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 Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
7
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.
Spaulding Clinical Research
West Bend, Wisconsin, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 0, 2, 4, 6 and 24 hours
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