Parkinson Disease, Parkinsonism
Conditions
Keywords
Axial function, Upper airway, Breathing, Acute Intermittent Hypercapnic Hypoxia
Brief summary
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.
Interventions
OTHERAcute intermittent hypercapnic hypoxia (AIHH)
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).
OTHERAcute intermittent hypercapnic normoxia (AIHN)
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).
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Each arm involves hypercapnia, while only one includes mild hypoxia. The addition of slightly elevated CO2 in each arm facilitates participant blinding.
Intervention model description
Single blind, randomized parallel study design
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. adults 40 to 75 years of age (the latter to reduce the likelihood of cardiovascular disease) 2. diagnosis of idiopathic Parkinsonism with Hoehn and Yahr stages 2-4 3. medically stable with physician clearance 4. ability to ambulate at least 10 feet with/without assistance 5. ability to follow directions 6. willing to abstain from blood donation for the duration of the study
Exclusion criteria
1. additional neurologic conditions 2. severe illness or infection, including respiratory/cardiovascular/lung disease, or uncontrolled hypertension 3. inspiratory stridor 4. pregnancy due to unknown tAIH effects on a fetus, although females of childbearing age will not be excluded\* 5. cigarette smoking or vaping within 5 years 6. history of head/neck/lung cancer with the exception of basal cell carcinoma 7. is currently participating in another research study that could influence the results from this study 8. has deep brain stimulation electrodes implanted or has a history of deep brain stimulation 9. faints or becomes lightheaded at the sight of blood * If a female of childbearing potential indicates there is a chance she could be pregnant, she will be provided a pregnancy test and allowed to continue in the study if negative. This is because the fetal risks associated with intermittent hypoxia are unknown.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in speech loudness | baseline and 60 minutes post-intervention | 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. |
| Change in maximum phonation duration | baseline and 60-minutes post-intervention | Within-subject differences in duration (s) of sustained "ah" pre/post intervention and differences in duration between intervention groups (AIHH vs. AIHN). |
| Change in peak expiratory flow rate during voluntary cough | baseline and 60 minutes post-intervention | 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. |
| Change in Five-Times Sit-to-Stand performance | baseline and 60 minutes post-intervention | 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). |
| Change in Timed Up and Go performance | baseline and 60 minutes post-intervention | 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). |
| Change in fast walking speed | baseline and 60 minutes post-intervention | 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) |
| Correlation between blood-based biomarkers and functional outcomes | Baseline and 60 minutes post-intervention; genotype assessed at baseline only | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in words per breath during connected speech | baseline and 60 minutes post-intervention | 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). |
| Change in cough volume acceleration during voluntary cough | Baseline and 60 minutes post-intervention | 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. |
| Change in airway occlusion pressure | Baseline and 60 minutes post-intervention | 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. |
| Change in quiet breathing minute ventilation | Baseline and 60 minutes post-intervention | 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). |
| Association between sleep characteristics and functional outcomes | Overnight sleep assessment between acclimation and testing visit; functional outcomes measured at baseline and 60 minutes post-intervention | 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. |
Countries
United States
Contacts
CONTACTMichlela Mir, CCC-SLP, PhD
CONTACTAlysha Bogard, PhD
PRINCIPAL_INVESTIGATORMichela Mir, CCC-SLP
University of Florida
PRINCIPAL_INVESTIGATORAlysha Bogard, PhD
University of Florida
Outcome results
None listed