Acute Intermittent Hypoxia in Traumatic Brain Injury

NCT04890639 | Completed Results

• 2 other identifiers: STU002139691R21NS114815-01A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Brain Injuries, Traumatic

Keywords

Hypoxia

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)

• California Verbal Learning Test (CVLT-II) Scores

  Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)

• D-KEFS (Delis-Kaplan Executive Function System) Verbal Fluency Test Scores

  Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)

• Serial Reaction Time Task (SRTT) Scores

  Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)

• Trail Making Test (TMT) Scores

  Visit 1 (baseline) and Visit 6 (i.e., 9-17 days after baseline)

Study Arms (1)

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.).

Procedure: Acute Intermittent Hypoxia

Interventions

Acute Intermittent Hypoxia PROCEDURE

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.

AIH group

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Hypoxia

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Data from the Rey Auditory Verbal Learning Test administered in Visits 2 through 5 were excluded from the analysis due to significant ceiling effects - the same word list was used across all four sessions, leading to substantial long-term memory contamination, precluding reliable estimation of within-session learning trajectories.

Results Point of Contact

• Title: Ekaterina Delikishkina, Ph.D.
• Organization: Shirley Ryan AbilityLab

kdelikishk@sralab.org

312-238-4579

Study Officials

• Jordan Grafman, PhD

  Shirley Ryan AbilityLab

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 18, 2021
• Study Start: March 15, 2022
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: February 18, 2026
• Results First Posted: February 18, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IDP will become available when published, starting 6 months after publication.
• Access Criteria: Requests to access IPD can be emailed to the P.I., who will review requests on a case-by-case basis.

Locations

US (1)