Influence of Cromones on Eucapnic Hyperventilation (EVH)-Test in Young (Elite) Athletes Who Tested Positive for EIB.

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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WP3-Influence of Cromones on EVH-test in Young (Elite) Athletes Who Tested Positive for EIB (=Exercise Induced Bronchoconstriction)

Conditions
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Exercise-Induced Bronchoconstriction

Intervention / Treatment
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* Drug: Sodium Cromoglycate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of exercise-induced-bronchoconstriction (EIB) based on positive EVH-test in WP1 (s59778) or WP2 (s61602) BMI between 5th and <85th percentile for age and gender Exclusion Criteria: Clinically diagnosed asthma Baseline lung function: FEV1%: ≤80% predicted FEV1% Tiffeneau: FEV1/FVC% < 85% Salbutamol-induced FEV1 reversibility ≥ 12% Any disorder, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol Smoker Participation in other study related to IMP If applicable: female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blinded clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Cromoglycate<br>Patients will take Sodium Cromoglycate (SCG) (Lomudal®) 4 times daily during 6 months: SCG 4X1 ampulla of 2 mL daily (by Omron pocket aerosol). | Drug: Sodium Cromoglycate<br>* Sodium Cromoglicate 10 mg/mL packed in ampulla of 2 mL; Daily dosis of 4X20 mg milligram delivered by aerosol.<br>* Other names: Lomudal;|
| Placebo Comparator: Sodium Chloride 0.9%<br>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). | Drug: Placebo<br>* Sodium Chloride 0.9% packed in ampulla of 2 mL; Daily dosis of 4 ampulla delivered by aerosol.<br>* Other names: Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percentage maximal fall of FEV1 after EVH-test compared to baseline maximal fall | 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in symptom perception on a scale 0 to 5, with 5 maximum score per symptom | 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. | 6 months | 
| Asthma development | Asthma development will be assessed by the occurrence of a positive reversibility test during the trial and compared between both arms. | 6 months | 
| Biomarkers in blood/sputum (optional) | 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, ...) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Athletes, Sodium Cromoglycate, Cromones, Lomudal