Asthma (Diagnosis)CLARINETNCT07220928
The Effect of a Cold Air Eucapnic Hyperventilation Test on Lower Respiratory Airways in Healthy Volunteers and Patients With Asthma
A study testing Cold air challenge in people with Asthma (Diagnosis), run by KU Leuven at 1 site in Belgium.
Trial summary
In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma (Diagnosis)
- What is being tested?
- Cold air challenge
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- 4 Aug 2023to 27 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 and 65 years old at time of signing informed consent
- BMI between 18 and 28 kg/cm2
- Ability to give informed consent and to comply with study protocol, in the investigator's judgement
- Non-smoking or ex-smokers for at least 12 months with less than 10 pack years
- Normal spirometry
- Group specific:
Show all 13Show fewer
- Histamine positive healthy controls: histamine bronchial challenge test (< 8 mg/ml) at screening Healthy controls: histamine bronchial challenge test (≥ 8 mg/ml) at screening
- Patients with asthma:
- Physician-diagnosed asthma for at least 6 months
- Post-bronchodilator FEV1 of ≥ 80% at screening
- Documented airway reversibility either by means of post-bronchodilator reversibility of ≥ 12.% and ≥ 200 ml or in the previous 6 months or by means of documented airway hyperresponsiveness (histamine PC20 < 4 mg/ml) at screening
- Asthma control questionnaire (ACQ) ≤ 1.5
- Regular treatment with ICS with or without LABA (unchanged dose for at least 30 days) at a low or medium dose of ICS
Who cannot join
- Previous history of intubation or admission to ICU due to asthma
- Severe asthma exacerbation within one month prior to screening visit
- Treatment with oral or systemic steroids within one month prior to screening visit
- Previous treatment with biologics for asthma
- Other major concurrent pulmonary (such as COPD, cystic fibrosis, sarcoidosis, interstitial lung disease, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, bronchiectasis) or cardiovascular disease
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory phenotype induced by cold air inhalation differs between subjects with asthma and healthy subjects. Furthermore, we want to evaluate whether the CAEH test is more robust over time compared to the EVH test. Previously, our lab has demonstrated that submaximal exercise at subfreezing temperatures in a climate chamber (-5°C) induces an acute respiratory response in patients with asthma and in healthy subjects who have been exposed to high PM10 (unpublished data). Finally, This study will serve as a preliminary study for a subsequent prospective study in which the results and optimized protocol obtained in this study will be used to further evaluate the feasibility of using this CAEH as a diagnostic tool in asthma compared to EIB (CLARINET2). The present study is required to develop a standardized CAEH test in a safe and feasible manner. This study will also help to identify appropriate endpoints (FEV1, multiple breath washout test, biomarkers…) of the subsequent studies.
Read the detailed description
In this study, we aim to develop a safe and feasible cold air (-15°C) eucapnic hyperventilation (CAEH) test protocol in which we can compare the lower airway responses between healthy volunteers and subjects with asthma. Consequently, we want to evaluate the effect of cold air inhalation on FEV1, respiratory symptoms, airway integrity, and local and systemic inflammation.
Primary endpoints
The primary endpoint of this study is to compare proportional change in FEV1, (% decrease) after a CAEH test in healthy volunteers and patients with mild to moderate asthma. Post-exposure will be calculated as a time-weighted average over the 30 min after the CAEH test. At each time point (pre-, 5, 10, 15, and 30 minutes post-exposure), FEV1 will be measured in triplicate.
Secondary endpoints
We want to evaluate whether and to what extent the inhalation of cold air during this CAEH test can induce changes in respiratory symptoms (including dyspnea, cough, mucus production, etc.), affects lower airway integrity (airway obstruction (FEV1/FVC), small airway dysfunction (FEF 25/75, lung ventilation inhomogeneity (LCI), bronchial hyperreactivity (PC20 AMP)) and whether it induces (local or systemic) inflammation (different biomarkers in sputum and blood, as defined in section 5.2).
These changes will be compared between healthy volunteers and predisposed subjects with mild to moderate asthma. The abovementioned responses and the proportional change in FEV1 after the CAEH test will be compared to a standard (21°C room air) eucapnic hyperventilation (EVH) test. Furthermore, we will compare the results obtained in this study to the results obtained in the ALASCAIR study of dr. Tatjana Decaesteker. Finally, the effects of the CAEH will be correlated to the amount of air pollution the subject was exposed to, in the days prior to the test (as this may have an effect on the responses to cold air inhalation in healthy volunteers, as found in the Alascair study (unpublished data)), by means of different questionnaires evaluating life style and exposure to air pollution (SF-36, AQLQ, ACQ, SQUASH,…).
- Conditions
- Asthma (Diagnosis)
- Being tested
- Cold air challenge
- Keywords
- Cold air hyperventilation, Asthma diagnosis
- Medical subject headings
- Asthma, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cold air challengeDevice
Also called Cold air hyperventilation test
This intervention consists of a standardized cold air eucapnic hyperventilation test using a device that controls temperature, humidity, and ventilation. Airway responses are measured via spirometry and biospecimens (serum and sputum supernatant). It is distinguished from other studies by its prospective design and inclusion of both healthy and asthmatic participants
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers with negative histamine provocation challenge | Other | Healthy volunteers with negative histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation Receives: Device: Cold air challenge |
| Healthy volunteers with positive histamine provocation challenge | Other | Healthy volunteers with positive histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation Receives: Device: Cold air challenge |
| Patients with asthma | Other | Patients with asthma will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation Receives: Device: Cold air challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportional change in FEV1 after hyperventilation challenge
The proportional change in FEV1 after hyperventilation challenges compared to baseline were measured.
Measured: After each hyperventilation challenge: pre, immediately, 3, 5, 10, 15 and 30 minutes after the challenge
Secondary outcomes (3)
Changes in symptoms
We want to evaluate changes in respiratory symptoms after challenge. The degree of dyspnea and cough will be determined using BORG scale. This is a 0 to 10 scale.
Measured: From the first hyperventilation challenge until 1 day after the second
Lung function changes
Changes in lung function (FEV1/FVC, FEF25-75, LCI, PEF...) were measured after hyperventilation challenge
Measured: After each hyperventilation challenge
Inflammatory parameters
Inflammation was assessed in sputum and blood. Cytokines, allergic response, cellular response, DAMPs and measures of epithelial integrity were assessed.
Differential cell count will be performed on sputum samples, determining eosinophilic (> 3% eosinophils), neutrophilic (> 61% neutrophils), pauci-granulocytic (< 3% eosinophilic, < 61% neutrophils) and mixed granulocytic (> 3% eosinophilic, > 61% neutrophils). Cytokines will be determined in sputum supernatant with a U-plex assay. Airway inflammation is determined with FeNO. < 25 ppm = eosinophilic inflammation less likely, between 25 - 50 ppm = need further interpretation with additional information and > 50 ppm = indication of eosinophilic airway inflammation. Systemic inflammation will be measured in serum using U-plex assay. allergic response is measured with skin prick automated test on 10 allergens and in serum with total IgE.
Measured: At baseline and after each hyperventilation challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2025
- Study start4 Aug 2023
- Primary completion27 Nov 2024
- Study completion27 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthma (Diagnosis)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Healthy volunteers will be compared to patients with astma
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Responsible party
- Principal investigator, Lieven Dupont, KU Leuven
- Investigators
- Lieven Dupont, Principal investigator, KU Leuven/UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07220928
- Sponsor's protocol ID
- S66825
- Acronym
- CLARINET
- Status last verified
- Oct 2025
- First submitted
- 23 Oct 2025
- Last updated
- 24 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of a Cold Air Eucapnic Hyperventilation Test on Lower Respiratory Airways in Healthy Volunteers and Patients With Asthma
- ClinicalTrials.gov ID
- NCT07220928
- Acronym / sponsor ID
- CLARINET / S66825
- Conditions
- Asthma (Diagnosis)
- Keywords
- Cold air hyperventilation, Asthma diagnosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Study start
- 4 Aug 2023 (actual)
- Primary completion
- 27 Nov 2024 (actual)
- Study completion
- 27 Nov 2024 (actual)
- First posted
- 24 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory phenotype induced by cold air inhalation differs between subjects with asthma and healthy subjects. Furthermore, we want to evaluate whether the CAEH test is more robust over time compared to the EVH test. Previously, our lab has demonstrated that submaximal exercise at subfreezing temperatures in a climate chamber (-5°C) induces an acute respiratory response in patients with asthma and in healthy subjects who have been exposed to high PM10 (unpublished data). Finally, This study will serve as a preliminary study for a subsequent prospective study in which the results and optimized protocol obtained in this study will be used to further evaluate the feasibility of using this CAEH as a diagnostic tool in asthma compared to EIB (CLARINET2). The present study is required to develop a standardized CAEH test in a safe and feasible manner. This study will also help to identify appropriate endpoints (FEV1, multiple breath washout test, biomarkers…) of the subsequent studies.
Detailed description
In this study, we aim to develop a safe and feasible cold air (-15°C) eucapnic hyperventilation (CAEH) test protocol in which we can compare the lower airway responses between healthy volunteers and subjects with asthma. Consequently, we want to evaluate the effect of cold air inhalation on FEV1, respiratory symptoms, airway integrity, and local and systemic inflammation.
Primary endpoints
The primary endpoint of this study is to compare proportional change in FEV1, (% decrease) after a CAEH test in healthy volunteers and patients with mild to moderate asthma. Post-exposure will be calculated as a time-weighted average over the 30 min after the CAEH test. At each time point (pre-, 5, 10, 15, and 30 minutes post-exposure), FEV1 will be measured in triplicate.
Secondary endpoints
We want to evaluate whether and to what extent the inhalation of cold air during this CAEH test can induce changes in respiratory symptoms (including dyspnea, cough, mucus production, etc.), affects lower airway integrity (airway obstruction (FEV1/FVC), small airway dysfunction (FEF 25/75, lung ventilation inhomogeneity (LCI), bronchial hyperreactivity (PC20 AMP)) and whether it induces (local or systemic) inflammation (different biomarkers in sputum and blood, as defined in section 5.2).
These changes will be compared between healthy volunteers and predisposed subjects with mild to moderate asthma. The abovementioned responses and the proportional change in FEV1 after the CAEH test will be compared to a standard (21°C room air) eucapnic hyperventilation (EVH) test. Furthermore, we will compare the results obtained in this study to the results obtained in the ALASCAIR study of dr. Tatjana Decaesteker. Finally, the effects of the CAEH will be correlated to the amount of air pollution the subject was exposed to, in the days prior to the test (as this may have an effect on the responses to cold air inhalation in healthy volunteers, as found in the Alascair study (unpublished data)), by means of different questionnaires evaluating life style and exposure to air pollution (SF-36, AQLQ, ACQ, SQUASH,…).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Healthy volunteers will be compared to patients with astma
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers with negative histamine provocation challenge | Other | Device: Cold air challengeHealthy volunteers with negative histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation |
| Healthy volunteers with positive histamine provocation challenge | Other | Device: Cold air challengeHealthy volunteers with positive histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation |
| Patients with asthma | Other | Device: Cold air challengePatients with asthma will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age between 18 and 65 years old at time of signing informed consent
- BMI between 18 and 28 kg/cm2
- Ability to give informed consent and to comply with study protocol, in the investigator's judgement
- Non-smoking or ex-smokers for at least 12 months with less than 10 pack years
- Normal spirometry
Key exclusion criteria (6 listed)
- Previous history of intubation or admission to ICU due to asthma
- Severe asthma exacerbation within one month prior to screening visit
- Treatment with oral or systemic steroids within one month prior to screening visit
- Previous treatment with biologics for asthma
- Other major concurrent pulmonary (such as COPD, cystic fibrosis, sarcoidosis, interstitial lung disease, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, bronchiectasis) or cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cold air challengeAlso: Cold air hyperventilation testThis intervention consists of a standardized cold air eucapnic hyperventilation test using a device that controls temperature, humidity, and ventilation. Airway responses are measured via spirometry and biospecimens (serum and sputum supernatant). It is distinguished from other studies by its prospective design and inclusion of both healthy and asthmatic participants | Device | Healthy volunteers with negative histamine provocation challenge, Healthy volunteers with positive histamine provocation challenge, Patients with asthma |
Primary outcome
Proportional change in FEV1 after hyperventilation challenge
Time frame: After each hyperventilation challenge: pre, immediately, 3, 5, 10, 15 and 30 minutes after the challenge
The proportional change in FEV1 after hyperventilation challenges compared to baseline were measured.
3 secondary outcomes
Changes in symptoms
Time frame: From the first hyperventilation challenge until 1 day after the second
Lung function changes
Time frame: After each hyperventilation challenge
Inflammatory parameters
Time frame: At baseline and after each hyperventilation challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2025.
- Individual participant dataSharing planned: No
Related trials for Asthma (Diagnosis)
Recruiting
Lungs on Fire: Wildfire Smoke, Incident Diseases, Susceptible Populations, and Community Values in Canada
Asthma, Chronic Obstructive Pulmonary Disease (COPD)
RecruitingObservational study
Study of the Effect of Innate on the Inflammatory Response to Endotoxin
Asthma, Atherosclerosis
Not yet recruitingObservational study
Prevelance of Broncial Asthma and Allergic Rhinitis in Children With Nephrotic Syndrim
Bronchial Asthma, Allergic Rhinitis
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 2
A Dose Finding Study With an Anti-TSLP Antibody (GSK5784283) in Adults Aged 18 to 75 Years of Age With Uncontrolled Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lieven Dupont principal investigator
KU Leuven/UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cold air challenge in people with Asthma (Diagnosis), run by KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportional change in FEV1 after hyperventilation challenge (time frame: After each hyperventilation challenge: pre, immediately, 3, 5, 10, 15 and 30 minutes after the challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.