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Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma (MICC)

Primary Purpose

Asthma, Cough

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Mannitol

Salbutamol 5mg/mL

Sodium Chloride 0.9% Inhl 3Ml

About this trial

This is an interventional other trial for Asthma focused on measuring Mannitol, Bronchoconstriction, Airway nerve function, Cough, Diagnostic Test, Osmolarity, Salbutamol

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.
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

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
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.
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.

Sites / Locations

McMaster University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Placebo Comparator

Active Comparator

Arm Label

Healthy Controls

Mild Allergic Asthmatics (Saline)

Mild Allergic Asthmatics (Salbutamol)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

ED50 dose response curve

Median effective dose

Secondary Outcome Measures

ED50 (post-bronchodilator) dose response curve

Median effective dose

Full Information

NCT ID

NCT03620422

First Posted

July 9, 2018

Last Updated

February 12, 2020

Sponsor

McMaster University

Collaborators

Pharmaxis, AllerGen NCE Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03620422

Brief Title

Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma

Acronym

MICC

Official Title

Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

January 11, 2019 (Actual)

Primary Completion Date

January 31, 2020 (Actual)

Study Completion Date

January 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

McMaster University

Collaborators

Pharmaxis, AllerGen NCE Inc.

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 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

6. Conditions and Keywords

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

Asthma, Cough

Keywords

Mannitol, Bronchoconstriction, Airway nerve function, Cough, Diagnostic Test, Osmolarity, Salbutamol

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy Controls

Arm Type

Other

Arm Description

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.

Arm Title

Mild Allergic Asthmatics (Saline)

Arm Type

Placebo Comparator

Arm Description

Arm Title

Mild Allergic Asthmatics (Salbutamol)

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Mannitol

Other Intervention Name(s)

Aridol

Intervention Description

Mannitol-Induced Cough Challenge

Intervention Type

Drug

Intervention Name(s)

Salbutamol 5mg/mL

Other Intervention Name(s)

Active Comparator

Intervention Description

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Intervention Type

Other

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

ED50 dose response curve

Description

Median effective dose

Time Frame

Through study completion, an average of one year

Secondary Outcome Measure Information:

Title

ED50 (post-bronchodilator) dose response curve

Description

Median effective dose

Time Frame

Through study completion, an average of one 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. 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 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 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gail Gauvreau, PhD

Organizational Affiliation

McMaster University

Official's Role

Principal Investigator

Facility Information:

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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Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma

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