Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07674264

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinsonian Disorders Parkinsonism Pathologic Processes Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Aspiration Respiratory Tract Diseases Synucleinopathies

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Norman Fixel Institute for Neurological Diseases, Gainesville, Florida, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • adults 40 to 75 years of age (the latter to reduce the likelihood of cardiovascular disease)
  • diagnosis of idiopathic Parkinsonism with Hoehn and Yahr stages 2-4
  • medically stable with physician clearance
  • ability to ambulate at least 10 feet with/without assistance
  • ability to follow directions
  • willing to abstain from blood donation for the duration of the study

Exclusion criteria

  • additional neurologic conditions
  • severe illness or infection, including respiratory/cardiovascular/lung disease, or uncontrolled hypertension
  • inspiratory stridor
  • pregnancy due to unknown tAIH effects on a fetus, although females of childbearing age will not be excluded*
  • cigarette smoking or vaping within 5 years
  • history of head/neck/lung cancer with the exception of basal cell carcinoma
  • is currently participating in another research study that could influence the results from this study
  • has deep brain stimulation electrodes implanted or has a history of deep brain stimulation
  • 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.

Treatment and study plan

Acute intermittent hypercapnic hypoxia (AIHH)

Other

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).

Acute intermittent hypercapnic normoxia (AIHN)

Other

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).

Primary outcomes

  1. Change in speech loudness

    Time frame: 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.

  2. Change in maximum phonation duration

    Time frame: 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).

  3. Change in peak expiratory flow rate during voluntary cough

    Time frame: 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.

  4. Change in Five-Times Sit-to-Stand performance

    Time frame: 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).

  5. Change in Timed Up and Go performance

    Time frame: 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).

  6. Change in fast walking speed

    Time frame: 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)

  7. Correlation between blood-based biomarkers and functional outcomes

    Time frame: 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 outcomes

  1. Change in words per breath during connected speech

    Time frame: 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).

  2. Change in cough volume acceleration during voluntary cough

    Time frame: 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.

  3. Change in airway occlusion pressure

    Time frame: 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.

  4. Change in quiet breathing minute ventilation

    Time frame: 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).

  5. Association between sleep characteristics and functional outcomes

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Alysha Bogard, PhD

CONTACT

[email protected]

3038279875

Michlela Mir, CCC-SLP, PhD

CONTACT

[email protected]

352-273-6095

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jun 29, 2026
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.