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

Not Applicable

Recruiting

• Conditions: Traumatic Brain Injury
• Interventions: Other: Acute Intermittent Hypoxia (AIH); Other: Sham AIH; Behavioral: Task specific Airway Protection Training

• Registration Number: NCT06520358
• Lead Sponsor: University of Florida

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).

Detailed Description

Recent studies have found that acute intermittent hypoxia (AIH)-or repetitive exposure to brief episodes of low inspired oxygen--is a promising new strategy that can help restore motor function by promoting neuroplasticity throughout the central nervous system (CNS). Both rodent and human studies show that motor function is further enhanced when AIH is paired with task-specific training/rehabilitation (TST). Therefore, this study will investigate the therapeutic potential of combining AIH with a task-specific airway protection training. We propose that the combined use of AIH + TST will enhance the magnitude and duration of TST training alone in individuals with chronic traumatic brain injury.

Study Timeline

• Study First Submitted: 2024-07-19
• Study First Submitted QC: 2024-07-24
• Study First Posted: 2024-07-25
• Study Start: 2024-08-30
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-25
• Primary Completion: 2025-03-30
• Study Completion: 2025-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sham AIH + TST	Sham AIH	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.
AIH + TST	Task specific Airway Protection Training	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.
Sham AIH + TST	Task specific Airway Protection Training	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.
AIH + TST	Acute Intermittent Hypoxia (AIH)	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.

Primary Outcome Measures

Name	Time	Method
Duration of laryngeal vestibule closure (dLVC)	Pre-intervention, 1 day after intervention block and 1-week post intervention	Time in (msec) the laryngeal vestibule stays closed during a swallow
Time to laryngeal vestibule closure (Time-to-LVC)	Pre-intervention, 1 day after intervention block and 1-week post intervention	Time in (msec) it takes to close the laryngeal vestibule after swallow initiation

Secondary Outcome Measures

Name	Time	Method
Penetration-Aspiration Scale Scores	Pre-intervention, 1 day after intervention block and 1-week post intervention	The penetration-aspiration scale (PAS) will be used to assess penetration or aspiration; the PAS is an 8-point scale that ranges from 1 (no penetration/aspiration) to 8 (aspiration with no cough response).

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Jacksonville, Florida, United States