An interventional study of Cold air exercise test in Asthma, Exercise-Induced, sponsored by KU Leuven. Completed at 1 site in Belgium. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-12-17.
Sponsored by KU Leuven · Not applicable, Interventional, and Basic science
The purpose of the study is to compare airway physiologic reactions to physical exercise in a cold air environment (-5°C, 60% relative humidity) between normal volunteers and subjects with mild/moderate asthma. For this purpose, the investigators intend to evaluate the effect of a cold air exercise test on the Forced Expiratory Volume in 1 second (FEV1), respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
This study also features as an exploratory study for a subsequent interventional study in order to establish the feasibility of the cold air exercise protocol and to determine the extent of the effects in subjects with mild/moderate asthma.
It is already demonstrated that exercising during cold air exposure and at a high altitude may induce asthmatic symptoms, a variable degree of airway obstruction and increased neutrophilic airway inflammation in asthmatic patients. Therefore, in this project, the investigators want to evaluate the feasibility, of a shorter standardized "cold air exercise test" (a submaximal exercise challenge in a controlled cold air (-5°C, relative humidity 60%) environment) and to compare the respiratory physiologic reactions to physical exercise during cold exposure between healthy volunteers and asthmatic patients. For this purpose, they intend to evaluate the effect of a cold air exercise test on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
This study features as an exploratory study for a subsequent interventional study, that will assess the protective effect of azithromycin versus placebo on the cold air exercise induced changes in patients with mild/moderate asthma (ALASCAIR2 study). The present preparatory study is needed to standardize the cold air exercise test in a controlled environment so that it would be possible to use it as challenge test in an interventional study and to identify the most appropriate design for such a study.
The primary objective of this study is to compare the proportional change in FEV1, pre to post a 90 minutes submaximal exercise in a cold air environment between healthy volunteers versus mild/moderate asthmatics, calculated as a time-weighted average over the 30 minutes post-exposure.
The primary endpoint is the change in FEV1, calculated as a time-weighted average over the 30 minutes after the cold exercise test. At each time point (pre-exposure, 5' post-exposure, and at 15, 25 and 35 minutes post-exposure), FEV1 (L) will be measured in triplicate.
They want to evaluate whether the exercise test in a cold air environment produces respiratory symptoms (such as nasal discharge or obstruction, dyspnea, cough and/or mucus production, etc.), has an impact on airway integrity (nasal patency, airflow obstruction, lung ventilation inhomogeneity \& small airway dysfunction, bronchial hyperreactivity, cough reflex hypersensitivity), induces local or systemic inflammatory changes (biomarkers in nasal fluid, sputum and blood) or changes to the airway microbiome (in nasal fluid and sputum) in healthy volunteers and in mild/moderate asthmatics. The study group also want to compare the observed changes induced by the cold air exercise test between the healthy volunteers and the mild/moderate asthmatics.
The secondary endpoints of this study include the observed changes in (respiratory) symptom score, Peak Nasal Inspiratory Flow (PNIF), Forced Vital Capacity (FVC), Forced Expiratory Flow (FEF25-75), Fraction of Exhaled Nitric Oxide (FeNO), histamine provocative concentration causing 20% drop in FEV1 (PC20), cough threshold C2 \& C5, sputum differential cell count, biomarkers in nasal fluid, sputum and blood, nasal and sputum microbial communities between the healthy volunteers and the mild/moderate asthmatics.
52 studies on the registry are indexed under Asthma, Exercise-Induced; 3 are open to participants now.
This study's enrollment of 45 is close to the median of 47 across 40 interventional studies indexed under Asthma, Exercise-Induced.
Browse Asthma, Exercise-Induced studies →KU Leuven is the lead sponsor of 373 studies on the registry; 65 are open to participants now.
Counted across the registry records on this site, refreshed daily.
INCLUSION CRITERIA - healthy volunteers
INCLUSION CRITERIA - asthmatic patients
EXCLUSION CRITERIA - healthy volunteers
EXCLUSION CRITERIA - asthmatics patients
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Healthy volunteers will perform the same protocol as foreseen for asthmatic patients. Both will perform the cold air exercise test with pre -and post-exposure evaluation of on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
Other: Cold air exercise test
Asthmatic patients will perform the same protocol as foreseen for healthy volunteers. They will perform the cold air exercise test with pre -and post-exposure evaluation of on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
Other: Cold air exercise test
Subjects will perform a submaximal 90 minutes exercise test in a controlled cold air environment (-5°C, 60% relative humidity) in a climate chamber with evaluation pre§/during\*/post§ of heart rate (HR)§\* and blood pressure (BP)§\*, spirometry§\*, PNIF§, FeNO§, electrocardiogram (ECG)§\*, body \& exhaled air temperature§\*, capsaicin cough threshold test§, histamine bronchial challenge test§, and sampling of nasal fluid§, induced sputum§, and venous blood§.
Change in Forced Expiratory Volume in 1 seconds (FEV1)
Change in FEV1, calculated as a time-weighted average over the 35 minutes after the cold air exercise test and 24 hours and 1 week post-exposure. A maximal fall of 10% will be considered as positive response
Time frame: pre-, 5, 15, 25 and 35 minutes, 24 hours and 1 week post-exposure
Changes in asthma control
Asthma control will be determined using the Asthma Control Questionnaire (ACQ-6), including 6 questions. Each question will be scored from 0-6 and added together. This final score will be divided by the number of questions. If ACQ-6 \< 0.75 = controlled asthma, ACQ-6 from 0.75-1.5 = partly controlled asthma and ACQ-6 \> 1.5 = uncontrolled asthma.
Time frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure
Changes in respiratory symptom score
The degree of dyspnea will be determined using Borg scale. This Borg scale is 0 to 10 rated scale. With 0 no dyspnea and 10 complete dyspnea.
Time frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure
Cough hypersensitivity
Cough hypersensitivity (Capsaicin cough threshold) will be measured using a capsaicin challenge test. The concentrations (µmol/l) which provokes 2 coughs (C2) and 10 coughs (C10) will be recorded and will be compared before and after cold air exposure.
Time frame: Pre-exposure and 24 hours and 1 week post-exposure
Bronchial hyperreactivity
Bronchial hyperreactivity will be measured using a histamine provocation. Bronchial hyperreactivity will be confirmed when there is a drop of 20% in FEV1 post histamine provocation (PC20).
Time frame: Pre-exposure and 1 week post-exposure
Nasal hyperreactivity
Nasal hyperreactivity will be measured using a PNIF measurement. Nasal hyperreactivity will be confirmed when there is a drop of 20% in PNIF.
Time frame: Pre-exposure and immediately and 24 hours post-exposure
Airway inflammation
Bronchial airway inflammation. Differential cell count will be performed on sputum samples, determining eosinophilic (\>3% eosinophils, \<61% neutrophils), neutrophilic (\<3% eosinophils and \>61% neutrophils), pauci-granulocytic (\<3% eosinophils and \<61% neutrophils) and mixed granulocytic airway inflammation (\>3% eosinophils and \>61% neutrophils).
Time frame: Pre-exposure and 24 hours and 1 week post-exposure
Cytokine pattern in the airways
Cytokines concentrations (pg/ml) will also be determined in sputum supernatant using a U-plex assay.
Time frame: Pre-exposure and 24 hours and 1 week post-exposure
Biomarkers for airway inflammation
FeNO will be used as biomarker for eosinophilic airway inflammation. FeNO \< 25 ppb = eosinophilic inflammation less likely, FeNO between 25 and 50 ppm = need further interpretation with additional clinical information, FeNO \> 50 ppm = indication of eosinophilic airway inflammation (according to the American Thoracic Society guidelines)
Time frame: Pre-exposure and 24 hours and 1 week post-exposure
Nasal inflammation
Cytokine concentrations (pg/ml) will be determined in the nasal fluid as biomarkers for nasal inflammation
Time frame: Pre-exposure and immediately and 24 hours post-exposure
Systemic inflammation
The degree of system inflammation will be determined via differential blood cell count.
Time frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure
Biomarkers for systemic inflammation
The degree of system inflammation will be determined via C-reactive protein (CRP) levels. Normal values for CRP are considered \< 10 mg/ml.
Time frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure
Changes in microbiome in lung and nose
The presence of 22 common respiratory viruses, 5 bacteria and 1 fungi will be determined using qualitative reverse transcription polymerase chain reaction (qRT-PCR) in sputum and nasal fluid. Pre and post-exposure microbiome patterns will be compared.
Time frame: Pre-exposure and 1 week post-exposure
Evaluation of the heart rate pattern
Cardiovascular health will be evaluated by determining the heart rate pattern using ECG. Deviation from a normal ECG pattern will be recorded.
Time frame: Pre-exposure and during the 90 minutes cold air exposure
Determining the exercise capacity
Exercise capacity will be checked. In a single test pre-exposure, the aerobic heart rate zone, anaerobic heart rate zone and maximal oxygen volume uptake (VO2max) heart rate zone will be evaluated to determine the exercise capacity
Time frame: Pre-exposure
Plan to share: No
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This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.
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