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

NCT07674264 | Recruiting

• 1 other identifier: IRB202600117
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Parkinson Disease; Parkinsonism

Keywords

Axial function; Upper airway; Breathing; Acute Intermittent Hypercapnic Hypoxia

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• Change in words per breath during connected speech

  baseline and 60 minutes post-intervention

• Change in cough volume acceleration during voluntary cough

  Baseline and 60 minutes post-intervention

• Change in airway occlusion pressure

  Baseline and 60 minutes post-intervention

• Change in quiet breathing minute ventilation

  Baseline and 60 minutes post-intervention

• 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

Study Arms (2)

Group 1: Acute Intermittent Hypercapnic Hypoxia

EXPERIMENTAL

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)

Group 2: Acute Intermittent Hypercapnic Normoxia

ACTIVE COMPARATOR

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)

Interventions

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).

Group 1: Acute Intermittent Hypercapnic Hypoxia

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).

Group 2: Acute Intermittent Hypercapnic Normoxia

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (2)

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Norman Fixel Institute for Neurological Diseases

Gainesville, Florida, 80303-2181, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michela Mir, CCC-SLP

  University of Florida

  PRINCIPAL INVESTIGATOR

• Alysha Bogard, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michlela Mir, CCC-SLP, PhD

CONTACT

352-273-6095; michela.mir@ufl.edu

Alysha Bogard, PhD

CONTACT

3038279875; abogard@ufl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Each arm involves hypercapnia, while only one includes mild hypoxia. The addition of slightly elevated CO2 in each arm facilitates participant blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single blind, randomized parallel study design

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 29, 2026
• Study Start: June 20, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Available Starting: 12 months after publication of the primary study results. Available Ending: 5 years after publication of the primary study results.
• 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.

Locations

US (2)