CoughPhase 2COMANCT04565847
The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls
A Phase 2 study testing Salbutamol 5mg/mL and Sodium Chloride 0.9% Inhl 3Ml in people with Cough, run by McMaster University at 2 sites in Canada.
Trial summary
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing healthy controls with no evidence of bronchoconstriction (PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cough
- What is being tested?
- 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
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- 30 Nov 2020to 16 Dec 2021
- Phase
- Phase 2
- 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.
- No airway hyperresponsiveness as determined by methacholine PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses.
- Fall in FEV1 of ≤ 5% after any mannitol dose during mannitol challenge compared to baseline FEV1 at 0 mg at screening mannitol challenge (Visit 2).
- Baseline FEV1≥ 80% of the predicted value.
- 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
- Pregnancy or breastfeeding.
- Use of corticosteroids within 28 days prior to the first study visit.
- Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
Show all 11Show fewer
- Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
- Use of caffeine-containing products within 4 hours of study visits
- Use of 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.
- Unwillingness or inability to comply with the study protocol for any other reason
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
McMaster Cardio-Respiratory Research Lab
Hamilton, Ontario, L8N 3Z5
McMaster University
Hamilton, Ontario, L8N 3Z5
About this study
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing healthy controls with no evidence of bronchoconstriction (PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. This is a double-blind, placebo-controlled analysis in healthy controls 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 and 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.
Effects of Salbutamol (Visit 3 and 4) - For Healthy Control Subjects, Twenty subjects with no evidence of asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Health controls 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 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
- Conditions
- Cough
- Being tested
- Salbutamol 5mg/mL, Sodium Chloride 0.9% Inhl 3Ml
- Medical subject headings
- Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salbutamol 5mg/mLDrug
Also called Ventolin nebuliser
Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge
Sodium Chloride 0.9% Inhl 3MlDrug
Also called Placebo Comparator
Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control - Active Arm | Active comparator | Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Receives: Drug: Salbutamol 5mg/mL |
| Healthy control - Placebo Arm | Placebo comparator | Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized 0.9% Saline given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Receives: Drug: Sodium Chloride 0.9% Inhl 3Ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome - Emax
The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.
Measured: Through study completion, an average of 1 year
Secondary outcomes (5)
Cough dose response curves
Comparison of mannitol-induced cough dose response curves in normal healthy controls treated with salbutamol compared with placebo.
Measured: Through study completion, an average of 1 year
ED50
The effect of salbutamol on mannitol induced coughs E50 - the dose of mannitol causing half the maximal response.
Measured: Through study completion, an average of 1 year
C2
Comparison of the mannitol dose causing 2 coughs (C2) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.
Measured: Through study completion, an average of 1 year
C5
Comparison of the mannitol dose causing 5 coughs (C5) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.
Measured: Through study completion, an average of 1 year
Cumulative number of coughs
Comparison of the cumulative number of coughs in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start30 Nov 2020
- Primary completion16 Dec 2021
- Study completion16 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CoughStudies 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- albutamol 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gail Gauvreau, McMaster University
- Investigators
- Gail Gauvreau, PhD, Principal investigator, McMaster University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565847
- Sponsor's protocol ID
- McMaster-COMA-11537
- Acronym
- COMA
- Status last verified
- Jun 2022
- First submitted
- 17 Aug 2020
- Last updated
- 16 Jun 2022
- 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 16 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls
- ClinicalTrials.gov ID
- NCT04565847
- Acronym / sponsor ID
- COMA / McMaster-COMA-11537
- Conditions
- Cough
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 16 Dec 2021 (actual)
- Study completion
- 16 Dec 2021 (actual)
- First posted
- 25 Sep 2020 (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 healthy controls with no evidence of bronchoconstriction (PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. This is a double-blind, placebo-controlled analysis in healthy controls 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 and 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.
Effects of Salbutamol (Visit 3 and 4) - For Healthy Control Subjects, Twenty subjects with no evidence of asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Health controls 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 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
- 2
- Model description
- albutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
| Arm | Type | Receives |
|---|---|---|
| Healthy Control - Active Arm | Active comparator | Drug: Salbutamol 5mg/mLHealthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. |
| Healthy control - Placebo Arm | Placebo comparator | Drug: Sodium Chloride 0.9% Inhl 3MlHealthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized 0.9% Saline given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. |
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.
- No airway hyperresponsiveness as determined by methacholine PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses.
- Fall in FEV1 of ≤ 5% after any mannitol dose during mannitol challenge compared to baseline FEV1 at 0 mg at screening mannitol challenge (Visit 2).
- Baseline FEV1≥ 80% of the predicted value.
Key exclusion criteria (11 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
- Pregnancy or breastfeeding.
- Use of corticosteroids within 28 days prior to the first study visit.
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 |
|---|---|---|
| Salbutamol 5mg/mLAlso: Ventolin nebuliserNebulized salbutamol given prior to Mannitol-Induced Cough Challenge | Drug | Healthy Control - Active Arm |
| Sodium Chloride 0.9% Inhl 3MlAlso: Placebo ComparatorNebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge | Drug | Healthy control - Placebo Arm |
Primary outcome
Primary Outcome - Emax
Time frame: Through study completion, an average of 1 year
The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.
5 secondary outcomes
Cough dose response curves
Time frame: Through study completion, an average of 1 year
ED50
Time frame: Through study completion, an average of 1 year
C2
Time frame: Through study completion, an average of 1 year
C5
Time frame: Through study completion, an average of 1 year
Cumulative number of coughs
Time frame: Through study completion, an average of 1 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 16 Jun 2022.
- Individual participant dataSharing planned: No
Related trials for Cough
RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
RecruitingObservational study
Physical Impairments in Premature Ventricular Complex
Premature Ventricular Complexes
RecruitingObservational study
Office-Based Superior Laryngeal Nerve Block for Treatment of Neurogenic Cough
Cough
Not yet recruiting
High-Flow Nasal Oxygen-Assisted Deep Extubation Versus Awake Extubation in Morbidly Obese Patients
Deep Tracheal Extubation
Recruiting
Feasibility of Cough Skill Training in Individuals With Head and Neck Cancer
Head and Neck Cancers
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 Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Salbutamol 5mg/mL and Sodium Chloride 0.9% Inhl 3Ml in people with Cough, run by McMaster University at 2 sites 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 11 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 16 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Primary Outcome - Emax (time frame: Through study completion, an average of 1 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 16 Jun 2022.