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

Hyperbaric Oxygen Therapy in Acute Ischemic Stroke Recovery

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Device: Hyperbaric Oxygen Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lawrence Matarutse; Phone Number: 504-962-6419; Email: Lawrence.Matarutse@lcmchealth.org
• Study Contact Backup: Name: Sheryl Martin-Schild, MD, PhD; Phone Number: 504-982-3278; Email: sheryl.martin-schild@lcmchealth.org

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Touro Infirmary New Orleans
      • Contact: Lawrence Matarutse; Phone Number: 504-962-6419; Email: Lawrence.Matarutse@lcmchealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100% oxygen under 2.0ATA; 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; Hyperbaric Oxygen Therapy
Active Comparator: 21% oxygen under 2.0ATA; 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; Hyperbaric Oxygen Therapy
Sham Comparator: 21% oxygen under 1.14ATA; 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; Hyperbaric Oxygen Therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: LCMC Health

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 22, 2023
• First Submitted That Met QC Criteria: November 19, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: Pro00061930.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data requests may be submitted 12 months after publication of all planned manuscripts. Data will be made accessible for up to 12 months. Extensions may be considered on a case-by-case basis. Only fully de-identified data elements will be shared with qualified investigators, for use of personal (non-commercial) research. Data will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
• IPD Sharing Time Frame: Data requests may be submitted 12 months after publication of all planned manuscripts. Data will be made accessible for up to 12 months. Extensions may be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Only fully de-identified data elements will be shared with qualified investigators, for use of personal (non-commercial) research. Data will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No