Remote Ischemic Conditioning as a Treatment for Traumatic Brain Injury

Summary

The prevention of secondary brain injury is a primary goal in treating patients with severe traumatic brain injury (TBI). Secondary brain injury results from tissue ischemia induced by increased vascular resistance in the at-risk brain tissue due to compression by traumatic hematomas, and development of cytotoxic and vasogenic tissue edema. While traumatic hematomas may be managed surgically, cytotoxic and vasogenic edema with resulting perfusion impairment perpetuates brain ischemia and injury. Animal models suggest that remote ischemic conditioning (RIC) can reverse these effects and improve perfusion. Based on these findings it is hypothesized that RIC will exert beneficial effects on TBI in man, thereby representing a new therapeutic strategy for severe TBI.

Patients presenting to our institution suffering from severe TBI will be considered for enrollment. Eligible patients will have sustained a blunt, severe TBI (defined by Glasgow Coma Scale \<8) with associated intra-cranial hematoma(s) not requiring immediate surgical decompression, with admission to an intensive care unit and insertion of an intra-cranial pressure monitor. Patients will be randomized to RIC versus sham-RIC intervention cohorts. RIC interventions will be performed using an automated device on the upper extremity delivering 20 cumulative minutes of limb ischemia in a single treatment session. The planned enrollment is a cohort of 40 patients.

Outcomes of this study will include multiple domains. Our primary outcome will include serial assessments of validated serum biomarkers of neuronal injury and systemic inflammation. Secondary outcomes will include descriptions of the clinical course of each patient, radiologic assessment of brain perfusion, and neurocognitive and psychological assessment post-discharge.

If clinical outcomes are improved using RIC, this study would support RIC as a novel treatment for TBI. Its advantages include safety and simplicity and, requiring no specialized equipment, its ability to be used in any environment including pre-hospital settings or in austere theatres. The investigators anticipate that TBI patients treated with RIC will have improved clinical, biochemical, and neuropsychological outcomes compared to standard treatment protocols.

Conditions

• Traumatic Brain Injury
• Trauma, Nervous System
• Reperfusion Injury
• Ischemia, Brain

Interventions

DEVICE

CellAegis Technologies autoRIC device

The autoRIC device from CellAegis technologies will be applied as per the manufacturer's instructions on an upper extremity. The device will automatically inflate and deflate a blood pressure cuff to supra-systolic blood pressures, maintaining an occlusive pressure for a period of five minutes, followed by five minutes of re-perfusion with cuff deflation, completing a ten minute cycle. This cycle will repeat four times for a cumulative total of twenty minutes of occlusive conditioning over forty minutes of intervention time.

OTHER

Best Practice Management of Traumatic Brain Injury

Standard treatment of TBI in a dedicated trauma-neuro intensive care unit will include a tiered management strategy corresponding to many published treatment algorithms, including the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) guidelines for the management of intra-cranial hypertension. Standard practice without limitations will be applied to both cohorts of patients in this study.

Sponsors & Collaborators

• Defence Research and Development Canada

  collaborator INDUSTRY

• Unity Health Toronto

  lead OTHER

Principal Investigators

• Ori D Rotstein, MD · Unity Health Toronto - St. Michael's hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-03

Primary Completion

2023-11-01

Completion

2024-03-03

Countries

• Canada

Study Locations