Hyperbaric Oxygen Therapy in Acute Ischemic Stroke Ischemic Stroke Recovery (Pro00061930)

Study Overview
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Brief Summary
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This study will critically examine the feasibility, safety and efficacy of HBOT during inpatient rehabilitation (IPR) after acute ischemic stroke measured by non-disruption of 3 hours of daily therapy, frequency of neurological deterioration or complications (seizure, hemorrhage, brain edema), and functional communication, activities of daily living (ADLs) and mobility.

Detailed Description
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Preclinical studies support that HBOT augments several adaptive mechanisms following ischemic stroke, including neuroplasticity, cerebral angiogenesis, and regeneration of nerve fibers. The earlier the treatment, the greater potential for a therapeutic effect. However, logistical issues and safety concerns have prevented application of HBOT in the hyperacute window, particularly when coupled with recanalization therapy as the risk of hemorrhagic conversion is highest, monitoring intervals are short, and the natural history is being altered by another treatment. By enrolling patients who are in the subacute phase of stroke who are admitted to an inpatient rehab facility, the risk of HBOT is lower, monitoring intervals are longer, and the selected population has newly acquired and targetable stroke-related disability. Further, the patients are in a supervised setting and available for daily one-hour treatments without disrupting their intensive multidisciplinary rehab plan thereby minimizing nonadherence to daily treatments. Neuroimaging supports that injured, but not dead, brain cells can persist for months after an ischemic event. Hypoxia mediates cellular activity and death through multiple mechanisms. Ongoing decrease in oxygenation to the damaged area due to impaired blood flow works against cellular repair, recovery, and development of new synaptic connections. Increasing oxygen availability has been considered as an obvious treatment for stroke. HBOT has the potential to facilitate the recovery of injured or inactive neurons through increased blood flow and oxygen delivery.

Official Title
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Hyperbaric Oxygen Therapy in Acute Ischemic Stroke Recovery

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Device: Hyperbaric Oxygen Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and above Ischemic stroke proven on neuroimaging Within 7-30 days post-stroke on day 1 of treatment Admitted to Touro Inpatient Rehab Facility Exclusion Criteria: Pre-stroke modified Rankin Scale Score >2 Parenchymal hemorrhagic transformation (PH1 or PH2) Receptive aphasia such that recommendations for preventative measures to mitigate barotrauma cannot be followed History of recurrent and unprovoked seizures requiring a change in management in the last 3 months to control seizures Pulmonary disease requiring supplemental oxygen or daily respiratory medication management (metered dose inhalers, nebulized treatment or steroids)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100% oxygen under 2.0ATA<br>The first intervention arm consists of ischemic stroke patients who would undergo HBOT at 2.0 ATA with 100% oxygenation for 60 minutes x10 treatments (Monday-Friday of two sequential weeks). | Device: Hyperbaric Oxygen Therapy<br>* Hyperbaric Oxygen Therapy<br>|
| Active Comparator: 21% oxygen under 2.0ATA<br>The second intervention arm would consist of ischemic stroke patients undergoing HBOT at 2.0 ATA with 21% oxygen (room air) for 60 minutes x10 treatments (Monday-Friday of two sequential weeks). | Device: Hyperbaric Oxygen Therapy<br>* Hyperbaric Oxygen Therapy<br>|
| Sham Comparator: 21% oxygen under 1.14ATA<br>For sham-control; ischemic stroke patients will undergo placement in the hyperbaric oxygen chamber for the same duration of time (60 minutes x10 treatments, Monday-Friday of two sequential weeks) and pressure maintained at 1.14 ATA with 21% oxygen (room air), a non-therapeutic dose of HBOT that sufficiently increases pressure to simulate ear popping, hence maintaining participants blinded to the intervention / sham. | Device: Hyperbaric Oxygen Therapy<br>* Hyperbaric Oxygen Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy outcome; change in total and subcomponents of functional independence measure (FIM) | Difference in the total, motor, and cognitive functional independence measure (FIM) scores between the three arms at the end of respective treatment blocks (2 - week period). Additional analyses for change in the FIM score will also be conducted. | 2 weeks | 
| Feasibility outcome; proportion of patients who complete HBOT sessions | At least 80% of enrolled patients will be able complete all planned HBOT sessions. HBOT will not directly influence a reduction in quantity or quality of prescribed standard of care rehabilitative therapy. | 2 weeks | 
| Safety outcome 1; ear pain | Mild to moderate ear pain: absolute difference (AD) vs. control group ≤ 20%. | 2 weeks | 
| Safety outcome 2; barotrauma | Barotrauma as diagnosed by clinical exam: AD vs. control group ≤ 10%. | 2 weeks | 
| Safety outcome 3; any other serious adverse event | any of the following absolute difference (AD) vs. control group ≤ 20%: neurological worsening (increase in NIHSS at least 4 points), symptomatic intracranial hemorrhage (parenchymal hemorrhage with neurological worsening), status epilepticus, pulmonary dysfunction (Defined as: respiratory sx requiring supplemental O2, breathing treatment, or evident of pneumothorax or pneumonia on chest imaging performed to evaluate respiratory sx), or death attributed to intervention. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-protocol analysis; change in total and subcomponents of functional independence | Per-protocol analysis comparing total and sub-component FIM scores among HBOT treated and non-HBOT treated patients who completed all HBOT treatment as per the study protocol. Comparison of FIM sub-scores on the FIM functional and cognitive sub-scales. Adjusted estimates of effect of HBOT treatment after controlling for stroke severity (NIHSS), age, pre-morbid mRS evaluated via generalized linear modeling Sub-group analyses for age, sex, race, stroke severity (NIHSS), stroke etiology (TOAST criteria), cortical vs. sub-cortical strokes, pre-morbid disability (pre-morbid mRS) | 2 weeks | 
| Adjusted HBOT treatment effect | Adjusted estimates of effect of HBOT treatment after controlling for stroke severity (NIHSS), age, pre-morbid mRS evaluated via generalized linear modeling | 2 weeks | 
| Sub group analyses to evaluate heterogeneity of treatment effect | Sub-group analyses for age, sex, race, stroke severity (NIHSS), stroke etiology (TOAST criteria), cortical vs. sub-cortical strokes, pre-morbid disability (pre-morbid mRS) | 2 weeks | 
| Long-term outcome; 90-day good functional outcome vs. significant to severe disability or death | We will compare the proportions of HBOT and non-HBOT treated patients who achieve a 90-day mRS of 0 - 2 (good functional outcome) vs. 3 - 6 (Significant to severe disability or death - SSD) based on intent to treat populations. Additional analyses for the 90-day mRS would include Per-protocol analysis comparing 90-day mRS among HBOT treated and non-HBOT treated patients who completed all HBOT treatments as per the study protocol. | 90 days | 
| Long-term outcome; 90-day functional outcome evaluated as ordinal shift in the modified Rankin Scale | Ordinal shift in 90-Day mRS across the full scale of mRS for HBOT treated patients vs. non-HBOT treated patients - based on intent to treat and per protocol populations. | 90 days | 
| Long-term outcome; Adjusted 90-day good functional outcome vs. significant to severe disability or death | Adjusted estimates of effect of HBOT treatment after controlling for stroke severity (NIHSS), age, pre-morbid mRS evaluated via logistic regression - based on intent to treat and per protocol populations. | 90 days | 
| Long-term outcome; Adjusted 90-day functional outcome evaluated as ordinal shirt in the modified Rankin Scale | Adjusted estimates of effect of HBOT treatment after controlling for stroke severity (NIHSS), age, pre-morbid mRS evaluated via ordinal regression models for proportional differences between treated and non-treated patients - based on intent to treat and per protocol populations. | 90 days | 
| Long-term outcome; Sub group analyses to evaluate heterogeneity of treatment effect for 90-day outcome | Sub-group analyses for age, sex, race, stroke severity (NIHSS), stroke etiology (TOAST criteria), cortical vs. sub-cortical strokes, pre-morbid disability (pre-morbid mRS) | 90 days |