Back to resultsSensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline
Primary Purpose
Asthma, Cough, Cough Variant Asthma
Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Methacholine (MCh) Challenge Testing
Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
Sponsored by
About this trial
This is an interventional basic science trial for Asthma focused on measuring Asthma, Cough, Eucapneic Voluntary Hyperventilation, Hypertonic Saline
Eligibility Criteria
Inclusion Criteria:
Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
- CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
- Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).
- Individuals aged 18-65 years of age with no history of asthma or chronic cough.
Exclusion Criteria:
- an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
- inability to perform acceptable spirometry
- medical contraindications to methacholine challenge testing
- smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.
Sites / Locations
- Kingston Health Sciences CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cough Variant Asthma
Methacholine-induced cough
Control
Arm Description
Individuals diagnosed with Cough variant asthma
Individuals with chronic cough and negative methacholine challenge
Individuals with no history of asthma or chronic cough
Outcomes
Primary Outcome Measures
Mid expiratory flows
The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.
Secondary Outcome Measures
Respiratory System Reactance (X5)
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Peripheral Resistance (R5-R20)
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Central Airway Resistance
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Forced Vital Capacity (FVC)
As an index of airway closure.
FEV1/FVC
As an index of airway obstruction.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03105843
Brief Title
Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline
Official Title
Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline in Individuals With Cough Variant Asthma and Chronic Cough
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Diane Lougheed
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough.
We hypothesize:
EVH and HS cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls.
The sensory-mechanical responses to both hyperosmolar challenges (EVH and HS) are comparable within groups (CVA, COUGH and healthy controls).
Detailed Description
Asthma is a chronic respiratory condition characterized by eosinophilic airway inflammation. Individuals with classic asthma experience paroxysmal symptoms including cough, wheeze, shortness of breath and chest tightness. Cough variant asthma (CVA) is asthma in which chronic cough (cough lasting eight weeks or more) is the sole or predominant symptom of asthma. The pathophysiologic mechanisms which differentiate asthma, CVA, and eosinophilic bronchitis without asthma are not fully understood. We have recently identified individuals with chronic cough who cough during methacholine but have normal airway sensitivity (ie. do not have asthma or CVA) (COUGH) and may or may not have eosinophilic bronchitis. The purpose of this research is to further explore the pathophysiologic basis for cough in these conditions using two 'indirect' inhalation challenge tests: eucapneic voluntary hyperventilation (EVH) and hypertonic saline (HS), which induce osmotic and/or temperature changes in airway. Specifically, this study will collect preliminary data on the sensory-mechanical responses of individuals with CVA, COUGH and healthy controls to EVH and HS challenge.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Cough, Cough Variant Asthma
Keywords
Asthma, Cough, Eucapneic Voluntary Hyperventilation, Hypertonic Saline
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cough Variant Asthma
Arm Type
Experimental
Arm Description
Individuals diagnosed with Cough variant asthma
Arm Title
Methacholine-induced cough
Arm Type
Experimental
Arm Description
Individuals with chronic cough and negative methacholine challenge
Arm Title
Control
Arm Type
Experimental
Arm Description
Individuals with no history of asthma or chronic cough
Intervention Type
Drug
Intervention Name(s)
Methacholine (MCh) Challenge Testing
Other Intervention Name(s)
MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)], Provocholine
Intervention Description
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Intervention Type
Diagnostic Test
Intervention Name(s)
Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
Intervention Description
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Primary Outcome Measure Information:
Title
Mid expiratory flows
Description
The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.
Time Frame
Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test
Secondary Outcome Measure Information:
Title
Respiratory System Reactance (X5)
Description
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Time Frame
After dose administration; will occur 2-5 minutes after dose
Title
Peripheral Resistance (R5-R20)
Description
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Time Frame
After dose administration; will occur 2-5 minutes after dose
Title
Central Airway Resistance
Description
Single IOS will measure peripheral airway function using respiratory system reactance (X5) and peripheral resistance (R5-R20) and central resistance (R20) will be used as an index of airway narrowing.
Time Frame
After dose administration; will occur 2-5 minutes after dose
Title
Forced Vital Capacity (FVC)
Description
As an index of airway closure.
Time Frame
After dose administration; will occur 2-5 minutes after dose
Title
FEV1/FVC
Description
As an index of airway obstruction.
Time Frame
After dose administration; will occur 2-5 minutes after dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).
Individuals aged 18-65 years of age with no history of asthma or chronic cough.
Exclusion Criteria:
an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
inability to perform acceptable spirometry
medical contraindications to methacholine challenge testing
smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
M. Diane Lougheed, MD, MSc
Phone
613-548-2348
Email
diane.lougheed@kingstonhsc.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Taylar Wall, RRT
Phone
613-549-6666
Ext
2798
Email
taylar.wall@kingstonhsc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M. Diane Lougheed, MD, MSc
Organizational Affiliation
Department of Medicine, Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kingston Health Sciences Centre
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taylor Wall
Phone
613-549-6666
Ext
2798
Email
taylor.wall@kingstonhsc.ca
First Name & Middle Initial & Last Name & Degree
M Diane Lougheed, MD MSc
12. IPD Sharing Statement
Plan to Share IPD
No
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Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline
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