Brain Wave Monitoring for Traumatic Brain Injury

(INDICT Trial)

Overseen By Karmen Herzig

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Cincinnati

Disqualifiers: Non-survivable injury, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Full-band Electrocorticography, Electrocorticography, ECoG, Intracranial EEG, Treatment Algorithm, Ketalar, Special K for traumatic brain injury?

Research suggests that using a variety of monitoring techniques, including brain wave monitoring, can improve outcomes for traumatic brain injury patients by allowing for more personalized care. Although specific drugs or treatments like Ketalar (a form of anesthesia) are not directly proven effective in the studies, the overall strategy of multimodal monitoring is associated with better patient outcomes. ^{1 2 3 4 5}

How is the drug Ketalar (Special K) unique in treating traumatic brain injury?

Ketalar, also known as Special K, is unique because it is primarily used as an anesthetic and has dissociative properties, which means it can alter perception and consciousness. This makes it different from other treatments for traumatic brain injury, which may not have these effects. ^{5 6 7 8 9}

Eligibility Criteria

This trial is for individuals who need emergency surgery (craniotomy) to treat severe traumatic brain injury within 72 hours after the injury. It's not for those with non-survivable injuries, those who've had a certain type of skull surgery due to swelling, are in another TBI study, or are pregnant.

Inclusion Criteria

I need urgent brain surgery within 72 hours after a head injury.

Exclusion Criteria

I had surgery to relieve pressure inside my skull due to a severe brain injury.

Pregnancy

Co-enrollment in another therapeutic TBI trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo intensive care with real-time electrocorticographic monitoring to guide therapy for spreading depolarization suppression

Up to 2 weeks

Continuous monitoring during intensive care

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Periodic assessments

Treatment Details

Interventions

• Full-band Electrocorticography
• Treatment Algorithm

Trial Overview The INDICT study tests if monitoring brain activity with electrocorticography can help guide intensive care treatments aimed at stopping spreading depolarizations—a harmful pattern seen after brain injuries—in patients post-surgery.

Participant Groups

Group I: SD-Guided Care Experimental Treatment 2 Interventions

In this arm, ECoG data will be reviewed for SDs in real-time using the bedside clinical CNS monitor. As a secondary measure, recognition of SDs will be facilitated by custom software on a laptop that receives data from the CNS monitor. Data on SD occurrence will be used to guide treatment in a tier-based therapeutic escalation and de-escalation protocol with the goal of SD suppression. Therapies to be used among the tiers include adjusted targets for MAP, CPP, PaCO2, plasma glucose, temperature, as well as ketamine pharmacotherapy. Changes between tiers are determined by the success or failure of SD suppression at the given treatment level.

Group II: Standard ICU Care Active Control 1 Intervention

Management in the Standard ICU Care arm will follow published national guidelines consisting of common ICU-based targets for physiologic intervention that are thought to mitigate the development of secondary brain injuries. Continuous ECoG monitoring will be performed for seizure monitoring, but information on the course of SDs in these patients will not be used to guide care. To enforce blinding to SD-related ECoG data, the ECoG bedside software will be locked with password protection to prevent displays with frequency filtering and time/amplitude scales that are necessary to identify SDs.

Treatment Algorithm is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Pain management
• Sedation

Approved in European Union as Ketalar for:

• Anesthesia
• Pain management
• Sedation

Approved in Canada as Ketalar for:

• Anesthesia
• Pain management
• Sedation

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

University of New Mexico

Collaborator

Trials

393

Recruited

3,526,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Findings from Research

Current management of traumatic brain injury (TBI) focuses on preventing and treating secondary brain damage rather than relying solely on pharmacological agents, which have shown limited success in clinical settings.

Recent studies indicate that using multimodal monitoring techniques to guide TBI treatment can lead to better patient outcomes by allowing for personalized care based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological monitoring of the severe traumatic brain injury patient in the intensive care unit. Le Roux, P.[2022]

Multimodal monitoring tools, both invasive and noninvasive, are essential for managing critically ill patients with traumatic brain injury, as they help prevent secondary brain injury.

Over the past 20 years, there has been significant advancement in monitoring techniques, including intracranial pressure, blood flow, metabolism, and oxygenation, which are crucial for understanding and managing brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in cerebral monitoring for the patient with traumatic brain injury. Mahdavi, Z., Pierre-Louis, N., Ho, TT., et al.[2017]

Long-term scalp EEG monitoring in 60 patients with acute severe traumatic brain injury (TBI) provides valuable insights into prognosis, with specific EEG features indicating a higher risk of unfavorable outcomes, such as background rhythm slowing and absence of reactivity.

The study found that certain EEG patterns, like rhythmic and periodic patterns, are strongly associated with non-convulsive status epilepticus (NCSE), suggesting that EEG monitoring can help in diagnosing this condition, although NCSE itself does not necessarily predict a poor outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term EEG monitoring in patients with acute traumatic brain injury]. Sinkin, MV., Talypov, AE., Yakovlev, AA., et al.[2021]

The management of head injury focuses on preventing secondary brain damage by addressing issues like raised intracranial pressure and ensuring adequate blood flow to the brain, which is crucial for improving patient outcomes.

Despite advancements in understanding the mechanisms of brain injury and the development of neuroprotective agents, there is still a lack of strong evidence supporting many treatment methods, highlighting the need for improved guidelines and monitoring techniques in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for neurotrauma. Maas, AI., Dearden, M., Servadei, F., et al.[2019]

The QEEG algorithm demonstrated high sensitivity (92.45%) and specificity (90.00%) in distinguishing patients with traumatic brain injury (TBI) who required a CT scan from those who did not, based on EEG data from 105 patients.

The TBI discriminant index, which showed significant differences between CT+ patients (mean index of 80.4) and controls (24.5), could enhance triage decisions in the Emergency Department by indicating when a CT scan is necessary for patients with altered mental status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of brain electrical activity to quantify traumatic brain injury in the emergency department. Naunheim, RS., Treaster, M., English, J., et al.[2019]

A new algorithm has been developed to effectively detect and track rhythmic patterns in EEG signals, which is crucial for monitoring brain activity in patients.

The algorithm successfully tracked the alpha rhythm in critically ill patients sedated with midazolam, indicating its potential utility in clinical settings for assessing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracking rhythm in long-term EEG recordings using empirical mode calculation. Lipping, T., Anier, A., Ratsep, I., et al.[2020]

The new depth of anesthesia (DoA) monitoring index effectively tracks the transition from consciousness to unconsciousness during anesthesia induction in real time, indicating its potential for improving patient safety.

The method enhances raw EEG data by removing noise and adjusting window lengths, which may lead to more accurate and reliable monitoring of anesthesia depth compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring and reflecting depth of anesthesia using wavelet and power spectral density. Nguyen-Ky, T., Wen, PP., Li, Y., et al.[2011]

The paper highlights the limitations of traditional Fast Fourier Transforms (FFTs) in analyzing EEG signals, particularly issues with resolution and leakage effects, and introduces an auto-regressive (AR) modeling approach to improve spectral estimation.

It also presents advanced algorithms, including adaptive AR parameter estimation and wavelet-based time-frequency representation, which are particularly effective for analyzing transient or rapidly changing neurological signals, as demonstrated through EEG data from animals experiencing hypoxic asphyxic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spectral analysis methods for neurological signals. Muthuswamy, J., Thakor, NV.[2019]

A mathematical analysis of 80 electroencephalograms (EEGs) from 20 patients with severe brain injuries revealed significant disturbances in the frequency spectrum, which can aid in diagnosis during acute care.

The study introduced an adaptive filtration system to assess spectral density, enhancing the ability to identify specific EEG patterns that are crucial for differentiating types of brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Spectral analysis of the EEG in patients with cerebral contusions and traumatic intracranial hematomas]. Pishel', IaV., Khobta, VD., Kozhukhar', LS.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

Physiological monitoring of the severe traumatic brain injury patient in the intensive care unit. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Advances in cerebral monitoring for the patient with traumatic brain injury. [2017]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Long-term EEG monitoring in patients with acute traumatic brain injury]. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Current recommendations for neurotrauma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Use of brain electrical activity to quantify traumatic brain injury in the emergency department. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Tracking rhythm in long-term EEG recordings using empirical mode calculation. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Measuring and reflecting depth of anesthesia using wavelet and power spectral density. [2011]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Spectral analysis methods for neurological signals. [2019]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Spectral analysis of the EEG in patients with cerebral contusions and traumatic intracranial hematomas]. [2006]