VentilationNCT05168501
Assessing Variability of the Ventilatory Response to Duffin's Rebreathing Procedure
A study testing Rebreathing procedure in people with Ventilation and Reproducibility, run by Food and Drug Administration (FDA) at 1 site in United States.
Trial summary
This study will combine Duffin's rebreathing procedure with additional study procedures, such as quantitative pupillometry, that are planned for subsequent clinical studies in order to confirm feasibility and gather reproducibility data using the procedure. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Ventilation, Reproducibility, Physiology
- What is being tested?
- Rebreathing procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Dec 2021to 18 Feb 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject signs an Institutional Review Board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy, non-smoking man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 32 kg/m2, inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
- Subject must test negative for severe acute respiratory syndrome coronavirus (SARS-CoV-2) by a molecular diagnostic test at check-in (Day -1). If a subject's test comes back inconclusive, it can be repeated at Check-in.
- Female subjects must be of non-childbearing potential or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before Check in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1-month after the last rebreathing procedure; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day -1) until at least 1 month after the end of the study.
- Male subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee) from at least 1 month before Check In (Day -1) until at least 1 month after the last rebreathing procedure.
- Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.
Who cannot join
- Subject has non-reactive or misshapen pupil(s) or damaged orbit structure or surrounding soft tissue is edematous or has an open lesion.
- Subject Duffin rebreathing data is of poor quality or subject does not agree to remain clean-shaven for all days when the Duffin rebreathing procedure is being performed.
- Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before check-in.
- Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening
- Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus [HIV], hepatic or renal impairment) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. This includes subjects with any underlying medical conditions that the Investigator believes would put subjects at increased risk of severe illness from COVID-19 based on the Centers for Disease Control and Prevention (CDC) guidelines.
- Subject has any signs or symptoms that are consistent with COVID-19. These include subjects with fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea may have COVID-19. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
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- Subject tests positive for SARS-CoV-2 by a molecular diagnostic test performed prior to admission.
- Subject has clinical laboratory test results (hematology, serum chemistry and urinalysis) at Screening or Check-In that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
- Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
- Female subject is pregnant or lactating before enrollment in the study.
- Subject has a history of or currently has hypoventilation syndrome, sleep apnea, or chronic obstructive pulmonary disease (COPD) and is on non-invasive ventilation.
- Subject has a history of asthma that has required medication within the last five years.
- Subject has a history of sleep disorders, Panic Disorder, Panic Attacks, Generalized Anxiety Disorder, or any associated DSM diagnosis or condition.
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Clinical Research
West Bend, Wisconsin, 53095
About this study
This study will combine Duffin's rebreathing procedure with additional study procedures, such as quantitative pupillometry, that are planned for subsequent clinical studies in order to confirm feasibility and gather reproducibility data using the procedure. The reproducibility of Duffin rebreathing has been assessed previously by Mahamed and Duffin (2001) performing hyperoxic and hypoxic rebreathing procedures measured once daily for 14 consecutive days and then by Jensen et al. (2010) performing 4 pairs of hyperoxic and hypoxic rebreathing procedures in 1 day followed by 1 pair on 4 additional days separated by weeks to more than a month.
The present study is an unblinded reproducibility assessment to assess variability of the ventilatory response to Duffin's rebreathing procedure. Subjects will report to the study site for screening between Days -28 to -2 and then will return to the site on Day -1 for baseline assessments and check-in. After check-in (Day -1), subjects will remain in study site for PD assessments on Day 1 and check out on Day 2.
Paired rebreathing procedures (i.e., at two different isoxic end tidal PO2 [partial pressure oxygen] levels) will be performed on Day 1 at 0, 2, 4, and 6 hours. An additional pair of rebreathing procedures will be performed on Day 2 before checkout (approximately 24 hours). Subjects will not be administered any drugs in this study.
- Conditions
- Ventilation, Reproducibility, Physiology
- Being tested
- Rebreathing procedure
- Keywords
- Duffin's rebreathing procedure, Ventilation, Pupillometry, Physiology
- Medical subject headings
- Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rebreathing procedureOther
Paired Duffin's rebreathing procedures performed two different isoxic end tidal PO2 levels (i.e., hyperoxic and hypoxic conditions) will be performed on Day 1 at 0, 2, 4, 6, and 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Lead-In | Experimental | Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) will be conducted under hyperoxic and hypoxic conditions over the course of a day to confirm feasibility and gather reproducibility data using the procedure. Receives: Other: Rebreathing procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Minute Ventilation
Minute ventilation during the rebreathing assessment when end tidal PCO2 (partial pressure carbon dioxide) is less than the ventilatory recruitment threshold (represents non-chemoreflex drives to breathe; 'flat' portion of minute ventilation versus end tidal PCO2 relationship). Data was analyzed using linear-mixed effects regression of baseline minute ventilation with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Measured: 0, 2, 4, 6 and 24 hours
Ventilatory Recruitment Threshold
The end tidal PCO2 point above which minute ventilation starts to increase linearly with further increases in end tidal PCO2. Data was analyzed using linear-mixed effects regression of ventilatory recruitment threshold with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Measured: 0, 2, 4, 6 and 24 hours
Slope of the PCO2-ventilatory Response Curve
Slope of the minute ventilation versus end tidal PCO2 curve that reflects the increase in minute ventilation relative to the increase in end tidal PCO2. Data was analyzed using linear-mixed effects regression of Slope of the PCO2-ventilatory response curve with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Measured: 0, 2, 4, 6 and 24 hours
Extrapolated Ventilatory Recruitment Threshold
Intersection of the slope of the PCO2-ventilation response curve with the X axis. Data was analyzed using linear-mixed effects regression of extrapolated ventilatory recruitment threshold with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Measured: 0, 2, 4, 6 and 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start27 Dec 2021
- Primary completion18 Feb 2022
- Study completion18 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for VentilationStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is an unblinded reproducibility assessment to assess variability of the ventilatory response to Duffin's rebreathing procedure. The lead-in reproducibility assessment will have up to 10 healthy volunteer participants.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Food and Drug Administration (FDA)
- Sponsor type
- US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Responsible party
- Sponsor
- Investigators
- Jan Matousek, D.O., Principal investigator, Spaulding Clinical Research LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05168501
- Sponsor's protocol ID
- SCR-013
- Status last verified
- Dec 2021
- First submitted
- 13 Dec 2021
- Last updated
- 15 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Duffin J. Measuring the respiratory chemoreflexes in humans. Respir Physiol Neurobiol. 2011 Jul 31;177(2):71-9. doi: 10.1016/j.resp.2011.04.009. Epub 2011 Apr 14.
PubMed 21514404Mahamed S, Duffin J. Repeated hypoxic exposures change respiratory chemoreflex control in humans. J Physiol. 2001 Jul 15;534(Pt. 2):595-603. doi: 10.1111/j.1469-7793.2001.00595.x.
PubMed 11454975Jensen D, Mask G, Tschakovsky ME. Variability of the ventilatory response to Duffin's modified hyperoxic and hypoxic rebreathing procedure in healthy awake humans. Respir Physiol Neurobiol. 2010 Feb 28;170(2):185-97. doi: 10.1016/j.resp.2009.12.007. Epub 2009 Dec 24.
PubMed 20035904
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Variability of the Ventilatory Response to Duffin's Rebreathing Procedure
- ClinicalTrials.gov ID
- NCT05168501
- Acronym / sponsor ID
- SCR-013
- Conditions
- Ventilation, Reproducibility, Physiology
- Keywords
- Duffin's rebreathing procedure, Ventilation, Pupillometry, Physiology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Food and Drug Administration (FDA)US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Study start
- 27 Dec 2021 (actual)
- Primary completion
- 18 Feb 2022 (actual)
- Study completion
- 18 Feb 2022 (actual)
- First posted
- 23 Dec 2021 (actual)
- Results
- Posted 15 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will combine Duffin's rebreathing procedure with additional study procedures, such as quantitative pupillometry, that are planned for subsequent clinical studies in order to confirm feasibility and gather reproducibility data using the procedure. The reproducibility of Duffin rebreathing has been assessed previously by Mahamed and Duffin (2001) performing hyperoxic and hypoxic rebreathing procedures measured once daily for 14 consecutive days and then by Jensen et al. (2010) performing 4 pairs of hyperoxic and hypoxic rebreathing procedures in 1 day followed by 1 pair on 4 additional days separated by weeks to more than a month.
The present study is an unblinded reproducibility assessment to assess variability of the ventilatory response to Duffin's rebreathing procedure. Subjects will report to the study site for screening between Days -28 to -2 and then will return to the site on Day -1 for baseline assessments and check-in. After check-in (Day -1), subjects will remain in study site for PD assessments on Day 1 and check out on Day 2.
Paired rebreathing procedures (i.e., at two different isoxic end tidal PO2 [partial pressure oxygen] levels) will be performed on Day 1 at 0, 2, 4, and 6 hours. An additional pair of rebreathing procedures will be performed on Day 2 before checkout (approximately 24 hours). Subjects will not be administered any drugs in this study.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is an unblinded reproducibility assessment to assess variability of the ventilatory response to Duffin's rebreathing procedure. The lead-in reproducibility assessment will have up to 10 healthy volunteer participants.
| Arm | Type | Receives |
|---|---|---|
| Lead-In | Experimental | Other: Rebreathing procedureMultiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) will be conducted under hyperoxic and hypoxic conditions over the course of a day to confirm feasibility and gather reproducibility data using the procedure. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject signs an Institutional Review Board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy, non-smoking man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 32 kg/m2, inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
- Subject must test negative for severe acute respiratory syndrome coronavirus (SARS-CoV-2) by a molecular diagnostic test at check-in (Day -1). If a subject's test comes back inconclusive, it can be repeated at Check-in.
Key exclusion criteria (13 listed)
- Subject has non-reactive or misshapen pupil(s) or damaged orbit structure or surrounding soft tissue is edematous or has an open lesion.
- Subject Duffin rebreathing data is of poor quality or subject does not agree to remain clean-shaven for all days when the Duffin rebreathing procedure is being performed.
- Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before check-in.
- Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening
- Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus [HIV], hepatic or renal impairment) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. This includes subjects with any underlying medical conditions that the Investigator believes would put subjects at increased risk of severe illness from COVID-19 based on the Centers for Disease Control and Prevention (CDC) guidelines.
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 |
|---|---|---|
| Rebreathing procedurePaired Duffin's rebreathing procedures performed two different isoxic end tidal PO2 levels (i.e., hyperoxic and hypoxic conditions) will be performed on Day 1 at 0, 2, 4, 6, and 24 hours. | Other | Lead-In |
Primary outcome
Baseline Minute Ventilation
Time frame: 0, 2, 4, 6 and 24 hours
Minute ventilation during the rebreathing assessment when end tidal PCO2 (partial pressure carbon dioxide) is less than the ventilatory recruitment threshold (represents non-chemoreflex drives to breathe; 'flat' portion of minute ventilation versus end tidal PCO2 relationship). Data was analyzed using linear-mixed effects regression of baseline minute ventilation with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Ventilatory Recruitment Threshold
Time frame: 0, 2, 4, 6 and 24 hours
The end tidal PCO2 point above which minute ventilation starts to increase linearly with further increases in end tidal PCO2. Data was analyzed using linear-mixed effects regression of ventilatory recruitment threshold with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Slope of the PCO2-ventilatory Response Curve
Time frame: 0, 2, 4, 6 and 24 hours
Slope of the minute ventilation versus end tidal PCO2 curve that reflects the increase in minute ventilation relative to the increase in end tidal PCO2. Data was analyzed using linear-mixed effects regression of Slope of the PCO2-ventilatory response curve with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Extrapolated Ventilatory Recruitment Threshold
Time frame: 0, 2, 4, 6 and 24 hours
Intersection of the slope of the PCO2-ventilation response curve with the X axis. Data was analyzed using linear-mixed effects regression of extrapolated ventilatory recruitment threshold with random effects for between subject, between day, and between occasion variability. Reported value is the mean for the treatment group across all individuals, days, and times.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21514404Duffin J. Measuring the respiratory chemoreflexes in humans. Respir Physiol Neurobiol. 2011 Jul 31;177(2):71-9. doi: 10.1016/j.resp.2011.04.009. Epub 2011 Apr 14.
- Background: PubMed 11454975Mahamed S, Duffin J. Repeated hypoxic exposures change respiratory chemoreflex control in humans. J Physiol. 2001 Jul 15;534(Pt. 2):595-603. doi: 10.1111/j.1469-7793.2001.00595.x.
- Background: PubMed 20035904Jensen D, Mask G, Tschakovsky ME. Variability of the ventilatory response to Duffin's modified hyperoxic and hypoxic rebreathing procedure in healthy awake humans. Respir Physiol Neurobiol. 2010 Feb 28;170(2):185-97. doi: 10.1016/j.resp.2009.12.007. Epub 2009 Dec 24.
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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.
Jan Matousek, D.O. principal investigator
Spaulding Clinical Research LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rebreathing procedure in people with Ventilation and Reproducibility, run by Food and Drug Administration (FDA) at 1 site in United States.
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 8 inclusion and 13 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 15 Jul 2024. 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 United States. 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?
Yes. Results are posted in the registry (first posted 15 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Baseline Minute Ventilation (time frame: 0, 2, 4, 6 and 24 hours). The study lists 4 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 NCT05168501, which also lists 3 linked publications.
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 15 Jul 2024.