Trial Outcomes & Findings for Assessing Variability of the Ventilatory Response to Duffin's Rebreathing Procedure (NCT NCT05168501)

Last Updated: 2024-07-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

7 participants

Primary outcome timeframe

0, 2, 4, 6 and 24 hours

Results posted on

2024-07-15

Participant Flow

Enrollment was halted after 7 participants as sufficient experience with the experimental technique was obtained to move on to subsequent studies.

Participant milestones

Participant milestones
Measure	Lead-In 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. Rebreathing procedure: 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.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Assessing Variability of the Ventilatory Response to Duffin's Rebreathing Procedure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead-In n=7 Participants 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. Rebreathing procedure: 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.
Age, Continuous	30.6 years STANDARD_DEVIATION 8.7 • n=99 Participants
Sex: Female, Male Female	2 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	5 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants
Region of Enrollment United States	7 participants n=99 Participants

PRIMARY outcome

Timeframe: 0, 2, 4, 6 and 24 hours

Population: All participants who successfully completed one rebreathing assessment.

Outcome measures

Outcome measures
Measure	Hyperoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hyperoxic conditions (maintained isoxic 150 mmHg) at 0, 2, 4, 6, and 24 hours.	Hypoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hypoxic conditions (maintained isoxic 50 mmHg) at 0, 2, 4, 6, and 24 hours.
Baseline Minute Ventilation	11.6 L/min Standard Deviation 3.4	12.0 L/min Standard Deviation 2.9

PRIMARY outcome

Timeframe: 0, 2, 4, 6 and 24 hours

Population: All participants who successfully completed one rebreathing assessment.

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.

Outcome measures

Outcome measures
Measure	Hyperoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hyperoxic conditions (maintained isoxic 150 mmHg) at 0, 2, 4, 6, and 24 hours.	Hypoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hypoxic conditions (maintained isoxic 50 mmHg) at 0, 2, 4, 6, and 24 hours.
Ventilatory Recruitment Threshold	43.0 mmHg Standard Deviation 3.0	38.1 mmHg Standard Deviation 1.7

PRIMARY outcome

Timeframe: 0, 2, 4, 6 and 24 hours

Population: All participants who successfully completed one rebreathing assessment.

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.

Outcome measures

Outcome measures
Measure	Hyperoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hyperoxic conditions (maintained isoxic 150 mmHg) at 0, 2, 4, 6, and 24 hours.	Hypoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hypoxic conditions (maintained isoxic 50 mmHg) at 0, 2, 4, 6, and 24 hours.
Slope of the PCO2-ventilatory Response Curve	3.19 L/min/mmHg Standard Deviation 2.46	3.28 L/min/mmHg Standard Deviation 2.41

PRIMARY outcome

Timeframe: 0, 2, 4, 6 and 24 hours

Population: All participants who successfully completed one rebreathing assessment.

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.

Outcome measures

Outcome measures
Measure	Hyperoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hyperoxic conditions (maintained isoxic 150 mmHg) at 0, 2, 4, 6, and 24 hours.	Hypoxic Rebreathing n=7 Participants Multiple rebreathing procedures using methodology developed by Duffin (referred to as Duffin's rebreathing procedure) were conducted under hypoxic conditions (maintained isoxic 50 mmHg) at 0, 2, 4, 6, and 24 hours.
Extrapolated Ventilatory Recruitment Threshold	36.8 mmHg Standard Deviation 7.1	32.7 mmHg Standard Deviation 5.9

Adverse Events

Hyperoxic Rebreathing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Hypoxic Rebreathing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David Strauss, MD, PhD

U.S. Food and Drug Administration

Phone: 301-796-6323

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place