StrokeNCT04019522
American Heart Association- Stroke/Hypoxia Study
A study testing Acute Intermittent Hypoxia (AIH) in people with Stroke, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Acute Intermittent Hypoxia (AIH)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2019to 1 Jul 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- ≥ 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Exploration of Acute Intermittent Hypoxia as a Tool to Enhance Neural Recovery in Stroke Survivors; a Pilot Safety Study.
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.
Read the detailed description
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.
- Conditions
- Stroke
- Being tested
- Acute Intermittent Hypoxia (AIH)
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Intermittent Hypoxia (AIH)Other
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%).
| Study group | Role | What they receive |
|---|---|---|
| Hypoxia | Experimental | 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. Receives: Other: Acute Intermittent Hypoxia (AIH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
All adverse events will be reviewed for safety and study continuation by the medical monitor.
Measured: 6 days
Secondary outcomes (8)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline, day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2019
- Study start15 Jul 2019
- Primary completion1 Feb 2022
- Study completion1 Jul 2025
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zev Rymer, Shirley Ryan AbilityLab
- Investigators
- Zev Rymer, MD/PhD, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04019522
- Sponsor's protocol ID
- STU: 00208610
- Status last verified
- Mar 2026
- First submitted
- 19 Jun 2019
- Last updated
- 7 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pearcey GEP, Barry AJ, Sandhu MS, Carroll TJ, Roth EJ, Rymer WZ. Acute Intermittent Hypoxia in People Living With Chronic Stroke: A Case Series. Stroke. 2025 Apr;56(4):1054-1057. doi: 10.1161/STROKEAHA.124.046620. Epub 2025 Feb 25.
PubMed 39996325
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploration of Acute Intermittent Hypoxia as a Tool to Enhance Neural Recovery in Stroke Survivors; a Pilot Safety Study.
- ClinicalTrials.gov ID
- NCT04019522
- Acronym / sponsor ID
- STU: 00208610
- Conditions
- Stroke
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 15 Jul 2019 (actual)
- Results
- Posted 7 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hypoxia | Experimental | Other: Acute Intermittent Hypoxia (AIH)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
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 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%). | Other | Hypoxia |
Primary outcome
Number of Participants With Adverse Events
Time frame: 6 days
All adverse events will be reviewed for safety and study continuation by the medical monitor.
8 secondary outcomes
National Institute of Health Stroke Scale (NIHSS)
Time frame: Baseline and Day 6
Fugl- Meyer Assessment
Time frame: Baseline, Day 6
Modified Ashworth Scale
Time frame: Baseline, Day 6
Grip Strength
Time frame: Baseline, Day 6
Pinch Strength
Time frame: Baseline, Day 6
Elbow Strength
Time frame: Baseline, Day 6
D-KEFS Color-Word Interference Test
Time frame: Baseline, Day 6
5 Minute Neurological Test
Time frame: Baseline, day 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39996325Pearcey GEP, Barry AJ, Sandhu MS, Carroll TJ, Roth EJ, Rymer WZ. Acute Intermittent Hypoxia in People Living With Chronic Stroke: A Case Series. Stroke. 2025 Apr;56(4):1054-1057. doi: 10.1161/STROKEAHA.124.046620. Epub 2025 Feb 25.
- Individual participant dataSharing planned: No
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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.
Zev Rymer, MD/PhD principal investigator
Principal Investigator
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 (AIH) in people with Stroke, 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 10 inclusion and 6 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 7 Apr 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 7 Apr 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?
Number of Participants With Adverse Events (time frame: 6 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04019522, which also lists 1 linked publication.
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 7 Apr 2026; AzTrials last refreshed its copy on 29 Oct 2026.