AsthmaNCT01659476
Bronchodilating and Bronchoprotective Effects of Deep Inspirations
A study testing Methacholine(MCh) Challenge Testing in people with Asthma and Cough, run by Queen's University at 1 site in Canada.
Trial summary
The objectives of this research are to compare (i) the bronchodilating and (ii) the bronchoprotective effects of deep inspirations (DIs) in individuals with: (a) asthma, (b) CVA, (c) methacholine-induced cough but normal airway sensitivity and . Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- What is being tested?
- Methacholine(MCh) Challenge Testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2012to Aug 2017
- 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
- Individuals aged 18-65 years of age with asthma, CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
- asthma: episodic respiratory symptoms occurring in association with variable airflow obstruction (Canadian Asthma Consensus Report definition);
- 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
- Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
- Heart attack or stroke in last 3 months;
- Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
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- Known aortic aneurysm;
- Moderate airflow limitation <60% predicted or 1.5) is a relative contraindication;
- Inability to perform acceptable quality spirometry;
- Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
- Pregnant or nursing mothers.
- 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.
Canada1 site
Kingston General Hospital at Queen's University
Kingston, Ontario, K7L 2V7
About this study
Official title: Bronchodilating and Bronchoprotective Effects of Deep Inspirations in Asthma, Cough Variant Asthma and Chronic Cough With Normal Airway Sensitivity and Sensory-Mechanical Responses to High-Dose Methacholine in Healthy Normal Subjects
The objectives of this research are to compare (i) the bronchodilating and (ii) the bronchoprotective effects of deep inspirations (DIs) in individuals with: (a) asthma, (b) CVA, (c) methacholine-induced cough but normal airway sensitivity and .
(d) in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).
Read more
Hypotheses:
- The bronchodilating effect of a DI will be: (a) absent or impaired in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in individuals with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness). ii. The bronchoprotective effect of a DI will be: (a) absent in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in those with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness). iii. Healthy individuals without asthma, chronic cough, or asymptomatic airway hyperresponsiveness, will not cough, or develop significant dyspnea, small airways obstruction or dynamic hyperinflation during high-dose methacholine bronchoprovocation.
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) and may or may not have eosinophilic bronchitis. The purpose of this research is to examine the pathophysiologic differences between three causes of chronic cough: asthma, cough variant asthma and methacholine-induced cough with normal airway sensitivity. The responses in healthy normal subjects are crucial to understand the clinical relevance of methacholine-induced cough with normal airway sensitivity.
- Being tested
- Methacholine(MCh) Challenge Testing
- Keywords
- methacholine, deep inspiration, bronchoprotective effect, bronchodilating effect
- Medical subject headings
- Asthma, Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methacholine(MCh) Challenge TestingOther
Also called Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)], Other names: Provocholine
Visit 1: High-dose methacholine challenge test
Visit 2 or 3: Will be conducted in random order and subjects will perform one of two modified single-dose methacholine challenge tests at either visit. During these modified challenges, subjects will (a) perform five DIs from functional residual capacity (FRC) to total lung capacity (TLC) back to FRC, or (b) refrain from taking DIs prior to inhaling the previously measured single PC20 dose of methacholine.
Methacholine(MCh) Challenge TestingOther
Also called Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)], Other names: Provocholine
Visit 1: Baseline tests, and subjects will be randomized to complete either a high-dose methacholine using maximal expiratory flow-volume loop (MEFV), or a high-dose methacholine challenge with impulse oscillometry (IOS) and partial expiratory flow-volume loop (PEFV) and MEFV at each dose step.
Visit 2: Subjects will perform the opposite protocol, based on their first visit:
| Study group | Role | What they receive |
|---|---|---|
| Asthma | Experimental | Individuals diagnosed with asthma. Receives: Other: Methacholine(MCh) Challenge Testing |
| Cough Variant Asthma | Experimental | Individuals diagnosed with cough variant asthma. Receives: Other: Methacholine(MCh) Challenge Testing |
| Mch-induced cough w/normal airway sensitivity | Experimental | Individuals with chronic cough normal PC20 MCh(>16 mg/mL) \& who cough during Mch challenge testing. Receives: Other: Methacholine(MCh) Challenge Testing |
| Normal | Experimental | Individuals with no history of asthma or chronic cough Receives: Other: Methacholine(MCh) Challenge Testing |
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 high-dose methacholine challenge testing (Visit 1) 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 PC20 and PC50 with that recorded at baseline.
Measured: Time frame of the methacholine challenge varies between individuals. At provocative concentration of methacholine causing a 20% and 50% decline in FEV1 (PC20 and PC50 respectively). On average, these occur about 15-25 minutes into the challenge test.
Secondary outcomes (6)
percent fall in FEV1
The bronchoprotective effect of a deep inspiration will be measured by the difference between the percent fall in FEV1 following administration of methacholine using modified single-dose methacholine challenge tests on Visits 2 and 3 (with or without preceding deep inspirations)
Measured: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
respiratory system reactance (X5)
The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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 methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
peripheral resistance (R5-R20)
The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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 methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Central airway resistance
The bronchoprotective effect of a DI will be also examined by comparing mechanical responses to methacholine using impulse oscillometry (IOS). 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 methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Forced vital capacity (FVC)
As an index of airway closure.
Measured: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
FEV1/FVC
As an index of airway narrowing (obstruction)
Measured: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionAug 2017
- Study completionAug 2017
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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Diane Lougheed, Queen's University
- Investigators
- M. Diane Lougheed, MD MSc, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01659476
- Sponsor's protocol ID
- 2012-01
- Status last verified
- Apr 2018
- First submitted
- 30 Jul 2012
- Last updated
- 6 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bronchodilating and Bronchoprotective Effects of Deep Inspirations in Asthma, Cough Variant Asthma and Chronic Cough With Normal Airway Sensitivity and Sensory-Mechanical Responses to High-Dose Methacholine in Healthy Normal Subjects
- ClinicalTrials.gov ID
- NCT01659476
- Acronym / sponsor ID
- 2012-01
- Keywords
- methacholine, deep inspiration, bronchoprotective effect, bronchodilating effect
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 7 Aug 2012 (estimated)
- 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 research are to compare (i) the bronchodilating and (ii) the bronchoprotective effects of deep inspirations (DIs) in individuals with: (a) asthma, (b) CVA, (c) methacholine-induced cough but normal airway sensitivity and .
(d) in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).
Hypotheses:
- The bronchodilating effect of a DI will be: (a) absent or impaired in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in individuals with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness). ii. The bronchoprotective effect of a DI will be: (a) absent in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in those with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness). iii. Healthy individuals without asthma, chronic cough, or asymptomatic airway hyperresponsiveness, will not cough, or develop significant dyspnea, small airways obstruction or dynamic hyperinflation during high-dose methacholine bronchoprovocation.
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) and may or may not have eosinophilic bronchitis. The purpose of this research is to examine the pathophysiologic differences between three causes of chronic cough: asthma, cough variant asthma and methacholine-induced cough with normal airway sensitivity. The responses in healthy normal subjects are crucial to understand the clinical relevance of methacholine-induced cough with normal airway sensitivity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Asthma | Experimental | Other: Methacholine(MCh) Challenge TestingIndividuals diagnosed with asthma. |
| Cough Variant Asthma | Experimental | Other: Methacholine(MCh) Challenge TestingIndividuals diagnosed with cough variant asthma. |
| Mch-induced cough w/normal airway sensitivity | Experimental | Other: Methacholine(MCh) Challenge TestingIndividuals with chronic cough normal PC20 MCh(>16 mg/mL) \& who cough during Mch challenge testing. |
| Normal | Experimental | Other: Methacholine(MCh) Challenge TestingIndividuals 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 (5 listed)
- Individuals aged 18-65 years of age with asthma, 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 (13 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: Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)], Other names: ProvocholineVisit 1: High-dose methacholine challenge test Visit 2 or 3: Will be conducted in random order and subjects will perform one of two modified single-dose methacholine challenge tests at either visit. During these modified challenges, subjects will (a) perform five DIs from functional residual capacity (FRC) to total lung capacity (TLC) back to FRC, or (b) refrain from taking DIs prior to inhaling the previously measured single PC20 dose of methacholine. | Other | Asthma, Cough Variant Asthma, Mch-induced cough w/normal airway sensitivity |
| Methacholine(MCh) Challenge TestingAlso: Drug:MCh[inhalation of sequential doubling doses of MCh(0.0625-256 mg/mL)], Other names: ProvocholineVisit 1: Baseline tests, and subjects will be randomized to complete either a high-dose methacholine using maximal expiratory flow-volume loop (MEFV), or a high-dose methacholine challenge with impulse oscillometry (IOS) and partial expiratory flow-volume loop (PEFV) and MEFV at each dose step. Visit 2: Subjects will perform the opposite protocol, based on their first visit: | Other | Normal |
Primary outcome
Mid expiratory flows
Time frame: Time frame of the methacholine challenge varies between individuals. At provocative concentration of methacholine causing a 20% and 50% decline in FEV1 (PC20 and PC50 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 high-dose methacholine challenge testing (Visit 1) 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 PC20 and PC50 with that recorded at baseline.
6 secondary outcomes
percent fall in FEV1
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
respiratory system reactance (X5)
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
peripheral resistance (R5-R20)
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Central airway resistance
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
Forced vital capacity (FVC)
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
FEV1/FVC
Time frame: After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.
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 6 Apr 2018.
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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
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 study testing Methacholine(MCh) Challenge Testing in people with Asthma and Cough, run by Queen's University 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 5 inclusion and 13 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 6 Apr 2018. 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.
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 concentration of methacholine causing a 20% and 50% decline in FEV1 (PC20 and PC50 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 6 Apr 2018.