Cross-System Effects of Acute Intermittent Hypercapnia-Based Interventions in PD

A Pilot Study of Acute Intermittent Hypercapnia-Based Interventions on Upper Airway and Axial Motor Function in Parkinson's Disease

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 Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Parkinsonism
• Intervention / Treatment: Other: Acute intermittent hypercapnic hypoxia (AIHH); Other: Acute intermittent hypercapnic normoxia (AIHN)

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michlela Mir, CCC-SLP, PhD; Phone Number: 352-273-6095; Email: michela.mir@ufl.edu
• Study Contact Backup: Name: Alysha Bogard, PhD; Phone Number: 3038279875; Email: abogard@ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: Alysha Bogard, PhD; Phone Number: 3038279875; Email: abogard@ufl.edu
      • Contact: Michela Mir, CCC-SLP, PhD; Phone Number: 352-273-6095; Email: michela.mir@ufl.edu
      • Principal Investigator: Michela Mir, CCC-SLP
      • Principal Investigator: Alysha Bogard, PhD
    • Gainesville, Florida, United States, 80303-2181
      • Recruiting
      • Norman Fixel Institute for Neurological Diseases
      • Contact: Alysha Bogard, PhD; Phone Number: 3038279875; Email: abogard@ufl.edu
      • Principal Investigator: Michela Mir, CCC-SLP
      • Principal Investigator: Alysha Bogard, PhD
      • Contact: Michela Mir, CCC-SLP, PhD; Phone Number: 303-827-9875; Email: michela.mir@ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Acute Intermittent Hypercapnic Hypoxia; Each participant randomly allocated to this arm will breathe brief bouts of mild acute intermittent hypercapnic hypoxia as the intervention, with PRE and POST testing of upper airway, axial function, and blood-based biomarkers.	Other: Acute 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).
Active Comparator: Group 2: Acute Intermittent Hypercapnic Normoxia; Each participant randomly allocated to this arm will breathe brief bouts of mild acute intermittent hypercapnic normoxia as the intervention, with PRE and POST testing of upper airway, axial function, and blood-based biomarkers.	Other: Acute 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change 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.	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).	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.	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).	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).	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)	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.	Baseline and 60 minutes post-intervention; genotype assessed at baseline only

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	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).	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.	Overnight sleep assessment between acclimation and testing visit; functional outcomes measured at baseline and 60 minutes post-intervention

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Michela Mir, CCC-SLP, University of Florida; Principal Investigator: Alysha Bogard, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Breathing; Upper airway; Axial function; Acute Intermittent Hypercapnic Hypoxia
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Pathological Conditions, Signs and Symptoms; Respiratory Aspiration; Parkinson Disease; Parkinsonian Disorders
• Other Study ID Numbers: IRB202600117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data may be made available upon reasonable request following publication of the primary study results and with approval of the study investigators and University of Florida.

IPD Sharing Time Frame

Available Starting:

12 months after publication of the primary study results.

Available Ending:

5 years after publication of the primary study results.

• IPD Sharing Access Criteria: De-identified individual participant data (IPD) that underlie the results reported in published manuscripts will be available beginning 12 months following publication of the primary study results and ending 5 years thereafter. Shared data may include demographic characteristics, intervention assignment, speech outcomes, cough outcomes, respiratory outcomes, mobility outcomes, sleep metrics, blood-based biomarker measures, and associated data dictionaries. Investigators who provide a methodologically sound proposal for secondary analyses may request access. Requests will be reviewed by the study investigators and the University of Florida as applicable. Approved investigators will receive access to de-identified datasets and supporting documentation through a secure data-sharing mechanism following execution of any required data use agreements and institutional approvals.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No