The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls (COMA)

• ClinicalTrials.gov Identifier: NCT04565847
• Recruitment Status: Not yet recruiting
• First Posted: September 25, 2020
• Last Update Posted: September 25, 2020
• Sponsor: McMaster University
• Information provided by (Responsible Party): Gail Gauvreau, McMaster University

Study Description

Brief 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. This is a double-blind, placebo-controlled analysis in healthy controls assessing the effects of salbutamol on mannitol induced cough.

Condition or disease	Intervention/treatment	Phase
Cough	Drug: Salbutamol 5mg/mL; Drug: Sodium Chloride 0.9% Inhl 3Ml	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: albutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls
• Estimated Study Start Date: September 15, 2020
• Estimated Primary Completion Date: September 30, 2021
• Estimated Study Completion Date: September 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Healthy Control - Active Arm; 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.	Drug: Salbutamol 5mg/mL; Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge; Other Name: Ventolin nebuliser
Placebo Comparator: Healthy control - Placebo Arm; 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.	Drug: Sodium Chloride 0.9% Inhl 3Ml; Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge; Other Name: Placebo Comparator

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. Cough dose response curves [ Time Frame: Through study completion, an average of 1 year ]
   Comparison of mannitol-induced cough dose response curves in normal healthy controls treated with salbutamol compared with placebo.
2. ED50 [ Time Frame: Through study completion, an average of 1 year ]
   The effect of salbutamol on mannitol induced coughs E50 - the dose of mannitol causing half the maximal response.
3. C2 [ Time Frame: Through study completion, an average of 1 year ]
   Comparison of the mannitol dose causing 2 coughs (C2) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.
4. C5 [ Time Frame: Through study completion, an average of 1 year ]
   Comparison of the mannitol dose causing 5 coughs (C5) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.
5. Cumulative number of coughs [ Time Frame: Through study completion, an average of 1 year ]
   Comparison of the cumulative number of coughs in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Able to understand and give written informed consent.
2. Male and female volunteers 18 through 65 years of age.
3. 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.
4. 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).
5. Baseline FEV1≥ 80% of the predicted value.
6. Demonstrate cough response to inhaled mannitol.

Exclusion Criteria:

1. Current or former smoker with >10-pack-year history
2. Current or previous history of other significant respiratory disease
3. Significant systemic disease, including history of current malignancy or autoimmune disease
4. Pregnancy or breastfeeding.
5. Use of corticosteroids within 28 days prior to the first study visit.
6. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
7. Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
8. Use of caffeine-containing products within 4 hours of study visits
9. Use of ACE inhibitors
10. 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.
11. Unwillingness or inability to comply with the study protocol for any other reason

Contacts and Locations

Contacts

Contact: Gail Gauvreau, PhD; 9055259140 ext 22791; gauvreau@mcmaster.ca

Locations

Canada, Ontario

McMaster Cardio-Respiratory Research Lab

Hamilton, Ontario, Canada, L8N 3Z5

McMaster University

Hamilton, Ontario, Canada, L8N 3Z5

Sponsors and Collaborators

McMaster University

Investigators

• Principal Investigator: Gail Gauvreau, PhD; McMaster University Hospital

More Information

• Responsible Party: Gail Gauvreau, Professor Department of MEdicine, McMaster University
• ClinicalTrials.gov Identifier: NCT04565847
• Other Study ID Numbers: McMaster-COMA-11537
• First Posted: September 25, 2020
• Last Update Posted: September 25, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action