Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol

March 17, 2025 updated by: Dr. Diane Lougheed

Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol in Individuals with Cough Variant Asthma and Chronic Cough

The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol 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 Mannitol 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 Mannitol) are comparable within groups (CVA, COUGH and healthy controls).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Mannitol), 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 Mannitol Challenges.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Recruiting
        • Kingston Health Sciences Centre
        • Contact:
        • Contact:
          • M Diane Lougheed, MD MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • Provocholine
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
Diagnostic test: Eucapneic Voluntary Hyperventilation (EVH)
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Drug: Mannitol Inhalation Kit
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Other Names:
  • Mannitol Challenge Test
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:
  • Provocholine
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
Diagnostic test: Eucapneic Voluntary Hyperventilation (EVH)
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Drug: Mannitol Inhalation Kit
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Other Names:
  • Mannitol Challenge Test
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:
  • Provocholine
  • MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)]
Diagnostic test: Eucapneic Voluntary Hyperventilation (EVH)
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Drug: Mannitol Inhalation Kit
Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
Other Names:
  • Mannitol Challenge Test

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
After dose administration; will occur 2-5 minutes after dose
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.
After dose administration; will occur 2-5 minutes after dose
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.
After dose administration; will occur 2-5 minutes after dose
Forced Vital Capacity (FVC)
Time Frame: After dose administration; will occur 2-5 minutes after dose
As an index of airway closure.
After dose administration; will occur 2-5 minutes after dose
FEV1/FVC
Time Frame: After dose administration; will occur 2-5 minutes after dose
As an index of airway obstruction.
After dose administration; will occur 2-5 minutes after dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dr. Diane Lougheed

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: M. Diane Lougheed, MD, MSc, Department of Medicine, Queen's University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 10, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2023-17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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