Consciousness DisordersCOMPASSNCT06568536
Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU
A study testing Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG in people with Consciousness Disorders, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Consciousness Disorders
- What is being tested?
- Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Nov 2024to 1 Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Additional inclusion criteria are present in the study protocol.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Melanie Boly, MD, PhD contact
United States2 sites, 2 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brian L Edlow, MD, 617-724-6352, bedlow@mgh.harvard.edu
Brian L. Edlow, MD
- Not yet recruiting
UW Health University Hospital
Madison, Wisconsin, 53792
Melanie Boly, MD, PhD
Melanie Boly, MD, PhD
About this study
Official title: 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.
Read the 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.
- Conditions
- Consciousness Disorders
- Being tested
- Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG
- Keywords
- unresponsive wakefulness syndrome, vegetative state, minimally conscious state, transcranial magnetic stimulation, electroencephalography, traumatic brain injury, coma recovery scale - revised, functional electroencephalogram, functional imaging
- Medical subject headings
- Consciousness Disorders, Persistent Vegetative State, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEGOther
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 6 months post injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2024
- Study start8 Nov 2024
- Primary completionAug 2029 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Consciousness DisordersStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian L. Edlow, M.D., Massachusetts General Hospital
- Investigators
- Brian L. Edlow, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06568536
- Sponsor's protocol ID
- 2024P001805
- Other IDs
- 1R01NS138257-01
- Acronym
- COMPASS
- Status last verified
- May 2025
- First submitted
- 21 Aug 2024
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU (COMPASS)
- ClinicalTrials.gov ID
- NCT06568536
- Acronym / sponsor ID
- COMPASS / 2024P001805
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 8 Nov 2024 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 23 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Patients with acute disorders of consciousness receiving TMS-EEG | Experimental | Other: Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEGAdults 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEGThe 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 | Other | Patients with acute disorders of consciousness receiving TMS-EEG |
Primary outcome
Presence of consciousness as defined by a composite reference standard for consciousness that combines behavior, task-based EEG, and task-based fMRI
Time frame: 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
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Melanie Boly, MD, PhD contact
Brian L. Edlow, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repeated behavioral assessments, functional electroencephalography and brain imagery, TMS-EEG in people with Consciousness Disorders, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brian L. Edlow, MD (617-724-6352, bedlow@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of consciousness as defined by a composite reference standard for consciousness that combines behavior, task-based EEG, and task-based fMRI (time frame: 48 hours after the end of the TMS-EEG assessment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.