Acute Intermittent Hypoxia to Improve Airway Protection in Chronic Traumatic Brain Injury

NCT06520358 | Completed

• 1 other identifier: IRB202301156
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Acute intermittent hypoxia (AIH) involves 1-2min of breathing low oxygen air to stimulate neuroplasticity. Animal and human studies show that AIH improves motor function after neural injury, particularly when paired with task-specific training. Using a double blind cross-over study we will test whether AIH and task-specific airway protection training improves airway protection more than training alone in individuals with chronic mild-moderate traumatic brain injury (TBI).

Conditions

Traumatic Brain Injury

Keywords

acute intermittent hypoxia; rehabilitation; airway protection; dysphagia

Outcome Measures

Primary Outcomes (2)

• Duration of laryngeal vestibule closure (dLVC)

  Time in (msec) the laryngeal vestibule stays closed during a swallow

  Pre-intervention, 1 day after intervention block and 1-week post intervention

• Time to laryngeal vestibule closure (Time-to-LVC)

  Time in (msec) it takes to close the laryngeal vestibule after swallow initiation

  Pre-intervention, 1 day after intervention block and 1-week post intervention

Secondary Outcomes (1)

• Penetration-Aspiration Scale Scores

  Pre-intervention, 1 day after intervention block and 1-week post intervention

Study Arms (2)

AIH + TST

ACTIVE COMPARATOR

Participants will complete a 5-day intervention blocks where they receive daily AIH followed by task specific airway protection training 60 minutes after the AIH exposure. Each exposure involves a 1-minute delivery of low oxygen (9-11% inspired O2), followed by a 1.5-min interval of room air breathing (21% O2). This method of waiting 45-60 minutes after the delivery of AIH and prior to engaging in task-specific training/rehabilitation enables sufficient time to increase brain derived neurotrophic factor (BDNF) following AIH, thereby augmenting the impact of task-specific training.

Other: Acute Intermittent Hypoxia (AIH); Behavioral: Task specific Airway Protection Training

Sham AIH + TST

SHAM COMPARATOR

Participants will complete a 5-day intervention blocks where they receive sham AIH followed by task specific airway protection training 60 minutes after the AIH sham exposure. Sham AIH will be delivered using methods identical to AIH, except a normoxic gas mixture (\~21% O2) will be delivered. The gas mixture with normoxic air will effectively serve as a sham.

Behavioral: Task specific Airway Protection Training; Other: Sham AIH

Interventions

Acute Intermittent Hypoxia (AIH) OTHER

Acute intermittent hypoxia refers to brief (acute), repetitive (intermittent) episodes of breathing oxygen-deprived air (hypoxia) alternating with breathing ambient room air.

AIH + TST

Task specific Airway Protection Training BEHAVIORAL

The vLVC maneuver involves training participants to volitionally prolong closure of the laryngeal vestibule during swallowing, beginning with swallow onset and sustaining closure for at least 2 seconds.

Also known as: volitional laryngeal vestibule closure (vLVC) training

AIH + TST; Sham AIH + TST

Sham AIH OTHER

Sham AIH will be delivered using methods identical to AIH, except a normoxic gas mixture (\~21% O2) will be delivered. The gas mixture with normoxic air will effectively serve as a sham.

Sham AIH + TST

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 21-80 years
• A mild to moderate traumatic brain injury (TBI) confirmed by medical records
• A Glasgow Coma Scale score between 9-15
• Able to consent independently
• Women of child-bearing age must be comfortable confirming a negative pregnancy prior to participating in the study

You may not qualify if:

• Other neurological diagnoses or a diagnosis of a severe psychiatric disorder
• Severe aphasia preventing a participant from understanding the protocol and consent form
• Pre-existing hypoxic pulmonary disease
• History of obstructive lung diseases such as chronic obstructive pulmonary disease (COPD) or significant asthma)
• Severe hypertension (\>160/100)
• History of head and neck cancer
• Allergy to barium sulfate
• Ischemic cardiac disease

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (3)

• Vose AK, Welch JF, Nair J, Dale EA, Fox EJ, Muir GD, Trumbower RD, Mitchell GS. Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Exp Neurol. 2022 Jan;347:113891. doi: 10.1016/j.expneurol.2021.113891. Epub 2021 Oct 9.

  PMID: 34637802 BACKGROUND

• Welch JF, Sutor TW, Vose AK, Perim RR, Fox EJ, Mitchell GS. Synergy between Acute Intermittent Hypoxia and Task-Specific Training. Exerc Sport Sci Rev. 2020 Jul;48(3):125-132. doi: 10.1249/JES.0000000000000222.

  PMID: 32412926 BACKGROUND

• Vose A, Humbert I. "Hidden in Plain Sight": A Descriptive Review of Laryngeal Vestibule Closure. Dysphagia. 2019 Jun;34(3):281-289. doi: 10.1007/s00455-018-9928-1. Epub 2018 Jul 30.

  PMID: 30062547 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Deglutition Disorders

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Study Officials

• Alicia Z Vose, Ph.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and assessors will be blinded to group allocation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The pilot study will utilize a double-blind, placebo-controlled, randomized-order, repeated-measures, cross-over experimental design

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 25, 2024
• Study Start: August 30, 2024
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: January 9, 2026

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)