Trial Outcomes & Findings for Acute Intermittent Hypoxia in Traumatic Brain Injury (NCT NCT04890639)

Participants were recruited through physician referrals, outreach via research registries, flyers and online ads distributed within the Shirley Ryan AbilityLab and other Northwestern-affiliated hospitals. Twelve participants were enrolled into the study between March 2022 and January 2024.

All participants underwent the same treatment protocol.

Acute Intermittent Hypoxia in Traumatic Brain Injury

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.