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

NCT06568536 | Recruiting DMC

• 2 other identifiers: 2024P0018051R01NS138257-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

Consciousness Disorders

Keywords

unresponsive wakefulness syndrome; vegetative state; minimally conscious state; transcranial magnetic stimulation; electroencephalography; traumatic brain injury; coma recovery scale - revised; functional electroencephalogram; functional imaging

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Patients with acute disorders of consciousness receiving TMS-EEG

EXPERIMENTAL

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

Interventions

Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG OTHER

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

Patients with acute disorders of consciousness receiving TMS-EEG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18
• Functionally independent at baseline
• Acquired brain injury within the last 28 days
• 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
• Continuous intravenous sedation able to be discontinued for at least 10 minutes
• ICU clinicians approve safe placement of 64-electrode EEG cap on the scalp

You may not qualify if:

• Status epilepticus or uncontrolled seizure disorder
• 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)
• Medical instability, restlessness, or other factors identified by the PI that would either prevent safe participation or compromise data acquisition
• Hemicraniectomy
• If a subject meets a contraindication for MR imaging, the subject may participate in all other aspects of the study except MRI.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

UW Health University Hospital

Madison, Wisconsin, 53792, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Brian L. Edlow, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian L. Edlow, MD

CONTACT

617-724-6352; bedlow@mgh.harvard.edu

Melanie Boly, MD, PhD

CONTACT

boly@neurology.wisc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Of note, while this is not a "multi-arm" randomized controlled trial, the outcome assessor for the 6-month functional outcome will be blinded to the patient's level of consciousness that was assessed in the ICU.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC)

Model Details: 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

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 23, 2024
• Study Start: November 8, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

US (2)