HyperventilationNCT05565430
Vocal Cord Responses During Hyperventilation in Normal Individuals and in Mild and Severe Asthmatics.
An observational study of Hyperventilation and Larynx, run by Monash Medical Centre at 1 site in Australia.
Trial summary
The Investigators aim to: 1. Study the effect of hyperventilation on the development of paradoxical vocal cord movement (PVCM) in healthy individuals and in patients with mild and severe asthma, 2. Relate PVCM to airway symptoms and measurements of intra- and extra-thoracic airway hyperresponsiveness (ET-AHR), 3. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperventilation, Larynx, Asthma
- What is being tested?
- Acute Hyperventilation, Chronic hyperventilation and Effects of anticholinergic medication
- How many people
- 24 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Jun 2018to 10 Feb 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy controls: We shall recruit 8 normal healthy subjects (Group 1). Inclusion criteria for healthy controls include age >18 to 65 years old, non-smokers and no history of chronic respiratory symptoms. Asthmatics: We shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3). Mild asthma will be defined as patients with forced expiratory volume in 1 second (FEV1) >80% predicted. Severe asthma will be defined as patients with FEV1 50-60% predicted. Asthmatics will also have a forced expiratory ratio (FER) less than the lower limit of normal, indicating obstruction.
Who may be able to join
- age >18 to 65 years old
- non-smokers
- No history of chronic respiratory symptoms.
- The Investigators shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3).
- Mild asthma will be defined as patients with forced expiratory volume in 1 second (FEV1) >80% predicted.
- Severe asthma will be defined as patients with FEV1 50-60% predicted.
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- Asthmatics will also have a forced expiratory ratio (FER) less than the lower limit of normal, indicating obstruction.
- age 18-65 years
- A history of asthma defined as a bronchodilator response with increase in FEV1 >12% and 200mls or positive bronchoprovocation testing (methacholine).
- Asthmatics will have FEV1 >50% predicted.
Who cannot join
- Age < 18 or > 65, smokers or smoking history >10 pack years
- Any history of respiratory disorders such as asthma or chronic obstructive pulmonary disease (COPD)
- Known vocal cord pathology (i.e. laryngeal cancer) or diagnosed voice condition
- Known brain or brainstem cancer
- Known head and neck cancer
- Known neurological disorders (i.e. stroke)
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- Use of medications (i.e. beta-blockers or anti-cholinergic agents which may interfere with vocal cord function)
- Singers
- Pregnancy.
- Exclusion criteria will include:
- Age < 18 or > 65
- Smoking history > 10 pack years,
- FEV1 < 50% predicted
- Allergy to anti-cholinergics, known COPD
- Known vocal cord pathology (i.e. laryngeal cancer) or diagnosed voice condition
- Known brain or brainstem cancer
- Known head and neck cancer
- Known neurological disorders (i.e. stroke)
- Singers
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Vocal Cord Responses During Hyperventilation in Normal Individuals and in Mild and Severe
The Investigators aim to:
- Study the effect of hyperventilation on the development of paradoxical vocal cord movement (PVCM) in healthy individuals and in patients with mild and severe asthma,
- Relate PVCM to airway symptoms and measurements of intra- and extra-thoracic airway hyperresponsiveness (ET-AHR),
- Evaluate the effects of inhaled anti-cholinergic agents on PVCM induced by hyperventilation.
Hypotheses:
- In health PVCM will not occur in response to hyperventilation,
- In asthma PVCM will occur in response to hyperventilation,
- Airway symptoms and ET-AHR will develop in parallel with PVCM,
- Inhaled anticholinergic agents will prevent PVCM induced by hyperventilation.
Read the detailed description
Specific aims:
Project 1 - 'Acute' hyperventilation in normal subjects and asthmatics.
Aim 1.1: To measure PVCM by endoscopy in response to a single period of hyperventilation in normal subjects and asthmatics.
Aim 1.2: To relate PVCM to symptoms in both groups. Aim 1.3: To relate PVCM to bronchial and ET-AHR before and after acute hyperventilation.
Project 2 - 'Chronic' hyperventilation and the effect on vocal cord movements in asthmatic subjects.
Aim 2.1: To measure PVCM by endoscopy in response to multiple periods of hyperventilation (twice daily over 2 weeks) in normal subjects and asthmatics.
Aim2.2: To relate PVCM to symptoms in both groups. Aim 2.1: To relate PVCM to bronchial and ET-AHR before and after chronic hyperventilation.
Project 3 (a) - Effects of anticholinergic medication on PVCM.
Aim 3.1: Determine the effect of anti-cholinergic inhaled medications on PVCM induced by hyperventilation.
Project 3 (b) - PVCM during exercise and the effects of anticholinergic medication on PVCM If no PVCM is detected in project 1 and 2, as an alternative strategy the Investigators will examine PVCM that has been shown to occur in severe asthma in response to exercise. The effect of anti-cholinergic inhaled medications will then be examined in this model.
Significance:
Dysfunctional breathing may be a mechanism whereby symptomatic PVCM develops in asthma but not in health. The proposed studies will enhance the Investigators understanding of the role played by dysfunctional breathing in the pathogenesis of this distressing condition and may provide a rationale for targeted therapies.
- Conditions
- Hyperventilation, Larynx, Asthma
- Being tested
- Acute Hyperventilation, Chronic hyperventilation, Effects of anticholinergic medication
- Keywords
- Hyperventilation, Asthma, Vocal Cords, Extra-thoracic airway hyper-responsiveness, Anti-cholinergics
- Medical subject headings
- Hyperventilation, Laryngeal Diseases, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute HyperventilationOther
Also called Acute Hyperventilation in normal subjects and asthmatics
Laryngoscopy to assess vocal cord function during acute hyperventilation in normal subjects and asthmatics.
Chronic hyperventilationOther
Laryngoscopy to assess vocal cord function during acute hyperventilation in normal subjects and asthmatics.
Effects of anticholinergic medicationDrug
Also called Effects of anticholinergic medication on vocal cord movement
Laryngoscopy to assess vocal cord function after administration of anticholinergic medication.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | 1. Acute Hyperventilation and effects on vocal cord movement.
2. Chronic Hyperventilation and effects on vocal cord movement.
3. Effects of anticholinergic medication on paradoxical vocal cord movement. Receives: Other: Acute Hyperventilation; Other: Chronic hyperventilation; Drug: Effects of anticholinergic medication | |
| Mild Asthmatics | 1. Acute Hyperventilation and effects on vocal cord movement.
2. Chronic Hyperventilation and effects on vocal cord movement.
3. Effects of anticholinergic medication on paradoxical vocal cord movement. Receives: Other: Acute Hyperventilation; Other: Chronic hyperventilation; Drug: Effects of anticholinergic medication | |
| Severe Asthmatics | 1. Acute Hyperventilation and effects on vocal cord movement.
2. Chronic Hyperventilation and effects on vocal cord movement.
3. Effects of anticholinergic medication on paradoxical vocal cord movement. Receives: Other: Acute Hyperventilation; Other: Chronic hyperventilation; Drug: Effects of anticholinergic medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vocal cord aperture measured using continuous laryngoscopy after hyperventilation in normal subjects and asthmatics
For each experiment, the subject will sit in a comfortable armchair and breathe though a rubber mouthpiece and turbine pneumotachometer (Oxycon Delta, Jaeger, Wurzburg, Germany). The airflow and volume signals and that from the carbon dioxide (CO2) analyser will be displayed on a monitor and recorded. Subjects will breath through the spirometer during endoscopy to record respiratory phase for later correlation with laryngeal recording.
Laryngeal movement analysis - Image stills will be taken from the continuous laryngoscopy recording, at end inspiration and end expiration. Measurement of narrowing of the laryngeal structures in relative terms during one breathing cycle, which is independent of the distance between the laryngoscope and the glottis.
Measured: 6 years
Secondary outcomes (3)
Lung function indices after hyperventilation in normal and asthmatic patients.
Spirometry indices after hyperventilation. Baseline spirometry will be recorded. Forced vital capacity (FVC) and forced expiratory volume (FEV1) will be calculated. Both are measurements of volume of air expired after maximum inspiration, measured in litres.
Measured: 6 years
Role of the extra-thoracic airway hyper-responsiveness measured using bronchial provocation test to identify asthma like symptoms.
Role of the extra-thoracic airway hyper-responsiveness to asthma like symptoms using Mannitol bronchial provocation testing
Measured: 6 years
Vocal cord changes after anti-cholinergic inhalers and/or exercise.
Vocal cord changes after anti-cholinergic inhalers and/or exercise. Subjects will inhale 4 puffs of ipratropium bromide (20 mcg/actuation inhalation) or placebo using normal tidal breathing. Subjects will then be exercised on an ergometer (Cateye Ergociser) at 75% to 85% of their predicted maximal heart rate (maximal heart rate equals 220 minus subjects age) for 8 minutes while breathing dry air at 10oC. Laryngoscopy will be conducted in situ as detailed in Project 1.
Exercise will be discontinued and PVCM will be assessed. Final lung function testing will be performed to assess the degree of respiratory obstruction produced.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start1 Jun 2018
- Primary completion10 Feb 2025
- Study completion10 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperventilationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monash Medical Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laurence Ruane, Monash Medical Centre
- Investigators
- Laurence Ruane, BSc, Principal investigator, Monash Health and Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05565430
- Sponsor's protocol ID
- 16151A
- Status last verified
- Oct 2024
- First submitted
- 31 May 2016
- Last updated
- 8 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Though publication
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vocal Cord Responses During Hyperventilation in Normal Individuals and in Mild and Severe
- ClinicalTrials.gov ID
- NCT05565430
- Acronym / sponsor ID
- 16151A
- Conditions
- Hyperventilation, Larynx, Asthma
- Keywords
- Hyperventilation, Asthma, Vocal Cords, Extra-thoracic airway hyper-responsiveness, Anti-cholinergics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Monash Medical CentreUniversity, hospital or other
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 10 Feb 2025 (actual)
- Study completion
- 10 Feb 2025 (actual)
- First posted
- 4 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Investigators aim to:
- Study the effect of hyperventilation on the development of paradoxical vocal cord movement (PVCM) in healthy individuals and in patients with mild and severe asthma,
- Relate PVCM to airway symptoms and measurements of intra- and extra-thoracic airway hyperresponsiveness (ET-AHR),
- Evaluate the effects of inhaled anti-cholinergic agents on PVCM induced by hyperventilation.
Hypotheses:
- In health PVCM will not occur in response to hyperventilation,
- In asthma PVCM will occur in response to hyperventilation,
- Airway symptoms and ET-AHR will develop in parallel with PVCM,
- Inhaled anticholinergic agents will prevent PVCM induced by hyperventilation.
Detailed description
Specific aims:
Project 1 - 'Acute' hyperventilation in normal subjects and asthmatics.
Aim 1.1: To measure PVCM by endoscopy in response to a single period of hyperventilation in normal subjects and asthmatics.
Aim 1.2: To relate PVCM to symptoms in both groups. Aim 1.3: To relate PVCM to bronchial and ET-AHR before and after acute hyperventilation.
Project 2 - 'Chronic' hyperventilation and the effect on vocal cord movements in asthmatic subjects.
Aim 2.1: To measure PVCM by endoscopy in response to multiple periods of hyperventilation (twice daily over 2 weeks) in normal subjects and asthmatics.
Aim2.2: To relate PVCM to symptoms in both groups. Aim 2.1: To relate PVCM to bronchial and ET-AHR before and after chronic hyperventilation.
Project 3 (a) - Effects of anticholinergic medication on PVCM.
Aim 3.1: Determine the effect of anti-cholinergic inhaled medications on PVCM induced by hyperventilation.
Project 3 (b) - PVCM during exercise and the effects of anticholinergic medication on PVCM If no PVCM is detected in project 1 and 2, as an alternative strategy the Investigators will examine PVCM that has been shown to occur in severe asthma in response to exercise. The effect of anti-cholinergic inhaled medications will then be examined in this model.
Significance:
Dysfunctional breathing may be a mechanism whereby symptomatic PVCM develops in asthma but not in health. The proposed studies will enhance the Investigators understanding of the role played by dysfunctional breathing in the pathogenesis of this distressing condition and may provide a rationale for targeted therapies.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | – | Other: Acute Hyperventilation, Other: Chronic hyperventilation, Drug: Effects of anticholinergic medication1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement. |
| Mild Asthmatics | – | Other: Acute Hyperventilation, Other: Chronic hyperventilation, Drug: Effects of anticholinergic medication1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement. |
| Severe Asthmatics | – | Other: Acute Hyperventilation, Other: Chronic hyperventilation, Drug: Effects of anticholinergic medication1. Acute Hyperventilation and effects on vocal cord movement. 2. Chronic Hyperventilation and effects on vocal cord movement. 3. Effects of anticholinergic medication on paradoxical vocal cord movement. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy controls: We shall recruit 8 normal healthy subjects (Group 1). Inclusion criteria for healthy controls include age >18 to 65 years old, non-smokers and no history of chronic respiratory symptoms. Asthmatics: We shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3). Mild asthma will be defined as patients with forced expiratory volume in 1 second (FEV1) >80% predicted. Severe asthma will be defined as patients with FEV1 50-60% predicted. Asthmatics will also have a forced expiratory ratio (FER) less than the lower limit of normal, indicating obstruction.
Key inclusion criteria (10 listed)
- The Investigators shall recruit a total of 16 patients with asthma - 8 patients with mild asthma (Group 2) and 8 patients with severe asthma (Group 3).
Key exclusion criteria (20 listed)
- Exclusion criteria will include:
- Age < 18 or > 65
- Smoking history > 10 pack years,
- FEV1 < 50% predicted
- Allergy to anti-cholinergics, known COPD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute HyperventilationAlso: Acute Hyperventilation in normal subjects and asthmaticsLaryngoscopy to assess vocal cord function during acute hyperventilation in normal subjects and asthmatics. | Other | Healthy Control, Mild Asthmatics, Severe Asthmatics |
| Chronic hyperventilationLaryngoscopy to assess vocal cord function during acute hyperventilation in normal subjects and asthmatics. | Other | Healthy Control, Mild Asthmatics, Severe Asthmatics |
| Effects of anticholinergic medicationAlso: Effects of anticholinergic medication on vocal cord movementLaryngoscopy to assess vocal cord function after administration of anticholinergic medication. | Drug | Healthy Control, Mild Asthmatics, Severe Asthmatics |
Primary outcome
Vocal cord aperture measured using continuous laryngoscopy after hyperventilation in normal subjects and asthmatics
Time frame: 6 years
For each experiment, the subject will sit in a comfortable armchair and breathe though a rubber mouthpiece and turbine pneumotachometer (Oxycon Delta, Jaeger, Wurzburg, Germany). The airflow and volume signals and that from the carbon dioxide (CO2) analyser will be displayed on a monitor and recorded. Subjects will breath through the spirometer during endoscopy to record respiratory phase for later correlation with laryngeal recording. Laryngeal movement analysis - Image stills will be taken from the continuous laryngoscopy recording, at end inspiration and end expiration. Measurement of narrowing of the laryngeal structures in relative terms during one breathing cycle, which is independent of the distance between the laryngoscope and the glottis.
3 secondary outcomes
Lung function indices after hyperventilation in normal and asthmatic patients.
Time frame: 6 years
Role of the extra-thoracic airway hyper-responsiveness measured using bronchial provocation test to identify asthma like symptoms.
Time frame: 6 years
Vocal cord changes after anti-cholinergic inhalers and/or exercise.
Time frame: 6 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Individual participant dataSharing planned: Yes. Though publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laurence Ruane, BSc principal investigator
Monash Health and Monash University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperventilation and Larynx, run by Monash Medical Centre at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vocal cord aperture measured using continuous laryngoscopy after hyperventilation in normal subjects and asthmatics (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.