Brain Injuries, TraumaticAIHNCT04890639
Acute Intermittent Hypoxia in Traumatic Brain Injury
A study testing Acute Intermittent Hypoxia in people with Brain Injuries, Traumatic, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial summary
This study is designed to answer questions related to safety and preliminary efficacy of Acute Intermittent Hypoxia (AIH) in Traumatic Brain Injury (TBI) survivors. First, we aim to establish whether brief reductions in inhaled oxygen concentration can be safely tolerated in TBI survivors. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Brain Injuries, Traumatic
- What is being tested?
- Acute Intermittent Hypoxia
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Mar 2022to 29 Jan 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-65 years
- A first time, mild to moderate traumatic brain injury (TBI) confirmed by medical records
- When available, a Glasgow Coma Scale score between 9-15
- Able to use a keyboard
- Able to understand and communicate in English
- Able to consent independently
Show all 9Show fewer
- Able to leave a research visit with a companion/group transportation
- Women of child-bearing age must be comfortable confirming a negative pregnancy prior to participating in the study
- Not involved in any other research intervention study testing neurobehavioral functioning
Who cannot join
- Other neurological diagnoses or a diagnosis of severe psychiatric disorder (e.g., psychosis) or a reported childhood learning disability
- Severe aphasia, preventing a participant from understanding the protocol and consent form
- Pre-existing hypoxic pulmonary disease
- Severe hypertension (>160/100)
- Medically documented history of obstructive lung diseases [e.g., Chronic obstructive pulmonary disease (COPD) or significant asthma]
- Ischemic cardiac disease
- Ineligible to undergo MRI or TMS
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Cognitive Effects of Acute Intermittent Hypoxia-Induced Neuroplasticity in Traumatic Brain Injury
This study is designed to answer questions related to safety and preliminary efficacy of Acute Intermittent Hypoxia (AIH) in Traumatic Brain Injury (TBI) survivors. First, we aim to establish whether brief reductions in inhaled oxygen concentration can be safely tolerated in TBI survivors. Second, we aim to establish whether there are any effects of AIH on memory, cognition, and motor control. Participants will be monitored closely for any adverse events during these experiments. Data will be analyzed to determine if there is an improvement in key outcomes at any dose level.
Read the detailed description
The purpose of this study is to determine whether Acute Intermittent Hypoxia (AIH) is safe to administer to medically stable chronic traumatic brain injury (TBI) patients. There is evidence indicating that AIH promotes central nervous system (CNS) neuroplasticity. AIH stimulates oxygen-sensitive serotonergic neurons in the brainstem's raphe nucleus leading to serotonin release into different regions of the CNS. This release leads to activation of serotonin receptors on or near cortical neurons and increased synthesis of multiple trophic factors including brain-derived neurotrophic factor, vascular endothelial growth factor, and erythropoietin. These actions also influence the functioning of neurotransmitters such as GABA. Greater expression of growth factors in the brain facilitates neuroplasticity by increasing synaptic strength, cortical neuron and interneuron excitability, and intra- and inter-brain region connectivity. Of note is that hypoxia-induced neuroplasticity only occurs with acute intermittent exposure, but is not evoked by continuous hypoxia of the same duration. Is AIH safe to administer to TBI patients? The preponderance of prior animal and human evidence suggests that daily episodes of mild AIH do not negatively impact important safety parameters such as resting blood pressure, arterial pressure, heart rate, heart rate variability, cardiac output, or cognitive function. To date, AIH protocols that induce beneficial neuroplasticity without triggering pathological sequelae have been restricted to brief episodes of modest hypoxia with a low cycle number, such as 15 x 90-second episodes of 10% inspired oxygen. Recent studies in humans with chronic spinal cord injury and stroke demonstrated that these modest AIH episodes repeated for five consecutive days can be safely tolerated without pathological consequences. Another recent study showed that even a 4-week protocol of moderate daily AIH (cycling 9%/21% oxygen every 1.5 minutes, 15 cycles per day, for 4 weeks) does not elicit adverse medical consequences or cognitive impairment. Thus, the cumulative evidence suggests that repetitive AIH may be safely used to study whether it can enhance neurobehavioral functioning in TBI patients without deleterious effects. In this study, we will administer mild AIH to 16 patients on four different days spread over the course of two to four weeks, starting with normal oxygen concentration (target SpO2 of 98%) and then progressively reducing the oxygen concentrations over the next three sessions (to 93%, 87%, and 82%). Our primary objective is to determine whether it is safe to administer mild AIH to chronic TBI patients with persistent functional impairments, but who are clinically stable. As a secondary objective in this study, we will assess whether mild AIH administration has any post-session or cumulative effects post-study on memory and cognition, cortical activation as assessed by single-pulse Transcranial Magnetic Stimulation, or whether pre-study brain architecture or functional connectivity as detected by structural and resting-state functional magnetic resonance imaging predicts response to AIH. If no adverse effects to mild AIH are observed in this study, clinical trials using mild AIH alone or in conjunction with neurobehavioral therapies could evaluate whether AIH facilitates the improvement of functional performance after TBI.
- Conditions
- Brain Injuries, Traumatic
- Being tested
- Acute Intermittent Hypoxia
- Keywords
- Hypoxia
- Medical subject headings
- Brain Injuries, Traumatic, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Intermittent HypoxiaProcedure or surgery
Four hypoxia sessions, consisting of 15 cycles of hypoxia (21%, 17%, 13% or 9% O2), each of which lasts up to 60 seconds, interspersed with up to 90-second normoxic episodes.
| Study group | Role | What they receive |
|---|---|---|
| AIH group | Experimental | Hypoxia will be administered via a specialized face mask attached to a gas mixing device (HYP123, Hypoxico Inc.), which controls oxygen content in inhaled air. The hypoxia administering unit will be manually adjusted to supply O2 at the target level for a given session (approximately 21%-normal room air, 17%, 13%, and 9% respectively). Each session will include 15 cycles of hypoxia, each lasting up to 60 seconds, interspersed with up to 90-second normoxic episodes. An oxygen monitor will continuously measure and record the fraction of inspired oxygen delivered (MAX-250E, Maxtec Inc.). Receives: Procedure: Acute Intermittent Hypoxia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Vitals at Visit 2
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Measured: Visit 2 (AIH session #1, 21% O2, sham), conducted 1-6 days after baseline assessment in Visit 1
Change in Vitals at Visit 3
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Measured: Visit 3 (AIH session #2, 17% O2), conducted 1-5 days after Visit 2 (i.e., 2-7 days after baseline)
Change in Vitals at Visit 4
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Measured: Visit 4 (AIH session #3, 13% O2), conducted 1-5 days after Visit 3 (i.e., 6-12 days after baseline)
Change in Vitals at Visit 5
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Measured: Visit 5 (AIH session #4, 9% O2), conducted 2-6 days after Visit 4 (i.e., 8-14 days after baseline)
Change in Symptoms at Visit 2
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Measured: Visit 2 (AIH session #1, 21% O2, sham), conducted 1-6 days after baseline assessment in Visit 1
Change in Symptoms at Visit 3
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Measured: Visit 3 (AIH session #2, 17% O2), conducted 1-5 days after Visit 2 (i.e., 2-7 days after baseline)
Change in Symptoms at Visit 4
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Measured: Visit 4 (AIH session #3, 13% O2), conducted 1-5 days after Visit 3 (i.e., 6-12 days after baseline)
Change in Symptoms at Visit 5
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Measured: Visit 5 (AIH session #4, 9% O2), conducted 2-6 days after Visit 4 (i.e., 8-14 days after baseline)
Secondary outcomes (12)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Scores
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Update consists of twelve subtests that are used to compute Index scores on five cognitive domains, including Immediate Memory, Delayed Memory, Visuospatial/Constructional Abilities, Language, and Attention. Index scores on each domain range between 40 and 160. Lower scores correspond to greater cognitive deficits.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
California Verbal Learning Test (CVLT-II) Scores
The California Verbal Learning Test (CVLT-II) is a multi-trial word learning test that evaluates verbal memory performance. The test measures Immediate Free Recall (possible score range: 0-80), Short-Delay Free Recall (0-16), Short-Delay Cued Recall (0-16), Long-Delay Free Recall (0-16), Long-Delay Cued Recall (0-16), and Long-Delay Recognition (0-16). The score on each subscale represents the number of correct responses. Higher scores indicate better memory.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
D-KEFS (Delis-Kaplan Executive Function System) Verbal Fluency Test Scores
The D-KEFS (Delis-Kaplan Executive Function System) Verbal Fluency Test measures one's ability to retrieve words from memory. The task is to produce as many words as possible that (1) begin with a specific letter (e.g., F,A,S), (2) belong to a certain semantic category (e.g., animal names), or (3) belong to two alternating categories (e.g., fruits and furniture). The scores (range: 0-unlimited) represent the number of correct responses produced in each condition. Higher scores mean better performance on the test.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Serial Reaction Time Task (SRTT) Scores
The Serial Reaction Time Task (SRTT) measures implicit motor learning. Participants press four keyboard keys in sequence in response to cues on the screen. At first, the same ten-key pattern is repeated without participants' awareness. Next, key presses follow a random sequence. The outcome measure is the difference in average reaction time between the random and learned sequences. An increase in reaction time during the random sequence reflects the cognitive effort required to inhibit the previously learned pattern. Therefore, larger differences indicate stronger implicit motor learning.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Trail Making Test (TMT) Scores
The Trail Making Test (TMT) is a measure of motor and executive function. This test has two parts, Part A and Part B. Part A requires participants to draw a line between circles containing numbers in ascending order (e.g., 1-2-3…etc.). Part B requires participants to draw a line, alternating between ascending numbers and letters (e.g., 1-A-2-B…etc.). The outcome measures are the reaction times in seconds required to complete Part A and Part B. Faster reaction times indicate better test performance.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Finger Tapping Test Scores
The Finger Tapping Test measures the rate of finger presses in order to assess simple motor coordination. In this task, participants are asked to tap the lever on a wooden board with their index finger as fast as possible for ten seconds. Five trials with each hand are administered. The first two trials are discarded as practice. The average number of taps on the subsequent three trials are recorded as the test score. Higher scores reflect better motor function.
Measured: baseline (Visit 1) and follow-up (Visit 6, 9-17 days after baseline), as well as one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Grooved Pegboard Test Scores
The Grooved Pegboard Test measures manual dexterity and eye-hand coordination. It consists in inserting grooved pegs into a 5×5 board as quickly as possible, without skipping any slots, starting from the top row. One hand is tested at a time, starting with the dominant one. When using the right hand, participants are asked to fill the board from left to right. When using the left hand, they complete the board from right to left. The outcome measure is the amount of time in seconds required to complete the board. Faster reaction times reflect better motor function.
Measured: baseline (Visit 1) and follow-up (Visit 6, 9-17 days after baseline), as well as one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Rey Auditory Verbal Learning Test (RAVLT) Scores
The Rey Auditory Verbal Learning Test (RAVLT) is a standardized assessment of verbal learning and memory that measures Immediate Free Recall (score range: 0-75), Short-Delay Free Recall (0-15), Long-Delay Free Recall (0-15), and Long-Delay Forced-Choice Recognition (0-15). The scores on each subscale represent the total number of correct responses. Higher scores mean better test performance.
Measured: approximately one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Beck Depression Inventory (BDI-II) Scores
The Beck Depression Inventory (BDI-II) is a 21-item self-report questionnaire assessing the severity of depressive symptoms. Each question has four response options, scored from 0 to 3. The outcome measure is the total score (range: 0-63). Higher scores reflect greater severity of depression symptoms.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Visual Analogue Mood Scale (VAM-S) Scores
The Visual Analogue Mood Scale (VAM-S) consists of a single 100-mm horizontal line representing a scale ranging from "very bad mood" (score: 0) to "very good mood" (score:100). Participants are asked to place a mark on the line corresponding to their current mood. The outcome measure is the length of the segment between the leftmost part of the scale and the mark made by the participant in mm. Higher scores mean better mood.
Measured: approximately one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Motor Evoked Potentials (MEPs)
Transcranial magnetic stimulation (TMS) is delivered to the scalp in order to elicit MEPs in the first dorsal interroseous muscle of the dominant hand. The optimal stimulation site is determined by moving the coil over the scalp in small steps along the hand representation of the primary motor cortex to find the region where the largest MEPs can be evoked in the target muscle with the minimum intensity. Change in MEP amplitudes is used to assess improvement in motor function.
Measured: approximately 45 min after AIH in Visit 2 (1-6 days after baseline) and Visit 5 (8-14 days after baseline)
MRI
MRI was used to determine whether there are changes in brain structure or function from baseline, as assessed by a physician and a neuroimaging data analyst. The outcome measure is the number of participants with observable changes in structural or functional images of the brain following the AIH intervention.
Measured: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start15 Mar 2022
- Primary completion29 Jan 2024
- Study completion29 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain Injuries, TraumaticStudies of the same condition, open and under way.
- More trials run by Shirley Ryan AbilityLabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jordan Grafman, Ph.D, Shirley Ryan AbilityLab
- Investigators
- Jordan Grafman, PhD, Principal investigator, Shirley Ryan AbilityLab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04890639
- Sponsor's protocol ID
- STU00213969
- Other IDs
- 1R21NS114815-01A1
- Acronym
- AIH
- Status last verified
- Dec 2025
- First submitted
- 28 Apr 2021
- Last updated
- 18 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be made available to other researchers when published.
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Cognitive Effects of Acute Intermittent Hypoxia-Induced Neuroplasticity in Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT04890639
- Acronym / sponsor ID
- AIH / STU00213969
- Conditions
- Brain Injuries, Traumatic
- Keywords
- Hypoxia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- 29 Jan 2024 (actual)
- Study completion
- 29 Jan 2024 (actual)
- First posted
- 18 May 2021 (actual)
- Results
- Posted 18 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to answer questions related to safety and preliminary efficacy of Acute Intermittent Hypoxia (AIH) in Traumatic Brain Injury (TBI) survivors. First, we aim to establish whether brief reductions in inhaled oxygen concentration can be safely tolerated in TBI survivors. Second, we aim to establish whether there are any effects of AIH on memory, cognition, and motor control. Participants will be monitored closely for any adverse events during these experiments. Data will be analyzed to determine if there is an improvement in key outcomes at any dose level.
Detailed description
The purpose of this study is to determine whether Acute Intermittent Hypoxia (AIH) is safe to administer to medically stable chronic traumatic brain injury (TBI) patients. There is evidence indicating that AIH promotes central nervous system (CNS) neuroplasticity. AIH stimulates oxygen-sensitive serotonergic neurons in the brainstem's raphe nucleus leading to serotonin release into different regions of the CNS. This release leads to activation of serotonin receptors on or near cortical neurons and increased synthesis of multiple trophic factors including brain-derived neurotrophic factor, vascular endothelial growth factor, and erythropoietin. These actions also influence the functioning of neurotransmitters such as GABA. Greater expression of growth factors in the brain facilitates neuroplasticity by increasing synaptic strength, cortical neuron and interneuron excitability, and intra- and inter-brain region connectivity. Of note is that hypoxia-induced neuroplasticity only occurs with acute intermittent exposure, but is not evoked by continuous hypoxia of the same duration. Is AIH safe to administer to TBI patients? The preponderance of prior animal and human evidence suggests that daily episodes of mild AIH do not negatively impact important safety parameters such as resting blood pressure, arterial pressure, heart rate, heart rate variability, cardiac output, or cognitive function. To date, AIH protocols that induce beneficial neuroplasticity without triggering pathological sequelae have been restricted to brief episodes of modest hypoxia with a low cycle number, such as 15 x 90-second episodes of 10% inspired oxygen. Recent studies in humans with chronic spinal cord injury and stroke demonstrated that these modest AIH episodes repeated for five consecutive days can be safely tolerated without pathological consequences. Another recent study showed that even a 4-week protocol of moderate daily AIH (cycling 9%/21% oxygen every 1.5 minutes, 15 cycles per day, for 4 weeks) does not elicit adverse medical consequences or cognitive impairment. Thus, the cumulative evidence suggests that repetitive AIH may be safely used to study whether it can enhance neurobehavioral functioning in TBI patients without deleterious effects. In this study, we will administer mild AIH to 16 patients on four different days spread over the course of two to four weeks, starting with normal oxygen concentration (target SpO2 of 98%) and then progressively reducing the oxygen concentrations over the next three sessions (to 93%, 87%, and 82%). Our primary objective is to determine whether it is safe to administer mild AIH to chronic TBI patients with persistent functional impairments, but who are clinically stable. As a secondary objective in this study, we will assess whether mild AIH administration has any post-session or cumulative effects post-study on memory and cognition, cortical activation as assessed by single-pulse Transcranial Magnetic Stimulation, or whether pre-study brain architecture or functional connectivity as detected by structural and resting-state functional magnetic resonance imaging predicts response to AIH. If no adverse effects to mild AIH are observed in this study, clinical trials using mild AIH alone or in conjunction with neurobehavioral therapies could evaluate whether AIH facilitates the improvement of functional performance after TBI.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AIH group | Experimental | Procedure: Acute Intermittent HypoxiaHypoxia will be administered via a specialized face mask attached to a gas mixing device (HYP123, Hypoxico Inc.), which controls oxygen content in inhaled air. The hypoxia administering unit will be manually adjusted to supply O2 at the target level for a given session (approximately 21%-normal room air, 17%, 13%, and 9% respectively). Each session will include 15 cycles of hypoxia, each lasting up to 60 seconds, interspersed with up to 90-second normoxic episodes. An oxygen monitor will continuously measure and record the fraction of inspired oxygen delivered (MAX-250E, Maxtec Inc.). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18-65 years
- A first time, mild to moderate traumatic brain injury (TBI) confirmed by medical records
- When available, a Glasgow Coma Scale score between 9-15
- Able to use a keyboard
- Able to understand and communicate in English
Key exclusion criteria (7 listed)
- Other neurological diagnoses or a diagnosis of severe psychiatric disorder (e.g., psychosis) or a reported childhood learning disability
- Severe aphasia, preventing a participant from understanding the protocol and consent form
- Pre-existing hypoxic pulmonary disease
- Severe hypertension (>160/100)
- Medically documented history of obstructive lung diseases [e.g., Chronic obstructive pulmonary disease (COPD) or significant asthma]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute Intermittent HypoxiaFour hypoxia sessions, consisting of 15 cycles of hypoxia (21%, 17%, 13% or 9% O2), each of which lasts up to 60 seconds, interspersed with up to 90-second normoxic episodes. | Procedure or surgery | AIH group |
Primary outcome
Change in Vitals at Visit 2
Time frame: Visit 2 (AIH session #1, 21% O2, sham), conducted 1-6 days after baseline assessment in Visit 1
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Change in Vitals at Visit 3
Time frame: Visit 3 (AIH session #2, 17% O2), conducted 1-5 days after Visit 2 (i.e., 2-7 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Change in Vitals at Visit 4
Time frame: Visit 4 (AIH session #3, 13% O2), conducted 1-5 days after Visit 3 (i.e., 6-12 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Change in Vitals at Visit 5
Time frame: Visit 5 (AIH session #4, 9% O2), conducted 2-6 days after Visit 4 (i.e., 8-14 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by concerning change in blood pressure, SpO2, and heart rate from baseline, as reviewed and determined by the medical monitor.
Change in Symptoms at Visit 2
Time frame: Visit 2 (AIH session #1, 21% O2, sham), conducted 1-6 days after baseline assessment in Visit 1
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Change in Symptoms at Visit 3
Time frame: Visit 3 (AIH session #2, 17% O2), conducted 1-5 days after Visit 2 (i.e., 2-7 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Change in Symptoms at Visit 4
Time frame: Visit 4 (AIH session #3, 13% O2), conducted 1-5 days after Visit 3 (i.e., 6-12 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
Change in Symptoms at Visit 5
Time frame: Visit 5 (AIH session #4, 9% O2), conducted 2-6 days after Visit 4 (i.e., 8-14 days after baseline)
Number of Participants With Treatment-Related Adverse Events as assessed by the presence of "Yes" responses on a verbally-administered 9-item "Yes/No" subjective symptom checklist, as reviewed and determined by the medical monitor. The nine symptoms on this checklist are as follows: 1) chest pain, 2) shortness of breath, 3) lightheadedness, 4) neck pain, 5) dizziness, 6) arm pain (left side for cardiac symptoms), 7) sweatiness/feeling warm, 8) sensory changes (new signs of numbness), 9) increased weakness. Participants will be asked if they are experiencing any of the above symptoms at the 2-minute, 6-minute, 14-minute, 24-minute, and 30-minute timepoints throughout an AIH session.
12 secondary outcomes
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
California Verbal Learning Test (CVLT-II) Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
D-KEFS (Delis-Kaplan Executive Function System) Verbal Fluency Test Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Serial Reaction Time Task (SRTT) Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Trail Making Test (TMT) Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Finger Tapping Test Scores
Time frame: baseline (Visit 1) and follow-up (Visit 6, 9-17 days after baseline), as well as one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Grooved Pegboard Test Scores
Time frame: baseline (Visit 1) and follow-up (Visit 6, 9-17 days after baseline), as well as one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Rey Auditory Verbal Learning Test (RAVLT) Scores
Time frame: approximately one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Beck Depression Inventory (BDI-II) Scores
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Visual Analogue Mood Scale (VAM-S) Scores
Time frame: approximately one hour after AIH in Visit 2 (1-6 days after baseline), Visit 3 (2-7 days after baseline), Visit 4 (6-12 days after baseline) and Visit 5 (8-14 days after baseline)
Motor Evoked Potentials (MEPs)
Time frame: approximately 45 min after AIH in Visit 2 (1-6 days after baseline) and Visit 5 (8-14 days after baseline)
MRI
Time frame: Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD will be made available to other researchers when published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordan Grafman, PhD principal investigator
Shirley Ryan AbilityLab
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute Intermittent Hypoxia in people with Brain Injuries, Traumatic, run by Shirley Ryan AbilityLab at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Vitals at Visit 2 (time frame: Visit 2 (AIH session #1, 21% O2, sham), conducted 1-6 days after baseline assessment in Visit 1). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.