Parkinsonism impairs upper airway and axial motor control, leading to disordered breathing, reduced speech volume, and ineffective cough. Symptoms are poorly addressed by current therapies. This randomized pilot trial tests whether a single session of acute intermittent hypercapnic hypoxia (AIHH) or hypercapnic normoxia (AIHN) improves upper airway and axial motor function in Parkinsonism, and explores biomarker correlates of intervention responsiveness.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
32
Participants randomized to Group 1 will breathe brief bouts of AIHH, involving 15, 1.5-min exposures to 9-10% O2 and 4-5% CO2, alternated with 1 minute of 21% O2 (room air).
Participants randomized to Group 2 will breathe brief bouts of AIHN, involving 15, 1.5-min exposures to 21% O2 and 4-5% CO2, alternated with 1 minute of 21% O2 (room air).
University of Florida
Gainesville, Florida, United States
RECRUITINGNorman Fixel Institute for Neurological Diseases
Gainesville, Florida, United States
RECRUITINGChange in speech loudness
Within-subject differences in sound pressure level (decibels) pre/post intervention and differences between intervention groups (AIHH vs. AIHN) during sustained phonation and connected speech.
Time frame: baseline and 60 minutes post-intervention
Change in maximum phonation duration
Within-subject differences in duration (s) of sustained "ah" pre/post intervention and differences in duration between intervention groups (AIHH vs. AIHN).
Time frame: baseline and 60-minutes post-intervention
Change in peak expiratory flow rate during voluntary cough
Within-subject differences in peak expiratory flow rate (L/s) produced during maximal volitional cough production, pre/post intervention, and between group (AIHH vs. AIHN) differences in peak expiratory flow rate.
Time frame: baseline and 60 minutes post-intervention
Change in Five-Times Sit-to-Stand performance
Within-subject differences in average time (s) to complete 5 times sit-to-stand task, pre/post intervention, and differences between intervention groups (AIHH vs. AIHN).
Time frame: baseline and 60 minutes post-intervention
Change in Timed Up and Go performance
Within-subject differences in duration (s) of Timed Up and Go performance, pre/post intervention. This includes duration of time participants take to stand, walk 3m, turn, walk back 3m, and sit. Differences in duration will also be compared between intervention groups (AIHH vs. AIHN).
Time frame: baseline and 60 minutes post-intervention
Change in fast walking speed
Within-subject differences in duration (s) of 10M walk test, pre/post intervention. Differences in duration will also be compared between intervention groups (AIHH vs. AIHN)
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Time frame: baseline and 60 minutes post-intervention
Correlation between blood-based biomarkers and functional outcomes
Relationship between baseline biomarkers (APOE and BDNF genotype, inflammatory cytokines, serum urate, and circulating α-synuclein) and differences in speech loudness (dB), phonation duration (s), TUG (s), 5x sit-to-stand, and 10M walk test, pre/post intervention in both AIHH and AIHN intervention groups.
Time frame: Baseline and 60 minutes post-intervention; genotype assessed at baseline only
Change in words per breath during connected speech
Within-subject differences in the total number of words produced per breath while reading aloud Grandfather Passage, pre/post intervention. Words per breath will also be measured and compared between intervention groups (AIHH vs. AIHN).
Time frame: baseline and 60 minutes post-intervention
Change in cough volume acceleration during voluntary cough
Within-subject differences in cough volume acceleration (L/s²) during maximal volitional cough production, pre/post intervention, and between groups (AIHH vs. AIHN). Cough volume acceleration is calculated as peak expiratory flow divided by peak expiratory flow rise time.
Time frame: Baseline and 60 minutes post-intervention
Change in airway occlusion pressure
Within-subject differences in mouth occlusion pressure (P0.1) measured in cmH2O, pre/post intervention, and between group differences (AIHH vs. AIHN). P0.1 is the pressure generated at the mouth during the first 0.1 seconds of inspiration against an occluded airway.
Time frame: Baseline and 60 minutes post-intervention
Change in quiet breathing minute ventilation
Within-subject differences in minute-ventilation (L/min ), pre/post intervention, and between group differences (AIHH vs. AIHN) measured during 20 minutes of quiet breathing. Minute ventilation is the calculated using breathing frequency (breaths per minute) x tidal volume (L).
Time frame: Baseline and 60 minutes post-intervention
Association between sleep characteristics and functional outcomes
Relationship between sleep-related metrics (apnea-hypopnea index, oxygen saturation index, and sleep fragmentation) and differences in speech loudness (dB), phonation duration (s), TUG (s), 5x sit-to-stand, and 10M walk test, pre/post intervention in both AIHH and AIHN intervention groups. AHI is calculated by dividing total number of apneas/hypopneas by total hours of sleep. ODI is calculated by dividing the number of times %oxygen drops below baseline by total hours of sleep.
Time frame: Overnight sleep assessment between acclimation and testing visit; functional outcomes measured at baseline and 60 minutes post-intervention