AsthmaMICCNCT03620422
Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma
A study testing Mannitol, Salbutamol 5mg/mL and Sodium Chloride 0.9% Inhl 3Ml in people with Asthma and Cough, run by McMaster University at 1 site in Canada.
Trial summary
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing reproducibly in mild allergic asthmatics compared with healthy controls and if salbutamol can affect this. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- What is being tested?
- Mannitol, Salbutamol 5mg/mL and Sodium Chloride 0.9% Inhl 3Ml
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 11 Jan 2019to 31 Jan 2020
- 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
- Able to understand and give written informed consent
- Male and female volunteers 18 through 65 years of age.
- Positive skin-prick test to common aeroallergens (mild allergic asthmatic subjects)
- Asthma as determined by methacholine provocative concentration causing a 20% fall (PC20) ≤16 mg/ml for mild allergic asthmatic subjects; no airway hyperresponsiveness as determined by methacholine PC20>16mg/ml for normal healthy controls.
- Baseline FEV1 ≥ 70% of the predicted value for mild allergic asthmatic subjects; baseline FEV1≥ 80% of the predicted value for normal healthy controls.
- Demonstrate cough response to inhaled mannitol
Who cannot join
- Current or former smoker with >10-pack-year history
- Current or previous history of other significant respiratory disease
- Significant systemic disease, including history of current malignancy or autoimmune disease
- Asthma exacerbation or upper/lower respiratory tract infection within the previous 8 weeks
- Pregnancy
- Use of corticosteroids within 28 days prior to the first study visit.
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- Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
- Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
- Chronic use of other medication for treatment of allergic lung disease other than short-acting β2-agonists.
- Use of caffeine-containing products within 4 hours of study visits
- Use of Angiotensin converting enzyme inhibitors (ACE inhibitors)
- Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex including but not restricted to tricyclic anti-depressants, pregabalin, gabapentin, codeine, tramadol, or any other opioid.
- Lung disease other than mild to moderate allergic asthma, for mild allergic asthmatic subjects; no lung disease for normal healthy controls.
- Unwillingness or inability to comply with the study protocol for any other reason.
Trial locations and contacts
1 site in 1 country.
About this study
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing reproducibly in mild allergic asthmatics compared with healthy controls and if salbutamol can affect this. Phase 1 of this study is a reproducibility analysis of cough dose response to mannitol in a cohort of mild allergic asthmatics and healthy controls. Phase 2 is a double-blind, placebo-controlled analysis in mild allergic asthmatics assessing the effects of salbutamol on mannitol induced cough.
Read the detailed description
The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits will determine eligibility. All eligible subjects will be invited back for a third visit, and only subjects with mild allergic asthma will be invited back for a fourth visit.
Screening Period (Visits 1 and 2) - For All Subjects Eligible subjects will be identified during the initial screening procedures with measures of spirometry, hyperresponsiveness to methacholine, complete history, physical examination, allergen skin test, and mannitol cough challenge. The screening procedures will be conducted over 2 separate visits.
Reproducibility (Visit 3) - For Healthy Controls Ten normal healthy controls meeting study eligibility will return for visit 3. This visit must be at least 24h after the mannitol test at visit 1. These data will be used for assessing reproducibility of the mannitol induced coughs; Emax and the median effective dose (ED50).
Effects of Salbutamol (Visit 3 and 4) - For Mild Allergic Asthma Subjects Ten subjects with mild allergic asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Mild allergic asthmatics will first receive salbutamol 2.5mg or saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the previous mannitol cough challenges. These data will be used for determining the effects of salbutamol on mannitol-induced bronchoconstriction and cough.
Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visits 2 at the same time of day ± 2 hours
- Being tested
- Mannitol, Salbutamol 5mg/mL, Sodium Chloride 0.9% Inhl 3Ml
- Keywords
- Mannitol, Bronchoconstriction, Airway nerve function, Cough, Diagnostic Test, Osmolarity, Salbutamol
- Medical subject headings
- Asthma, Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MannitolOther
Also called Aridol
Mannitol-Induced Cough Challenge
Salbutamol 5mg/mLDrug
Also called Active Comparator
Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge
Sodium Chloride 0.9% Inhl 3MlOther
Also called Placebo Comparator
Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Other | Mannitol-Induced Cough Challenges on Visit 2 and 3. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Receives: Other: Mannitol |
| Mild Allergic Asthmatics (Saline) | Placebo comparator | Mannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized placebo (Sodium Chloride 0.9% Inhl 3Ml) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Receives: Other: Mannitol; Other: Sodium Chloride 0.9% Inhl 3Ml |
| Mild Allergic Asthmatics (Salbutamol) | Active comparator | Mannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Receives: Other: Mannitol; Drug: Salbutamol 5mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
ED50 dose response curve
Median effective dose
Measured: Through study completion, an average of one year
Secondary outcomes (1)
ED50 (post-bronchodilator) dose response curve
Median effective dose
Measured: Through study completion, an average of one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start11 Jan 2019
- Primary completion31 Jan 2020
- Study completion31 Jan 2020
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.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a mechanistic study. The first part of the study (mild allergic asthmatics and healthy controls) is to determine reproducibility of dose responses to mannitol-induced coughs. The second part of the study (mild asthmatics only) is to determine the effect of salbutamol on mannitol-induced coughs. Salbutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Syntara, AllerGen NCE Inc.
- Responsible party
- Sponsor
- Investigators
- Gail Gauvreau, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03620422
- Sponsor's protocol ID
- McMaster-MICC4657
- Acronym
- MICC
- Status last verified
- Mar 2019
- First submitted
- 9 Jul 2018
- Last updated
- 17 Feb 2020
- 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 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma
- ClinicalTrials.gov ID
- NCT03620422
- Acronym / sponsor ID
- MICC / McMaster-MICC4657
- Keywords
- Mannitol, Bronchoconstriction, Airway nerve function, Cough, Diagnostic Test, Osmolarity, Salbutamol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Syntara, AllerGen NCE Inc.
- Study start
- 11 Jan 2019 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Jan 2020 (actual)
- First posted
- 8 Aug 2018 (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 study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing reproducibly in mild allergic asthmatics compared with healthy controls and if salbutamol can affect this. Phase 1 of this study is a reproducibility analysis of cough dose response to mannitol in a cohort of mild allergic asthmatics and healthy controls. Phase 2 is a double-blind, placebo-controlled analysis in mild allergic asthmatics assessing the effects of salbutamol on mannitol induced cough.
Detailed description
The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits will determine eligibility. All eligible subjects will be invited back for a third visit, and only subjects with mild allergic asthma will be invited back for a fourth visit.
Screening Period (Visits 1 and 2) - For All Subjects Eligible subjects will be identified during the initial screening procedures with measures of spirometry, hyperresponsiveness to methacholine, complete history, physical examination, allergen skin test, and mannitol cough challenge. The screening procedures will be conducted over 2 separate visits.
Reproducibility (Visit 3) - For Healthy Controls Ten normal healthy controls meeting study eligibility will return for visit 3. This visit must be at least 24h after the mannitol test at visit 1. These data will be used for assessing reproducibility of the mannitol induced coughs; Emax and the median effective dose (ED50).
Effects of Salbutamol (Visit 3 and 4) - For Mild Allergic Asthma Subjects Ten subjects with mild allergic asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Mild allergic asthmatics will first receive salbutamol 2.5mg or saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the previous mannitol cough challenges. These data will be used for determining the effects of salbutamol on mannitol-induced bronchoconstriction and cough.
Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visits 2 at the same time of day ± 2 hours
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- This is a mechanistic study. The first part of the study (mild allergic asthmatics and healthy controls) is to determine reproducibility of dose responses to mannitol-induced coughs. The second part of the study (mild asthmatics only) is to determine the effect of salbutamol on mannitol-induced coughs. Salbutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Other | Other: MannitolMannitol-Induced Cough Challenges on Visit 2 and 3. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. |
| Mild Allergic Asthmatics (Saline) | Placebo comparator | Other: Mannitol, Other: Sodium Chloride 0.9% Inhl 3MlMannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized placebo (Sodium Chloride 0.9% Inhl 3Ml) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. |
| Mild Allergic Asthmatics (Salbutamol) | Active comparator | Other: Mannitol, Drug: Salbutamol 5mg/mLMannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Able to understand and give written informed consent
- Male and female volunteers 18 through 65 years of age.
- Positive skin-prick test to common aeroallergens (mild allergic asthmatic subjects)
- Asthma as determined by methacholine provocative concentration causing a 20% fall (PC20) ≤16 mg/ml for mild allergic asthmatic subjects; no airway hyperresponsiveness as determined by methacholine PC20>16mg/ml for normal healthy controls.
- Baseline FEV1 ≥ 70% of the predicted value for mild allergic asthmatic subjects; baseline FEV1≥ 80% of the predicted value for normal healthy controls.
Key exclusion criteria (14 listed)
- Current or former smoker with >10-pack-year history
- Current or previous history of other significant respiratory disease
- Significant systemic disease, including history of current malignancy or autoimmune disease
- Asthma exacerbation or upper/lower respiratory tract infection within the previous 8 weeks
- Pregnancy
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 |
|---|---|---|
| MannitolAlso: AridolMannitol-Induced Cough Challenge | Other | Healthy Controls, Mild Allergic Asthmatics (Salbutamol), Mild Allergic Asthmatics (Saline) |
| Salbutamol 5mg/mLAlso: Active ComparatorNebulized salbutamol given prior to Mannitol-Induced Cough Challenge | Drug | Mild Allergic Asthmatics (Salbutamol) |
| Sodium Chloride 0.9% Inhl 3MlAlso: Placebo ComparatorNebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge | Other | Mild Allergic Asthmatics (Saline) |
Primary outcome
ED50 dose response curve
Time frame: Through study completion, an average of one year
Median effective dose
1 secondary outcome
ED50 (post-bronchodilator) dose response curve
Time frame: Through study completion, an average of one year
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 17 Feb 2020.
- 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.
Gail Gauvreau, PhD principal investigator
McMaster 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 Mannitol, Salbutamol 5mg/mL and Sodium Chloride 0.9% Inhl 3Ml in people with Asthma and Cough, run by McMaster 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 6 inclusion and 14 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 17 Feb 2020. 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. Some participants in this study may receive a placebo. 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?
ED50 dose response curve (time frame: Through study completion, an average of one year). 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 17 Feb 2020.