Clinical Trials Logo

Clinical Trial Summary

This study is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative treatment of severe traumatic brain injury.


Clinical Trial Description

The goal of acute TBI treatment is to minimize secondary damage that evolves over hours to days after the primary injury. Until now, however, there have been no methods for monitoring heterogeneous pathologic mechanisms to identify patients for appropriate neuroprotection therapies. Using invasive monitoring, investigators have documented that spreading depolarizations (SD), a cytotoxic dysfunction of cerebral gray matter that has been well-characterized through 60 years of research in animal models, are the dominant pathophysiologic process in peri-lesion cortex of many, but not all, severe TBI patients. Furthermore, it was found that the occurrence of SD as a secondary injury process in patients is an independent predictor of worse neurologic outcomes. Thus, monitoring of SD as a heterogeneous mechanism in TBI may allow selective use of therapy in only those patients who might benefit. Here the investigators will conduct a randomized Phase 2 feasibility trial that uses real-time SD monitoring to guide implementation of a tier-based protocol of intensive care therapies aimed at SD suppression. The study is based on the hypothesis that outcomes from severe TBI can be improved by targeting intensive care therapies to suppress the pathology of SDs as a brain marker and mechanism of secondary injury. The objective of this study is to test the feasibility of this approach to intensive care management of severe TBI in a Phase 2 trial that uses real-time SD monitoring to guide administration of prescribed therapies to suppress SD. The aims are to (1) determine the feasibility of real-time SD monitoring to guide intensive care management of severe TBI, and (2) determine the effect of SD-guided vs. standard care management to reduce secondary brain insults in severe TBI. This is a randomized Phase 2 clinical trial enrolling approximately 72 patients at 3 sites. Patients requiring neurological surgery for emergency treatment of TBI will be enrolled. The need for surgery allows for the placement of an electrode strip on the brain during surgery for subsequent electrocorticography (ECoG). ECoG data will be monitored continuously in real-time for the occurrence of SDs during intensive care. When SDs are observed, these patients (~60%, or n=43) will be randomized 1:1 to either standard (control) or SD-guided care. In the standard care arm, treatment will follow local and national guidelines with blinding to further ECoG results. In the SD-guided arm, treatment will follow a tiered-based protocol with escalation and de-escalation based on efficacy to suppress further SD pathology. Treatments will include use of ketamine sedation and adjusted targets for plasma glucose, cerebral perfusion pressure, temperature, and end-tidal CO2. As outcomes, the accuracy of real-time SD scoring and compliance with protocol tier assignment and therapy implementation will be assessed. The burden of SD pathology, other measures of cerebral physiology (intracranial and cerebral perfusion pressures, and brain oxygenation), and medical complications will also be compared between the two study arms. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05337618
Study type Interventional
Source University of Cincinnati
Contact Jed A Hartings, PhD
Phone 513-295-2370
Email jed.hartings@uc.edu
Status Recruiting
Phase Phase 2
Start date December 16, 2022
Completion date September 20, 2026

See also
  Status Clinical Trial Phase
Terminated NCT03052712 - Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies N/A
Recruiting NCT05503316 - The Roll of Balance Confidence in Gait Rehabilitation in Persons With a Lesion of the Central Nervous System N/A
Completed NCT04356963 - Adjunct VR Pain Management in Acute Brain Injury N/A
Completed NCT03418129 - Neuromodulatory Treatments for Pain Management in TBI N/A
Terminated NCT03698747 - Myelin Imaging in Concussed High School Football Players
Recruiting NCT05130658 - Study to Improve Ambulation in Individuals With TBI Using Virtual Reality -Based Treadmill Training N/A
Recruiting NCT04560946 - Personalized, Augmented Cognitive Training (PACT) for Service Members and Veterans With a History of TBI N/A
Completed NCT05160194 - Gaining Real-Life Skills Over the Web N/A
Recruiting NCT02059941 - Managing Severe Traumatic Brain Injury (TBI) Without Intracranial Pressure Monitoring (ICP) Monitoring Guidelines N/A
Recruiting NCT03940443 - Differences in Mortality and Morbidity in Patients Suffering a Time-critical Condition Between GEMS and HEMS
Recruiting NCT03937947 - Traumatic Brain Injury Associated Radiological DVT Incidence and Significance Study
Completed NCT04465019 - Exoskeleton Rehabilitation on TBI
Recruiting NCT04530955 - Transitioning to a Valve-Gated Intrathecal Drug Delivery System (IDDS) N/A
Recruiting NCT03899532 - Remote Ischemic Conditioning in Traumatic Brain Injury N/A
Suspended NCT04244058 - Changes in Glutamatergic Neurotransmission of Severe TBI Patients Early Phase 1
Completed NCT03307070 - Adapted Cognitive Behavioral Treatment for Depression in Patients With Moderate to Severe Traumatic Brain Injury N/A
Recruiting NCT04274777 - The Relationship Between Lipid Peroxidation Products From Traumatic Brain Injury and Secondary Coagulation Disorders
Withdrawn NCT05062148 - Fundamental and Applied Concussion Recovery Modality Research and Development: Applications for the Enhanced Recovery N/A
Withdrawn NCT04199130 - Cognitive Rehabilitation and Brain Activity of Attention-Control Impairment in TBI N/A
Withdrawn NCT03626727 - Evaluation of the Efficacy of Sodium Oxybate (Xyrem®) in Treatment of Post-traumatic Narcolepsy and Post-traumatic Hypersomnia Early Phase 1