AsthmaPhase 4NCT03105843
Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol
A Phase 4 study testing Methacholine (MCh) Challenge Testing, Eucapneic Voluntary Hyperventilation (EVH) and Mannitol Inhalation Kit in people with Asthma and Cough, run by Dr. Diane Lougheed at 1 site in Canada.
Trial summary
The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Cough, Cough Variant Asthma
- What is being tested?
- Methacholine (MCh) Challenge Testing, Eucapneic Voluntary Hyperventilation (EVH) and Mannitol Inhalation Kit
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- 1 Mar 2022to 31 Jul 2026
- Phase
- Phase 4
- 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
- Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
- CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
- Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).
- Individuals aged 18-65 years of age with no history of asthma or chronic cough.
Who cannot join
- an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
- inability to perform acceptable spirometry
- medical contraindications to methacholine challenge testing
- smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol in Individuals With Cough Variant Asthma and Chronic Cough
The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough.
We hypothesize:
- EVH and Mannitol cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls.
- The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).
Read the detailed description
Asthma is a chronic respiratory condition characterized by eosinophilic airway inflammation. Individuals with classic asthma experience paroxysmal symptoms including cough, wheeze, shortness of breath and chest tightness. Cough variant asthma (CVA) is asthma in which chronic cough (cough lasting eight weeks or more) is the sole or predominant symptom of asthma. The pathophysiologic mechanisms which differentiate asthma, CVA, and eosinophilic bronchitis without asthma are not fully understood. We have recently identified individuals with chronic cough who cough during methacholine but have normal airway sensitivity (ie. do not have asthma or CVA) (COUGH) and may or may not have eosinophilic bronchitis. The purpose of this research is to further explore the pathophysiologic basis for cough in these conditions using two 'indirect' inhalation challenge tests: eucapneic voluntary hyperventilation (EVH) and Mannitol), which induce osmotic and/or temperature changes in airway. Specifically, this study will collect preliminary data on the sensory-mechanical responses of individuals with CVA, COUGH and healthy controls to EVH and Mannitol Challenges.
- Conditions
- Asthma, Cough, Cough Variant Asthma
- Being tested
- Methacholine (MCh) Challenge Testing, Eucapneic Voluntary Hyperventilation (EVH), Mannitol Inhalation Kit
- Keywords
- Asthma, Cough, Eucapneic Voluntary Hyperventilation, Hypertonic Saline
- Medical subject headings
- Asthma, Cough, Cough-Variant Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methacholine (MCh) Challenge TestingDrug
Also called MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)], Provocholine
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Eucapneic Voluntary Hyperventilation (EVH)Diagnostic test
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Mannitol Inhalation KitDrug
Also called Mannitol Challenge Test
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
| Study group | Role | What they receive |
|---|---|---|
| Cough Variant Asthma | Experimental | Individuals diagnosed with Cough variant asthma Receives: Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit |
| Methacholine-induced cough | Experimental | Individuals with chronic cough and negative methacholine challenge Receives: Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit |
| Control | Experimental | Individuals with no history of asthma or chronic cough Receives: Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mid expiratory flows
The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.
Measured: Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test
Secondary outcomes (5)
Respiratory System Reactance (X5)
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Measured: After dose administration; will occur 2-5 minutes after dose
Peripheral Resistance (R5-R20)
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Measured: After dose administration; will occur 2-5 minutes after dose
Central Airway Resistance
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Measured: After dose administration; will occur 2-5 minutes after dose
Forced Vital Capacity (FVC)
As an index of airway closure.
Measured: After dose administration; will occur 2-5 minutes after dose
FEV1/FVC
As an index of airway obstruction.
Measured: After dose administration; will occur 2-5 minutes after dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2017
- Study start1 Mar 2022
- Primary completion31 Jul 2026
- Study completion31 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Diane Lougheed
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Diane Lougheed, Queen's University
- Investigators
- M. Diane Lougheed, MD, MSc, Principal investigator, Department of Medicine, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03105843
- Sponsor's protocol ID
- 2023-17
- Status last verified
- Aug 2026
- First submitted
- 4 Apr 2017
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol in Individuals With Cough Variant Asthma and Chronic Cough
- ClinicalTrials.gov ID
- NCT03105843
- Acronym / sponsor ID
- 2023-17
- Conditions
- Asthma, Cough, Cough Variant Asthma
- Keywords
- Asthma, Cough, Eucapneic Voluntary Hyperventilation, Hypertonic Saline
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Dr. Diane LougheedUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 31 Jul 2026 (actual)
- Study completion
- 31 Jul 2026 (actual)
- First posted
- 10 Apr 2017 (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.
The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough.
We hypothesize:
- EVH and Mannitol cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls.
- The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).
Detailed description
Asthma is a chronic respiratory condition characterized by eosinophilic airway inflammation. Individuals with classic asthma experience paroxysmal symptoms including cough, wheeze, shortness of breath and chest tightness. Cough variant asthma (CVA) is asthma in which chronic cough (cough lasting eight weeks or more) is the sole or predominant symptom of asthma. The pathophysiologic mechanisms which differentiate asthma, CVA, and eosinophilic bronchitis without asthma are not fully understood. We have recently identified individuals with chronic cough who cough during methacholine but have normal airway sensitivity (ie. do not have asthma or CVA) (COUGH) and may or may not have eosinophilic bronchitis. The purpose of this research is to further explore the pathophysiologic basis for cough in these conditions using two 'indirect' inhalation challenge tests: eucapneic voluntary hyperventilation (EVH) and Mannitol), which induce osmotic and/or temperature changes in airway. Specifically, this study will collect preliminary data on the sensory-mechanical responses of individuals with CVA, COUGH and healthy controls to EVH and Mannitol Challenges.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cough Variant Asthma | Experimental | Drug: Methacholine (MCh) Challenge Testing, Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH), Drug: Mannitol Inhalation KitIndividuals diagnosed with Cough variant asthma |
| Methacholine-induced cough | Experimental | Drug: Methacholine (MCh) Challenge Testing, Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH), Drug: Mannitol Inhalation KitIndividuals with chronic cough and negative methacholine challenge |
| Control | Experimental | Drug: Methacholine (MCh) Challenge Testing, Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH), Drug: Mannitol Inhalation KitIndividuals with no history of asthma or chronic cough |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
- Individuals aged 18-65 years of age with no history of asthma or chronic cough.
Key exclusion criteria (4 listed)
- an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
- inability to perform acceptable spirometry
- medical contraindications to methacholine challenge testing
- smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.
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 |
|---|---|---|
| Methacholine (MCh) Challenge TestingAlso: MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)], ProvocholineVisit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops. | Drug | Control, Cough Variant Asthma, Methacholine-induced cough |
| Eucapneic Voluntary Hyperventilation (EVH)Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit. | Diagnostic test | Control, Cough Variant Asthma, Methacholine-induced cough |
| Mannitol Inhalation KitAlso: Mannitol Challenge TestVisit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit. | Drug | Control, Cough Variant Asthma, Methacholine-induced cough |
Primary outcome
Mid expiratory flows
Time frame: Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test
The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.
5 secondary outcomes
Respiratory System Reactance (X5)
Time frame: After dose administration; will occur 2-5 minutes after dose
Peripheral Resistance (R5-R20)
Time frame: After dose administration; will occur 2-5 minutes after dose
Central Airway Resistance
Time frame: After dose administration; will occur 2-5 minutes after dose
Forced Vital Capacity (FVC)
Time frame: After dose administration; will occur 2-5 minutes after dose
FEV1/FVC
Time frame: After dose administration; will occur 2-5 minutes after dose
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 12 Aug 2026.
- Individual participant dataSharing planned: No
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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.
M. Diane Lougheed, MD, MSc principal investigator
Department of Medicine, Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methacholine (MCh) Challenge Testing, Eucapneic Voluntary Hyperventilation (EVH) and Mannitol Inhalation Kit in people with Asthma and Cough, run by Dr. Diane Lougheed at 1 site in Canada.
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 4 inclusion and 4 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 12 Aug 2026. 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 Canada. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Mid expiratory flows (time frame: Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test). 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 12 Aug 2026.