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Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline

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ClinicalTrials.gov Identifier: NCT03105843
Recruitment Status : Not yet recruiting
First Posted : April 10, 2017
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Diane Lougheed, Queen's University

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:

  1. 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.
  2. The sensory-mechanical responses to both hyperosmolar challenges (EVH and HS) are comparable within groups (CVA, COUGH and healthy controls).

Condition or disease Intervention/treatment Phase
Asthma Cough Cough Variant Asthma Drug: Methacholine (MCh) Challenge Testing Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Hypertonic Saline in Individuals With Cough Variant Asthma and Chronic Cough
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : July 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Cough

Arm Intervention/treatment
Experimental: Cough Variant Asthma
Individuals diagnosed with Cough variant asthma
Drug: Methacholine (MCh) Challenge Testing
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Other Names:
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
  • Provocholine

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.

Experimental: Methacholine-induced cough
Individuals with chronic cough and negative methacholine challenge
Drug: Methacholine (MCh) Challenge Testing
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Other Names:
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
  • Provocholine

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.

Experimental: Control
Individuals with no history of asthma or chronic cough
Drug: Methacholine (MCh) Challenge Testing
Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
Other Names:
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
  • Provocholine

Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
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 Measures :
  1. Mid expiratory flows [ 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 ]
    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 :
  1. Respiratory System Reactance (X5) [ Time Frame: After dose administration; will occur 2-5 minutes after dose ]
    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.

  2. Peripheral Resistance (R5-R20) [ Time Frame: After dose administration; will occur 2-5 minutes after dose ]
    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.

  3. Central Airway Resistance [ Time Frame: After dose administration; will occur 2-5 minutes after dose ]
    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.

  4. Forced Vital Capacity (FVC) [ Time Frame: After dose administration; will occur 2-5 minutes after dose ]
    As an index of airway closure.

  5. FEV1/FVC [ Time Frame: After dose administration; will occur 2-5 minutes after dose ]
    As an index of airway obstruction.



Information from the National Library of Medicine

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

    1. 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);
    2. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03105843


Contacts
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Contact: M. Diane Lougheed, MD, MSc 613-548-2348 lougheed@kgh.kari.net
Contact: Taylar Wall, RRT 613-549-6666 ext 2798 wallt@KGH.KARI.NET

Locations
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Canada, Ontario
Kingston Health Sciences Centre Not yet recruiting
Kingston, Ontario, Canada, K7L 2V7
Principal Investigator: M Diane Lougheed, MD MSc         
Sponsors and Collaborators
Queen's University
Investigators
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Principal Investigator: M. Diane Lougheed, MD, MSc Department of Medicine, Queen's University

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Responsible Party: Dr. Diane Lougheed, Professor of Medicine, Queen's University
ClinicalTrials.gov Identifier: NCT03105843     History of Changes
Other Study ID Numbers: 2023-17
First Posted: April 10, 2017    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Dr. Diane Lougheed, Queen's University:
Asthma
Cough
Eucapneic Voluntary Hyperventilation
Hypertonic Saline

Additional relevant MeSH terms:
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Asthma
Lung Diseases, Obstructive
Lung Diseases
Cough
Hyperventilation
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Methacholine Chloride
Miotics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Parasympathomimetics
Bronchoconstrictor Agents
Respiratory System Agents
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action