An interventional study of Acute Intermittent Hypoxia (AIH) in Stroke, sponsored by Shirley Ryan AbilityLab. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-07.
Sponsored by Shirley Ryan AbilityLab · Not applicable, Interventional, and Treatment
Of the 795,000 people who experience a stroke every year in the US, only a small percentage will achieve full recovery. While current therapies promote strength and endurance, none directly address the unique potential of the brain to reorganize following injury. The goal of this project is to explore the effects of a novel therapy, acute intermittent hypoxia (AIH). During this therapy, individuals receive brief bouts of reduced oxygen levels by inhalation through a face mask. (This is akin to being on top of a tall mountain). In brief exposures, AIH is known to trigger the release of specific proteins that help the brain adapt to oxygen reductions. Published results in people with incomplete spinal cord injury have shown that AIH enhances muscle strength and coordination rather quickly. The research team aims to study the effects of AIH in stroke survivors.
Stroke is the second leading cause of death and a leading cause of long-term disability worldwide. Despite the spontaneous recovery that occurs following a hemispheric stroke, more than half of stroke patients show substantial residual impairments, imposing a significant human and economic burden. This burden is likely to increase in coming decades, due to a rapidly aging population, and the associated progression of cardiovascular risk factors. Accordingly, new interventions to alleviate impairment in stroke survivors are urgently needed. The development and testing of one such novel intervention, termed Acute Intermittent Hypoxia (AIH), is the primary focus of this AHA Innovative Project Award.
The aim is to answer questions related to safety and preliminary efficacy of AIH in stroke survivors. First, the Investigators will establish whether brief reductions in inhaled oxygen concentration can be safely tolerated in stroke survivors. A clinician will closely monitor subjects for any adverse events.
The second aim is to establish the effects of AIH on elbow flexion/extension strength, and on hand grip and pinch strength. Subjects 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.
7,286 studies on the registry are indexed under Stroke; 2,007 are open to participants now.
This study's enrollment of 16 is below the median of 50 across 5,369 interventional studies indexed under Stroke.
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Age ≥18 years;
A first time, unilateral, ischemic, hemispheric stroke, confirmed by magnetic resonance imaging (MRI);
Chedoke assessment > 3
Ability to open and close affected hand
Able to understand and communicate in English
Be able to consent independently
≥ 6 months post stroke
Must have a hemoglobin level above 10g/dl (to be confirmed using handheld noninvasive lab equipment)
Must have ability to attend research visits with a companion for assistance
WOCBP must be comfortable confirming negative pregnancy prior to hypoxia experimental therapy.
Exclusion criteria:
Brain stem or cerebellar stroke; mean Fazekas score rated on initial fluid-attenuated inversion recovery MRI ≥3
Severe aphasia, preventing subject from understanding the protocol and giving written consent;
History of prior neurological disorder;
Pre-existing hypoxic pulmonary disease,
Severe hypertension (>160/100)
Ischemic cardiac disease.
During each session, study participants will receive a single sequence of AIH, consisting of 15 x 60-seconds periods of hypoxia alternating with 90-seconds of normoxia (21% O2), for a total of 30 minutes, whilst in a seated upright position. AIH will be applied by directing gas flow to a reservoir bag connected via plastic tubing to a non re-breathing facemask/respiratory valve system while the participants are in a seated position. Defined gas mixtures will be delivered by manual adjustment of one-way valves attached to a hypoxia generator.
Other: Acute Intermittent Hypoxia (AIH)
An oxygen monitor will continuously measure and record the fraction of inspired oxygen delivered to the subject. Inspired fraction of oxygen (FiO2) of the gas mixture will be individually adjusted using the valve settings to reach the targeted SpO2. The gas mixtures administered during the four sessions will be 21% O2 (target SpO2 = 95%), 17% O2 (target SpO2 = 92%), 13% O2 (target SpO2 = 87%) and 9% O2 (target SpO2 = 82%).
Number of Participants With Adverse Events
All adverse events will be reviewed for safety and study continuation by the medical monitor.
Time frame: 6 days
National Institute of Health Stroke Scale (NIHSS)
is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score ranging from 0-44. A change from baseline to follow up 1 (day 6) is reported, calculated from: value at day 6 - value at baseline
Time frame: Baseline and Day 6
Fugl- Meyer Assessment
Each test element will be graded on a 3-point ordinal scale and summed up to provide a maximum upper limb score of 66. Reliability and validity have been demonstrated. The FMA will be administered while the subject is seated. A score of 0 indicates no upper extremity function or reflexes, a score of 66 indicates complete control of the paretic upper extremity. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
Modified Ashworth Scale
This scale allows for characterization of increases in muscle tone, from low or normal tone to complete limb rigidity. Specifically, we will evaluate the elbow flexors, bilaterally. A score of zero indicates no residual muscle spasticity, a score of 4 is a completely rigid limb with no possible movement. Each participant had their stroke affected elbow joint tested. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
Grip Strength
A dynamometer measures maximum gross grasp (lb.) averaged over three attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. Completed bilaterally, if possible The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
Pinch Strength
Hydraulic Handheld Dynamometer): A dynamometer measures maximum gross grasp (lb.) averaged over 3 attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
Elbow Strength
monitoring changes in isometric elbow flexion force using a dynamometer. A total of three trials will be taken on each side, with a rest break between trials. The average of the three trials will be recorded. Strength recorded in lbs, with a minimum value of zero. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
D-KEFS Color-Word Interference Test
A neuropsychological measure that seeks to evaluate attention and inhibition. Subjects will be asked to read words or name ink colors as quickly as possible within a given time limit. The test supplies the examiner with three separate scores, including an ability to calculate an interference score. This final score allows for interpretation of cognitive flexibility, creativity and cognitive stress. This measure will be utilized to monitor subjects throughout their participation at specific time-points. Audio recording may be taken to ensure accurate recording of responses. The scale is from 1-18, with 10 being at expected level,. A score below 10 is worse performance than expected, and a score above 10 is greater than expected level. The score reported here is the change in score between Day 6 and baseline The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
Time frame: Baseline, Day 6
5 Minute Neurological Test
Quick short tests to assess clinical status performed by physician to ensure no change in neurologic status, The values reported are the count of participants who were found to have no change in neurolgical status from baseline to day 6 by the clinician
Time frame: Baseline, day 6
| Milestone | Hypoxia |
|---|---|
| Started | 16 |
| Completed | 12 |
| Not completed | 4 |
| Withdrew: Withdrawal by subject | 2 |
| Withdrew: Physician decision | 2 |
| Milestone | Hypoxia |
|---|---|
| Started | 12 |
| Completed | 10 |
| Not completed | 2 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Physician decision | 1 |
All adverse events will be reviewed for safety and study continuation by the medical monitor.
| Participants | Hypoxia |
|---|---|
| Elevated blood pressure at baseline — Participants with this adverse event | 1 |
| Elevated blood pressure at baseline — Participants without this adverse event | 11 |
| Heart Rate below 50 beats per minute at baseline — Participants with this adverse event | 2 |
| Heart Rate below 50 beats per minute at baseline — Participants without this adverse event | 10 |
| Claustrophobia — Participants with this adverse event | 1 |
| Claustrophobia — Participants without this adverse event | 11 |
is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score ranging from 0-44. A change from baseline to follow up 1 (day 6) is reported, calculated from: value at day 6 - value at baseline
| Change in score on scale | Hypoxia |
|---|---|
| National Institute of Health Stroke Scale (NIHSS) | -0.3 ± 1.9 |
Each test element will be graded on a 3-point ordinal scale and summed up to provide a maximum upper limb score of 66. Reliability and validity have been demonstrated. The FMA will be administered while the subject is seated. A score of 0 indicates no upper extremity function or reflexes, a score of 66 indicates complete control of the paretic upper extremity. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in score on a scale | Hypoxia |
|---|---|
| Fugl- Meyer Assessment | -1.6 ± 4.7 |
This scale allows for characterization of increases in muscle tone, from low or normal tone to complete limb rigidity. Specifically, we will evaluate the elbow flexors, bilaterally. A score of zero indicates no residual muscle spasticity, a score of 4 is a completely rigid limb with no possible movement. Each participant had their stroke affected elbow joint tested. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in score on a scale | Hypoxia |
|---|---|
| Modified Ashworth Scale | -0.1 ± 0.7 |
A dynamometer measures maximum gross grasp (lb.) averaged over three attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. Completed bilaterally, if possible The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in Pounds | Hypoxia |
|---|---|
| Affected Hand | 4.38 ± 7.6 |
| Less Affected Hand | 1.6 ± 10.8 |
Hydraulic Handheld Dynamometer): A dynamometer measures maximum gross grasp (lb.) averaged over 3 attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in Pounds | Hypoxia |
|---|---|
| Affected Hand | 1.7 ± 3.5 |
| Less Affected Hand | 2.1 ± 3.2 |
monitoring changes in isometric elbow flexion force using a dynamometer. A total of three trials will be taken on each side, with a rest break between trials. The average of the three trials will be recorded. Strength recorded in lbs, with a minimum value of zero. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in Pounds | Hypoxia |
|---|---|
| Affected Arm | 7.9 ± 10.4 |
| Less Affected Arm | 8.3 ± 14.4 |
A neuropsychological measure that seeks to evaluate attention and inhibition. Subjects will be asked to read words or name ink colors as quickly as possible within a given time limit. The test supplies the examiner with three separate scores, including an ability to calculate an interference score. This final score allows for interpretation of cognitive flexibility, creativity and cognitive stress. This measure will be utilized to monitor subjects throughout their participation at specific time-points. Audio recording may be taken to ensure accurate recording of responses. The scale is from 1-18, with 10 being at expected level,. A score below 10 is worse performance than expected, and a score above 10 is greater than expected level. The score reported here is the change in score between Day 6 and baseline The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline
| Change in score on a scale | Hypoxia |
|---|---|
| D-KEFS Color-Word Interference Test | -0.1 ± 1.9 |
Quick short tests to assess clinical status performed by physician to ensure no change in neurologic status, The values reported are the count of participants who were found to have no change in neurolgical status from baseline to day 6 by the clinician
| Participants | Hypoxia |
|---|---|
| 5 Minute Neurological Test | 10 |
Collected over Adverse events were collected over the duration of intervention as well as at the single follow up which was within 1 week of interventions */8all occurred at 1 week or less**. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Hypoxia | 0/16 (0%) | 0/16 (0%) | 4/16 (25%) |
| Event | Hypoxia |
|---|---|
| Baseline BradycardiaCardiac disorders | 2/16 |
| Baseline Elevated Blood pressureCardiac disorders | 1/16 |
| ClaustrophobiaGeneral disorders | 1/16 |
| Age, Continuous(years) | Hypoxia |
|---|---|
| Mean | 59.75 ± 6.4 |
| Sex: Female, Male(Participants) | Hypoxia |
|---|---|
| Female | 2 |
| Male | 10 |
| Ethnicity (NIH/OMB)(Participants) | Hypoxia |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 12 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Hypoxia |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 9 |
| White | 3 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Hypoxia |
|---|---|
| United States | 12 |
| Chedoke McMaster Hand Score(units on a scale) | Hypoxia |
|---|---|
| Mean | 4.5 ± 1.83 |
| Time since Stroke Onset(years) | Hypoxia |
|---|---|
| Mean | 9.03 ± 7.16 |
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