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Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests

Primary Purpose

Asthma, Cough Variant Asthma

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
high-dose methacholine challenge test
mannitol challenge test
Sponsored by
Dr. Diane Lougheed
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Asthma focused on measuring Asthma, Cough Variant Asthma, Mannitol, Methacholine, Cough, Hypersensitivity

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects with asthma or suspected CVA who have previously participated in or who have expressed interest in participating in studies will be invited to participate in the study. Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion, but medication use will be recorded and examined in the analysis.

Exclusion Criteria:

  1. An exacerbation necessitating any alteration in medication, emergency department visit or hospitalizations within the previous 4 weeks;
  2. Inability to perform acceptable quality spirometry;
  3. Medical contraindications to methacholine challenge testing 35, including:

    1. Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
    2. Heart attack or stroke in last 3 months;
    3. Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
    4. Known aortic aneurysm;
    5. Moderate airflow limitation < 60% predicted or <1.5 L);
    6. Inability to perform acceptable quality spirometry;
    7. Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
    8. Pregnant or nursing mothers.
  4. Smoking history in excess of 10 pack years;
  5. Medical contraindications to mannitol challenge testing, including:

    1. Aortic or cerebral aneurysm;
    2. Uncontrolled hypertension; and
    3. Myocardial infarction or a cerebral vascular accident in the previous six months).
  6. Women who are pregnant or breastfeeding because the effects of a possible hyperresponsiveness reaction to mannitol in mothers and/or fetuses are unknown and many compounds are excreted in human milk therefore caution should be taken.

Sites / Locations

  • Kingston General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cough Variant Asthma

Asthma

Arm Description

Those diagnosed with cough variant asthma.

Those with diagnosed asthma.

Outcomes

Primary Outcome Measures

PD15 (15% fall in forced expiratory volume in one second (FEV1) from baseline during challenge test visits)

Secondary Outcome Measures

%ΔFEV1 (percentage change in forced expiratory volume in one second)
Plateau response
Dose-response slope
Expiratory Flow Limitation (EFL)

Full Information

First Posted
February 1, 2010
Last Updated
February 9, 2022
Sponsor
Dr. Diane Lougheed
Collaborators
The Ontario Thoracic Society of the Ontario Lung Association, Queen's University (William M Spear / Start Memorial Fund)
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1. Study Identification

Unique Protocol Identification Number
NCT01064245
Brief Title
Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests
Official Title
Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2010 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Diane Lougheed
Collaborators
The Ontario Thoracic Society of the Ontario Lung Association, Queen's University (William M Spear / Start Memorial Fund)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Cough is a common, disruptive and at times disabling symptom which often prompts patients to seek medical attention. Determining the cause(s) of chronic cough can be challenging, and costly. Asthma and other airway disorders are among the most common causes of chronic cough; and cough can be the sole symptom of asthma. Little is known about why some patients with asthma primarily cough and do not develop the other symptoms of asthma such as shortness of breath or wheeze. Improved understanding of the reasons for these different manifestations may lead to new and more effective treatment strategies. We have notices differences in pressure measurements inside the chest in patients who mostly cough during induced bronchoconstriction, which might be part of the explanation for varying symptoms. This study will compare lung mechanical responses during methacholine and mannitol-induced induced airway narrowing between typical asthma, cough variant asthma (CVA) and an airway inflammatory disorder that is not asthma.The purpose of this research is to explore the pathophysiology and sensory-mechanics of cough in individuals with asthma, CVA and methacholine-induced cough but normal airway sensitivity using mannitol and high-dose methacholine bronchoprovocation testing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Cough Variant Asthma
Keywords
Asthma, Cough Variant Asthma, Mannitol, Methacholine, Cough, Hypersensitivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cough Variant Asthma
Arm Type
Experimental
Arm Description
Those diagnosed with cough variant asthma.
Arm Title
Asthma
Arm Type
Experimental
Arm Description
Those with diagnosed asthma.
Intervention Type
Drug
Intervention Name(s)
high-dose methacholine challenge test
Other Intervention Name(s)
Provocholine
Intervention Description
nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses
Intervention Type
Other
Intervention Name(s)
mannitol challenge test
Other Intervention Name(s)
Aridol
Intervention Description
inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg
Primary Outcome Measure Information:
Title
PD15 (15% fall in forced expiratory volume in one second (FEV1) from baseline during challenge test visits)
Time Frame
baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test)
Secondary Outcome Measure Information:
Title
%ΔFEV1 (percentage change in forced expiratory volume in one second)
Time Frame
baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test)
Title
Plateau response
Time Frame
baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test)
Title
Dose-response slope
Time Frame
baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test)
Title
Expiratory Flow Limitation (EFL)
Time Frame
baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with asthma or suspected CVA who have previously participated in or who have expressed interest in participating in studies will be invited to participate in the study. Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion, but medication use will be recorded and examined in the analysis. Exclusion Criteria: An exacerbation necessitating any alteration in medication, emergency department visit or hospitalizations within the previous 4 weeks; Inability to perform acceptable quality spirometry; Medical contraindications to methacholine challenge testing 35, including: Severe airflow limitation (FEV1 <50% predicted or <1.0 L); Heart attack or stroke in last 3 months; Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100; Known aortic aneurysm; Moderate airflow limitation < 60% predicted or <1.5 L); Inability to perform acceptable quality spirometry; Current use of cholinesterase inhibitor medication (for myasthenia gravis); and Pregnant or nursing mothers. Smoking history in excess of 10 pack years; Medical contraindications to mannitol challenge testing, including: Aortic or cerebral aneurysm; Uncontrolled hypertension; and Myocardial infarction or a cerebral vascular accident in the previous six months). Women who are pregnant or breastfeeding because the effects of a possible hyperresponsiveness reaction to mannitol in mothers and/or fetuses are unknown and many compounds are excreted in human milk therefore caution should be taken.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diane Lougheed, MD
Organizational Affiliation
Queen's University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Scott Turcotte
Organizational Affiliation
Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L2V7
Country
Canada

12. IPD Sharing Statement

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Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests

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