Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU

Not Applicable

Recruiting

• Conditions: Consciousness Disorders
• Interventions: Other: Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG

• Registration Number: NCT06568536
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

Disorders of consciousness (DoC) caused by severe brain injury affect millions of people worldwide each year. A patient's level of consciousness in the intensive care unit (ICU) significantly impacts the recovery from disability and is a primary determinant of family decisions about withdrawal of life-sustaining therapy (WLST). However, reliable assessment of consciousness in the ICU remains elusive. Transcranial magnetic stimulation-electroencephalography (TMS-EEG) is a tool that has shown the best performance in detecting signs of consciousness in patients with chronic DoC. The goals of this prospective, observational study are to demonstrate the diagnostic performance and prognostic utility of TMS-EEG in the ICU setting.

Detailed Description

Disorders of consciousness (DoC) caused by severe brain injury affect millions of people worldwide each year. A patient's level of consciousness in the intensive care unit (ICU) significantly influences the recovery from disability and may affect family decisions about withdrawal of life-sustaining therapy (WLST). Transcranial magnetic stimulation-electroencephalography (TMS-EEG) has shown the best performance in detecting signs of consciousness in patients with chronic DoC. The goals of this multi-center observational study are to demonstrate the diagnostic performance and prognostic utility of TMS-EEG in patients with DoC caused by severe brain injuries in the ICU.

Through this research, we aim to demonstrate that:

* TMS-EEG can detect 95% of conscious patients who are defined as conscious by a combination of tests that aim to detect overt and covert consciousness.

* TMS-EEG measurements can predict 6-month outcomes on the Disability Rating Scale (DRS) in patients in an acute vegetative state, controlling for age, Glasgow Coma Scale (GCS) score, and injury mechanism

All participants will undergo repeated behavioral assessments, task-based electroencephalography (EEG), and TMS-EEG. Of note, conventional brain magnetic resonance imaging (MRI) and task-based functional MRI are optional.

Study Timeline

• Study First Submitted: 2024-08-21
• Study First Submitted QC: 2024-08-21
• Study First Posted: 2024-08-23
• Study Start: 2024-11-08
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2029-08
• Study Completion: 2029-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Age greater than or equal to 18
2. Functionally independent at baseline
3. Acquired brain injury within the last 28 days
4. Disorder of consciousness, as defined by no instance of following commands (i.e., Glasgow Coma Scale motor score = 6) on two or more consecutive assessments
5. Continuous intravenous sedation able to be discontinued for at least 10 minutes
6. ICU clinicians approve safe placement of 64-electrode EEG cap on the scalp

Additional inclusion criteria are present in the study protocol.

Exclusion Criteria

1. Status epilepticus or uncontrolled seizure disorder
2. No head CT scan from current hospital admission AND contraindications for MRI: conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments)
3. Medical instability, restlessness, or other factors identified by the PI that would either prevent safe participation or compromise data acquisition
4. Hemicraniectomy

If a subject meets a contraindication for MR imaging, the subject may participate in all other aspects of the study except MRI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with acute disorders of consciousness receiving TMS-EEG	Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG	Adults with acute severe traumatic brain injury who undergo advanced neuroimaging and electrophysiological studies while in the intensive care unit and are followed for 6 months post-injury.

Primary Outcome Measures

Name	Time	Method
Presence of consciousness as defined by a composite reference standard for consciousness that combines behavior, task-based EEG, and task-based fMRI	48 hours after the end of the TMS-EEG assessment	Behavioral assessments of consciousness (up to 5): The CRS-R consists of 6 subscales designed to assess auditory function, receptive and expressive language, visuoperception, communication ability, motor functions, and arousal level. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best). The CRSR-FAST assesses only those CRS-R behaviors that differentiate conscious (i.e., MCS) from unconscious (i.e., coma/VS) patients.; Functional assessments of covert consciousness: A participant is classified as being conscious on task-based EEG if the probability with which the classifier distinguished task from rest conditions is p \< 0.05 and the accuracy value that indicates the classifier's performance is ≥ 60%. A participant is classified as being conscious on task-based fMRI if there is one statistical activation within a pre-specified region of interest.
Disability Rating Scale (DRS) total score	6 months post injury	The Disability Rating Scale (DRS) provides quantitative information regarding functional disability in patients recovering from severe brain injury. The total score on the DRS ranges from 0 to 29 with higher scores indicating a greater degree of disability. DRS subscale scores include eye opening \[score range 0-3\], communication \[score range 0-4\], motor response \[score range 0-5\], cognitive ability for feeding \[score range 0-3\], cognitive ability for toileting \[score range 0-3\], cognitive ability for grooming \[score range 0-3\], level of function \[score range 0-5\], and employability \[score range 0-3\]. Subscale scores are summed to produce the total score.

Trial Locations

Locations (2)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

UW Health University Hospital; 🇺🇸 Madison, Wisconsin, United States