Acute Intermittent Hypoxia for Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Florida
Disqualifiers: Neurological, Psychiatric, Pulmonary, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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).
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Is Acute Intermittent Hypoxia (AIH) safe for humans?
Acute Intermittent Hypoxia (AIH) is considered a safe and non-invasive treatment approach, as it involves brief, repetitive periods of breathing reduced oxygen air alternated with normal oxygen levels.
12345How is the treatment Acute Intermittent Hypoxia (AIH) different from other treatments for traumatic brain injury?
Acute Intermittent Hypoxia (AIH) is unique because it involves exposing patients to short periods of low oxygen levels, which may help the brain adapt and recover after injury. This approach is different from other treatments like hyperbaric oxygen therapy, which uses high oxygen levels to aid recovery.
678910Eligibility Criteria
This trial is for individuals with chronic mild to moderate traumatic brain injury (TBI) who may benefit from a new therapy. Participants should be stable and not have other medical conditions that could interfere with the study.Inclusion Criteria
I am not pregnant and can provide a negative pregnancy test.
I am between 21 and 80 years old.
A Glasgow Coma Scale score between 9-15
+2 more
Exclusion Criteria
Severe aphasia preventing a participant from understanding the protocol and consent form
I have a lung condition that causes low oxygen levels.
I have a history of serious lung problems like COPD or severe asthma.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive daily AIH or sham AIH followed by task-specific airway protection training over 5-day intervention blocks
1 week
5 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 week
1 visit (in-person)
Participant Groups
The study tests if breathing low oxygen air in short bursts (Acute Intermittent Hypoxia or AIH) combined with special training can improve airway protection better than training alone after TBI, using a double-blind cross-over design.
2Treatment groups
Active Control
Placebo Group
Group I: AIH + TSTActive Control2 Interventions
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.
Group II: Sham AIH + TSTPlacebo Group2 Interventions
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.
Acute Intermittent Hypoxia (AIH) is already approved in United States for the following indications:
🇺🇸 Approved in United States as Acute Intermittent Hypoxia for:
- Respiratory recovery in spinal cord injury
- Improvement in motor function after spinal cord injury
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of FloridaJacksonville, FL
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Who Is Running the Clinical Trial?
University of FloridaLead Sponsor
References
APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. [2023]Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability.
APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia. [2023]Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.
Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex. [2022]Acute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex.
Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation. [2022]Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P
Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia. [2021]Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH).
Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude. [2018]Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH.
Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure. [2012]Brain hypoxia (BH) can aggravate outcome after severe traumatic brain injury (TBI). Whether BH or reduced brain oxygen (Pbto(2)) is an independent outcome predictor or a marker of disease severity is not fully elucidated.
Functional Outcomes in Patients Admitted to the Intensive Care Unit with Traumatic Brain Injury and Exposed to Hyperoxia: A Retrospective Multicentre Cohort Study. [2021]Supplemental oxygen administration to critically ill patients is ubiquitous in the intensive care unit (ICU). Uncertainty persists as to whether hyperoxia is benign in patients with traumatic brain injury (TBI), particularly in regard to their long-term functional neurological outcomes.
Hypoxia alters the expression of inhibitor of apoptosis proteins after brain trauma in the mouse. [2016]Hypoxia worsens brain injury following trauma, but the mechanisms remain unclear. The purpose of this study was to determine the effect of traumatic brain injury (TBI) and secondary hypoxia (9% oxygen) on apoptosis-related protein expression, cell death, and behavior. Using a murine weight-drop model, TBI led to an early (6 h) increase followed by a later (24 h) decrease in neuronal apoptosis inhibitor protein (NAIP) expression in the olfactory and motor cortex; in contrast, TBI led to a sustained (6 h to 7 days) increase in NAIP in the striatum. The peak increase in the expression of NAIP (6-12 h) following TBI alone was delayed (1-7 days) when hypoxia was added to TBI. Hypoxia following TBI further depleted other apoptosis inhibitor proteins (IAPs) and activated caspases, as well as increased contusion size and worsened cell death. Hypoxia added to TBI also increased motor and feeding activity on days 2 and 4 compared to TBI alone. Hypoxia without TBI had no effect on the expression of IAPs or cell death. These findings show that IAPs have a potential role in the increased vulnerability of brain cells to hypoxia following TBI, and have implications for configuring future therapies for TBI.
A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. [2015]Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO2) for severe traumatic brain injury (TBI) occurs after rather than during treatment. The brain appears better able to use baseline O2 levels following HBO2 treatments. In this study, the authors evaluate the combination of HBO2 and normobaric hyperoxia (NBH) as a single treatment.