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

Primary Purpose

Cough

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Salbutamol 5mg/mL

Sodium Chloride 0.9% Inhl 3Ml

About this trial

This is an interventional other trial for Cough

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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
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

Sites / Locations

McMaster Cardio-Respiratory Research Lab
McMaster University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Healthy Control - Active Arm

Healthy control - Placebo Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Primary Outcome - Emax

The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.

Secondary Outcome Measures

Cough dose response curves

Comparison of mannitol-induced cough dose response curves in normal healthy controls treated with salbutamol compared with placebo.

ED50

The effect of salbutamol on mannitol induced coughs E50 - the dose of mannitol causing half the maximal response.

Comparison of the mannitol dose causing 2 coughs (C2) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

Comparison of the mannitol dose causing 5 coughs (C5) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

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.

Full Information

NCT ID

NCT04565847

First Posted

August 17, 2020

Last Updated

June 13, 2022

Sponsor

McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT04565847

Brief Title

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

Acronym

COMA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

November 30, 2020 (Actual)

Primary Completion Date

December 16, 2021 (Actual)

Study Completion Date

December 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

McMaster University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cough

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

albutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy Control - Active Arm

Arm Type

Active Comparator

Arm Description

Arm Title

Healthy control - Placebo Arm

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Salbutamol 5mg/mL

Other Intervention Name(s)

Ventolin nebuliser

Intervention Description

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Intervention Type

Drug

Intervention Name(s)

Sodium Chloride 0.9% Inhl 3Ml

Other Intervention Name(s)

Placebo Comparator

Intervention Description

Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge

Primary Outcome Measure Information:

Title

Primary Outcome - Emax

Description

The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.

Time Frame

Through study completion, an average of 1 year

Secondary Outcome Measure Information:

Title

Cough dose response curves

Description

Comparison of mannitol-induced cough dose response curves in normal healthy controls treated with salbutamol compared with placebo.

Time Frame

Through study completion, an average of 1 year

Title

ED50

Description

The effect of salbutamol on mannitol induced coughs E50 - the dose of mannitol causing half the maximal response.

Time Frame

Through study completion, an average of 1 year

Title

Description

Comparison of the mannitol dose causing 2 coughs (C2) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

Time Frame

Through study completion, an average of 1 year

Title

Description

Comparison of the mannitol dose causing 5 coughs (C5) in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

Time Frame

Through study completion, an average of 1 year

Title

Cumulative number of coughs

Description

Comparison of the cumulative number of coughs in a mannitol induced cough challenge in healthy controls treated with salbutamol compared with placebo.

Time Frame

Through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gail Gauvreau, PhD

Organizational Affiliation

McMaster University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

McMaster Cardio-Respiratory Research Lab

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 3Z5

Country

Canada

Facility Name

McMaster University

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 3Z5

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

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

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