Healthy VolunteersNCT03902639
Examining the Effects of Nasal High Flow Oxygen Therapy Compared to Non-invasive Ventilation in Health Volunteers
An observational study of Healthy Volunteers, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Respiratory failure is characterized by low levels of oxygen and high levels of carbon dioxide in the blood which causes difficulty breathing. The management of patients with respiratory failure aims at improving oxygenation and changing the effort required to breathe. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Phase 1 and 2 and Phase 3
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 10 Apr 2019to 1 Oct 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy volunteers responding to advertisement posted through the St. Michael's Hospital Communications board.
Who may be able to join
- Healthy volunteers ≥ 18 y-o,
- No evidence of acute or chronic cardiopulmonary disease
Who cannot join
- Active epistaxis, sinus problem, nasal trauma, or deviated septum that would preclude the nasopharyngeal catheter insertion,
- Pregnancy, clinical evidence of respiratory illness, history of respiratory disease, body mass of over 50 kg/m2, ribcage malformation,
- Cardiac pace maker or implantable cardioverter-defibrillator according to EIT manufacturer,
- Allergy to topical lidocaine,
- Claustrophobia that would preclude the use of CPAP or HFNC.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparative Study of the Physiological Effects of High Flow Nasal Cannula and Non-invasive Ventilation in Healthy Volunteers
Respiratory failure is characterized by low levels of oxygen and high levels of carbon dioxide in the blood which causes difficulty breathing. The management of patients with respiratory failure aims at improving oxygenation and changing the effort required to breathe. Mechanical ventilation is a life-saving treatment but may be associated with a high mortality rate, prolonged stay in the intensive care unit (ICU), and infection. Oxygenation techniques to avoid mechanical ventilation include standard oxygen therapy, continuous positive pressure (CPAP), and high-flow nasal cannula oxygen therapy (HFNC). CPAP consists of delivering oxygen through a mask. As compared to standard oxygen therapy, CPAP can promote lung recruitment leading to improved oxygenation and the effect in work of breathing in patients with respiratory failure. Conversely, high-flow nasal cannula oxygen therapy (HFNC) delivers oxygen through nasal prongs. Oxygen is heated and humidified and can be delivered at different flows (from 10 - 60 L/min). As compared to standard oxygen therapy, HFNC can promote some lung recruitment leading to mofiy oxygenation and work of breathing. Therefore, the present study will have 2 phases:
Phase 1:Comparison of the physiological effects of different flows of HFNC to CPAP in healthy volunteers. The investigators hypothesized that the physiological effects of HFNC in the nasopharynx are comparable to that of CPAP at 4 cm H2O.
Phase 2: Comparison of the physiological effects of different nasal interfaces of HFNC (Standard cannula vs. Asymmetrical cannula vs. Single-nostril adapted cannula) in healthy volunteers. The investigators hypothesized that the physiological effects of HFNC in the nasopharynx are comparable to that of CPAP at 4 cm H2O. It was hypothesized that asymmetrical which is the cannula that has a higher cross-sectional area generates higher nasal pharyngeal pressure.
- Conditions
- Healthy Volunteers
- Being tested
- Phase 1 and 2, Phase 3
- Keywords
- High flow nasal cannula, Airway pressure, Lung volume, Non-invasive ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase 1 and 2Other
First, participant will be randomized to a protocol during our study. Participant will breathe normally at different flows of HFNC (20, 40 or 60 L/min) with their mouth open and mouth closed at each flow. They will breathe normally with CPAP at a positive pressure of 4 cm H2O. A lubricated catheter is inserted above the glottis through the nostril to measure ventilatory parameters. EIT is applied to measure inflation of the lung using electromagnetic waves that are not perceptible and are harmless. An ultrasound is done to measure the thickening of your diaphragm and of your abdominal muscles during inspiration and expiration and vocal cords position with and without HFNC (single measurement - around 3 min).During the second step, second catheter is inserted through the nostril to measure esophageal pressure. They will breathe for one additional minute during the closed mouth portions of the experiment while watching the esophageal pressure to ensure steady effort.
Phase 3Other
In the 3rd phase, according to randomization, volunteers will be masked with either RT041, RT043 or ONIV117 first, followed by the second mask then third mask, also randomize mouth position set to open or closed. The fitting of the masks will be determined based on the manufacturer guidelines and healthy volunteer tolerance. The mask will be adjusted to minimize leaks. At each step, EIT measurements will be recorded at regular breathing over a 10-minute period with an 8-minute washout between devices and 5-minute washout period between mouth positions. The transcutaneous CO2 will be continuously monitored from the earlobe throughout the protocol.
What is being measured
The primary outcome is the main question the study is designed to answer.
End expiratory nasopharyngeal pressure (NP)
The primary endpoint is to compare the end expiratory nasopharyngeal pressure (NP) under 60 L/min of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP 4 cmH2O).This will be assessed using a nasopharyngeal catheter.
Measured: 5 minutes
End expiratory nasopharyngeal pressure (NP)
The primary endpoint is to compare the end expiratory nasopharyngeal pressure (NP) of high flow nasal cannula (HFNC) among the 3 different nasal cannulas (Symmetrical, Asymmetrical, Single-nostril adapted).
Measured: 5min
Secondary outcomes (3)
Change in physiologic variables of airway pressure at different flows of HFNC (20, 40, and 60 L/min) and CPAP (4 cmH20). In the phase#2; HFNC 2, and 50 L/min.
One of the secondary endpoints is to compare variables of airway pressure at different flows of HFNC to CPAP. The investigators will measure the end expiratory NP, mean NP, mean peak inspiratory pressure, mean peak expiratory pressure, delta inspiratory pressure and delta expiratory pressure.
Each of these variables will be measured for 1 minute using a nasopharyngeal catheter. Furthermore, at each flow of HFNC, the investigators will ask the patient to breathe with their mouth open and mouth closed.
Measured: 5 minutes
Change in end-expiratory lung impedance
The other secondary endpoint is to compare the change in ventilation distribution and end-expiratory lung impedance at different flows of HFNC and CPAP (Different nasal cannulas in the 2nd phase). These variables will be measured using electrical impedance tomography (EIT) by placing a band around the chest of each participant.
Measured: 5 minnutes
Dead-space washout in the upper airways
Assess whether the transcutaneous CO2 is modified by HFNC, while comparing 3 different nasal cannulas (Symmetrical, Asymmetrical, Single-nostril adapted).
Measured: 5 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start10 Apr 2019
- Primary completion30 Mar 2024
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurent Brochard, MD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03902639
- Sponsor's protocol ID
- REB# 19-006
- Status last verified
- Jul 2026
- First submitted
- 2 Apr 2019
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wongtirawit N, Butterworth R, Vieira F, Schreiber A, Ko M, Brochard L. Influence of leaks and mask design on CO2 clearance during non-invasive ventilation: a combined bench and physiological study. BMJ Open Respir Res. 2026 Aug 19;13(1):e004135. doi: 10.1136/bmjresp-2026-004135.
PubMed 42618283
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study of the Physiological Effects of High Flow Nasal Cannula and Non-invasive Ventilation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03902639
- Acronym / sponsor ID
- REB# 19-006
- Conditions
- Healthy Volunteers
- Keywords
- High flow nasal cannula, Airway pressure, Lung volume, Non-invasive ventilation
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 10 Apr 2019 (actual)
- Primary completion
- 30 Mar 2024 (actual)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 4 Apr 2019 (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.
Respiratory failure is characterized by low levels of oxygen and high levels of carbon dioxide in the blood which causes difficulty breathing. The management of patients with respiratory failure aims at improving oxygenation and changing the effort required to breathe. Mechanical ventilation is a life-saving treatment but may be associated with a high mortality rate, prolonged stay in the intensive care unit (ICU), and infection. Oxygenation techniques to avoid mechanical ventilation include standard oxygen therapy, continuous positive pressure (CPAP), and high-flow nasal cannula oxygen therapy (HFNC). CPAP consists of delivering oxygen through a mask. As compared to standard oxygen therapy, CPAP can promote lung recruitment leading to improved oxygenation and the effect in work of breathing in patients with respiratory failure. Conversely, high-flow nasal cannula oxygen therapy (HFNC) delivers oxygen through nasal prongs. Oxygen is heated and humidified and can be delivered at different flows (from 10 - 60 L/min). As compared to standard oxygen therapy, HFNC can promote some lung recruitment leading to mofiy oxygenation and work of breathing. Therefore, the present study will have 2 phases:
Phase 1:Comparison of the physiological effects of different flows of HFNC to CPAP in healthy volunteers. The investigators hypothesized that the physiological effects of HFNC in the nasopharynx are comparable to that of CPAP at 4 cm H2O.
Phase 2: Comparison of the physiological effects of different nasal interfaces of HFNC (Standard cannula vs. Asymmetrical cannula vs. Single-nostril adapted cannula) in healthy volunteers. The investigators hypothesized that the physiological effects of HFNC in the nasopharynx are comparable to that of CPAP at 4 cm H2O. It was hypothesized that asymmetrical which is the cannula that has a higher cross-sectional area generates higher nasal pharyngeal pressure.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy volunteers responding to advertisement posted through the St. Michael's Hospital Communications board.
Key inclusion criteria (2 listed)
- Healthy volunteers ≥ 18 y-o,
- No evidence of acute or chronic cardiopulmonary disease
Key exclusion criteria (5 listed)
- Active epistaxis, sinus problem, nasal trauma, or deviated septum that would preclude the nasopharyngeal catheter insertion,
- Pregnancy, clinical evidence of respiratory illness, history of respiratory disease, body mass of over 50 kg/m2, ribcage malformation,
- Cardiac pace maker or implantable cardioverter-defibrillator according to EIT manufacturer,
- Allergy to topical lidocaine,
- Claustrophobia that would preclude the use of CPAP or HFNC.
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 |
|---|---|---|
| Phase 1 and 2First, participant will be randomized to a protocol during our study. Participant will breathe normally at different flows of HFNC (20, 40 or 60 L/min) with their mouth open and mouth closed at each flow. They will breathe normally with CPAP at a positive pressure of 4 cm H2O. A lubricated catheter is inserted above the glottis through the nostril to measure ventilatory parameters. EIT is applied to measure inflation of the lung using electromagnetic waves that are not perceptible and are harmless. An ultrasound is done to measure the thickening of your diaphragm and of your abdominal muscles during inspiration and expiration and vocal cords position with and without HFNC (single measurement - around 3 min).During the second step, second catheter is inserted through the nostril to measure esophageal pressure. They will breathe for one additional minute during the closed mouth portions of the experiment while watching the esophageal pressure to ensure steady effort. | Other | – |
| Phase 3In the 3rd phase, according to randomization, volunteers will be masked with either RT041, RT043 or ONIV117 first, followed by the second mask then third mask, also randomize mouth position set to open or closed. The fitting of the masks will be determined based on the manufacturer guidelines and healthy volunteer tolerance. The mask will be adjusted to minimize leaks. At each step, EIT measurements will be recorded at regular breathing over a 10-minute period with an 8-minute washout between devices and 5-minute washout period between mouth positions. The transcutaneous CO2 will be continuously monitored from the earlobe throughout the protocol. | Other | – |
Primary outcome
End expiratory nasopharyngeal pressure (NP)
Time frame: 5 minutes
The primary endpoint is to compare the end expiratory nasopharyngeal pressure (NP) under 60 L/min of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP 4 cmH2O).This will be assessed using a nasopharyngeal catheter.
End expiratory nasopharyngeal pressure (NP)
Time frame: 5min
The primary endpoint is to compare the end expiratory nasopharyngeal pressure (NP) of high flow nasal cannula (HFNC) among the 3 different nasal cannulas (Symmetrical, Asymmetrical, Single-nostril adapted).
3 secondary outcomes
Change in physiologic variables of airway pressure at different flows of HFNC (20, 40, and 60 L/min) and CPAP (4 cmH20). In the phase#2; HFNC 2, and 50 L/min.
Time frame: 5 minutes
Change in end-expiratory lung impedance
Time frame: 5 minnutes
Dead-space washout in the upper airways
Time frame: 5 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Derived from this study: PubMed 42618283Wongtirawit N, Butterworth R, Vieira F, Schreiber A, Ko M, Brochard L. Influence of leaks and mask design on CO2 clearance during non-invasive ventilation: a combined bench and physiological study. BMJ Open Respir Res. 2026 Aug 19;13(1):e004135. doi: 10.1136/bmjresp-2026-004135.
- Individual participant dataSharing planned: No
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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.
Laurent Brochard, MD principal investigator
Unity Health Toronto
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 Healthy Volunteers, run by Unity Health Toronto at 1 site in Canada.
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 2 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. 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 Canada. 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?
This study is still under way. Results are not available in the source record yet.
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?
End expiratory nasopharyngeal pressure (NP) (time frame: 5 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03902639, which also lists 1 linked publication.
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 24 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.