, Troosters T, Vanbelle V, Aertgeerts S, Dupont LJ, Peers K, Bullens DM, Seys SF. Feasibility to apply eucapnic voluntary hyperventilation in young elite athletes. Respir Med. 2016 Feb;111:91-3. doi: 10.1016/j.rmed.2015.12.012. Epub 2016 Jan 4.</citation>
    <PMID>26790574</PMID>
  </reference>
  <reference>
    <citation>Jonckheere AC, Seys S, Dilissen E, Schelpe AS, Van der Eycken S, Corthout S, Verhalle T, Goossens J, Vanbelle V, Aertgeerts S, Troosters T, Peers K, Dupont L, Bullens D. Early-onset airway damage in early-career elite athletes: A risk factor for exercise-induced bronchoconstriction. J Allergy Clin Immunol. 2019 Nov;144(5):1423-1425.e9. doi: 10.1016/j.jaci.2019.07.014. Epub 2019 Jul 26. No abstract available.</citation>
    <PMID>31356920</PMID>
  </reference>
  <reference>
    <citation>Kippelen P, Larsson J, Anderson SD, Brannan JD, Dahlen B, Dahlen SE. Effect of sodium cromoglycate on mast cell mediators during hyperpnea in athletes. Med Sci Sports Exerc. 2010 Oct;42(10):1853-60. doi: 10.1249/MSS.0b013e3181da4f7d.</citation>
    <PMID>20216468</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Athletes</keyword>
  <keyword>Sodium Cromoglycate</keyword>
  <keyword>Cromones</keyword>
  <keyword>Lomudal</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cromolyn Sodium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>data will be analysed and grouped before release</ipd_description>
  </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/NCT04408664
org study id: s63147
nct id: NCT04408664
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a randomized, double-blinded, placebo-controlled trial of nebulized Sodium
      Cromoglycate (SCG) (Lomudal®) versus NaCl0.9% in athletes (11-18 year) with exercise-induced
      bronchoconstriction (EIB).
Screening and diagnosing EIB (studied by investigators in WP1 (s59778) and WP2 (s61602) of
      granted FWO-TBM project (T001417N)) in young athletes would only be useful if a safe and
      effective treatment is available. Sodium Cromoglycate (SCG) has a very nice safety profile
      but is less effective when compared to inhaled corticosteroids in asthma patients. However,
      SCG has been shown to be especially effective in exercise-induced asthma and to reduce
      metabolite secretion in athletes due to hyperpnoea. Although commercial interest in the drug
      has fainted, from a clinical point of view, it remains the ideal candidate to be used in
      adolescents with features of EIB at risk to develop asthma in whom today no treatment would
      be initiated.

      This clinical trial (s63147), which is WP3 of the FWO-TBM project, is a randomized
      double-blinded trial with subjects who tested positive for the diagnosis of EIB in either WP1
      or WP2. Subjects who gave assent and whose parents gave consent will be randomized (1/1) in a
      double-blinded trial to receive either (arm 1) Sodium Cromoglycate (SCG) (Lomudal®) or (arm
      2) placebo, both 4X1 ampulla (2 mL) in aerosol daily, during 6 months.

      During the previous trials, several tests were already performed. If subjects want to
      participate in this trial and the previous tests were more than 1 month ago, some tests will
      be repeated as a baseline: questionnaires, spirometry (with reversibility test) and EVH-test.
      After 3 months, regular intake as well as potential side effects will be evaluated. After 6
      months, in addition to questionnaires, clinical examination and spirometry with reversibility
      test, the EVH-test will be repeated. Subjects will also be offered the possibility to repeat
      (as they did for WP1 and WP2) a blood and sputum sampling at 6 months. Afterwards, subjects
      will have the option to continue open-label treatment for 6 months.

      The investigators want to investigate the influence of SCG on EVH-test in young athletes who
      tested positive for EIB.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized double-blinded clinical trial
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Change in percentage maximal fall of FEV1 after EVH-test compared to baseline maximal fall
time frame: 6 months
description: Individual's paired change in percentage maximal fall of FEV1 in relation to EVH-test between baseline values and values after 6 month treatment with sodium cromoglycate or placebo.
measure: Difference in symptom perception on a scale 0 to 5, with 5 maximum score per symptom
time frame: 6 months
description: Symptom perception will be assessed by a questionnaire (scale: no, very mild, little, moderate, serious, very serious) . Comparison will be done per individual and between both arms.
measure: Asthma development
time frame: 6 months
description: Asthma development will be assessed by the occurrence of a positive reversibility test during the trial and compared between both arms.
measure: Biomarkers in blood/sputum (optional)
time frame: 6 months
description: Change in expression of inflammatory markers and markers of epithelial damage after 6 months of treatment in blood and sputum (e.g. CC16, uric acid, IL1-B, ...)
arm group label: Sodium Cromoglycate
arm group type: Experimental
description: Patients will take Sodium Cromoglycate (SCG) (Lomudal®) 4 times daily during 6 months: SCG 4X1 ampulla of 2 mL daily (by Omron pocket aerosol).
arm group label: Sodium Chloride 0.9%
arm group type: Placebo Comparator
description: Patients will take Sodium Chloride 0.9% 4 times daily during 6 months: Sodium Chloride 4X1 ampulla of 2 mL daily (by Omron pocket aerosol).
intervention type: Drug
intervention name: Sodium Cromoglycate
description: Sodium Cromoglicate 10 mg/mL packed in ampulla of 2 mL; Daily dosis of 4X20 mg milligram delivered by aerosol.
arm group label: Sodium Cromoglycate
other name: DNCG Iso
other name: Lomudal
intervention type: Drug
intervention name: Placebo
description: Sodium Chloride 0.9% packed in ampulla of 2 mL; Daily dosis of 4 ampulla delivered by aerosol.
arm group label: Sodium Chloride 0.9%
other name: Sodium Chloride
criteria: 
gender: All
minimum age: 11 Years
maximum age: 18 Years
healthy volunteers: No
facility: 
facility: 
country: Belgium
citation: Van der Eycken S, Schelpe A, Marijsse G, Dilissen E, Troosters T, Vanbelle V, Aertgeerts S, Dupont LJ, Peers K, Bullens DM, Seys SF. Feasibility to apply eucapnic voluntary hyperventilation in young elite athletes. Respir Med. 2016 Feb;111:91-3. doi: 10.1016/j.rmed.2015.12.012. Epub 2016 Jan 4.
PMID: 26790574
citation: Jonckheere AC, Seys S, Dilissen E, Schelpe AS, Van der Eycken S, Corthout S, Verhalle T, Goossens J, Vanbelle V, Aertgeerts S, Troosters T, Peers K, Dupont L, Bullens D. Early-onset airway damage in early-career elite athletes: A risk factor for exercise-induced bronchoconstriction. J Allergy Clin Immunol. 2019 Nov;144(5):1423-1425.e9. doi: 10.1016/j.jaci.2019.07.014. Epub 2019 Jul 26. No abstract available.
PMID: 31356920
citation: Kippelen P, Larsson J, Anderson SD, Brannan JD, Dahlen B, Dahlen SE. Effect of sodium cromoglycate on mast cell mediators during hyperpnea in athletes. Med Sci Sports Exerc. 2010 Oct;42(10):1853-60. doi: 10.1249/MSS.0b013e3181da4f7d.
PMID: 20216468
responsible party type: Sponsor
mesh term: Cromolyn Sodium
sharing ipd: No
ipd description: data will be analysed and grouped before release