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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Consciousness Disorders
• Intervention / Treatment: Other: Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG

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

Contacts and Locations

• Study Contact: Name: Brian L. Edlow, MD; Phone Number: 617-724-6352; Email: bedlow@mgh.harvard.edu
• Study Contact Backup: Name: Melanie Boly, MD, PhD; Email: boly@neurology.wisc.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Brian L Edlow, MD; Phone Number: 617-724-6352; Email: bedlow@mgh.harvard.edu
      • Principal Investigator: Brian L. Edlow, MD
      • Sub-Investigator: Matteo Fecchio, PhD
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Not yet recruiting
      • UW Health University Hospital
      • Principal Investigator: Melanie Boly, MD, PhD
      • Contact: Melanie Boly, MD, PhD

Participation Criteria

Eligibility Criteria

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

Study Population

Patients diagnosed with disorders of consciousness after acquired brain injury within the last 28 days and treated in the intensive care unit

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with acute disorders of consciousness receiving 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.

Other: Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG; The presence of consciousness will be classified considering the highest level of consciousness revealed by repeated behavioral examinations, functional electroencephalography (task-based EEG), and functional brain imagery (task-based fMRI). Based on the results of this composite standard reference, we will evaluate the diagnostic and prognostic accuracy of TMS-EEG measurements of brain complexity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of consciousness as defined by a composite reference standard for consciousness that combines behavior, task-based EEG, and task-based fMRI	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.	48 hours after the end of the TMS-EEG assessment
Disability Rating Scale (DRS) total score	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.	6 months post injury

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Brian L. Edlow, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: traumatic brain injury; functional imaging; minimally conscious state; transcranial magnetic stimulation; electroencephalography; vegetative state; unresponsive wakefulness syndrome; coma recovery scale - revised; functional electroencephalogram
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders
• Other Study ID Numbers: 2024P001805; 1R01NS138257-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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