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Development of a Point of Care System for Automated Coma Prognosis

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ClinicalTrials.gov Identifier: NCT03826407
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : January 29, 2021
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Natural Sciences and Engineering Research Council, Canada
Hamilton Health Sciences Corporation
Brain Vision Solutions Inc.
McGill University
Information provided by (Responsible Party):
McMaster University

Brief Summary:
Electroencephalogram/event-related potentials (EEG/ERP) data will be collected from 50 participants in coma or other disorder of consciousness (DOC; i.e., Unresponsive Wakefulness Syndrome [UWS] or Minimally Conscious State [MCS]), clinically diagnosed using the Glasgow Coma Scale (GCS). For coma patients, EEG recordings will be conducted for up to 24 consecutive hours at a maximum of 5 timepoints, spanning 30 days from the date of recruitment, to track participants' clinical state. For DOC patients, there will be an initial EEG recording up to 24 hours, with possible subsequent weekly recordings up to 2 hours. An additional dataset from 40 healthy controls will be collected, each spanning up to a 12-hour recording period in order to formulate a baseline. Collected data are to form the basis for automatic analysis and detection of ERP components in DOC, using a machine learning paradigm. Salient features (i.e., biomarkers) extracted from the ERPs and resting-state EEG will be identified and combined in an optimal fashion to give an accurate indicator of prognosis.

Condition or disease
Coma Disorder of Consciousness Minimally Conscious State Vegetative State Neuropathology

Detailed Description:

The Problem: Coma is a state of unconsciousness with a variety of causes. Traditional tests for coma outcome prediction are mainly based on a set of clinical observations (e.g., pupillary constriction). Recently however, event-related potentials (ERPs; which are transient electroencephalogram [EEG] responses to auditory, visual, or tactile stimuli) have been introduced as useful predictors of a positive coma outcome (i.e., emergence). However, such tests require a skilled neurophysiologist, and such people are in short supply. Also, none of the current approaches has sufficient positive and negative predictive accuracies to provide definitive prognoses in the clinical setting.

Objective: The investigators will apply innovative machine learning methods to analyze patient EEGs (50 patients and 40 healthy controls) to develop a simple, objective, replicable, and inexpensive point of care system which can significantly improve the accuracy of coma prognosis relative to current methods. The physical requirements of the proposed system consist only of an EEG system (inexpensive in terms of medical equipment) and a conventional laptop computer.

Methodology: The investigators intend to extend the team's newest algorithms and develop machine learning tools for automatic analysis and detection of ERP components. Preliminary results by the team in this respect have been very promising. The most salient features (i.e., biomarkers) extracted from the ERP will be identified and combined in an optimal fashion to give an accurate indicator of prognosis. Features will be extracted from resting state brain networks and from network trajectories associated with the processing of ERP signals.

Significance: The proposed work will enable critical care physicians to assess coma prognosis with speed and accuracy. Thus, families and their health care team will be provided the most accurate information possible to guide discussions of goals of care and life-sustaining therapies in the context of dealing with the consequences of devastating neurological injury.

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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Development of a Point of Care System for Automated Coma Prognosis - A Prospective Cohort Study
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Coma

Group/Cohort
DOC patients
Patients in coma (GCS score of 3-8) or with other disorder of consciousness, primarily Minimally Conscious State (MCS) or Unresponsive Wakefulness Syndrome (UWS; also known as vegetative state)
Healthy Control
Matched healthy controls without current neurological diagnoses



Primary Outcome Measures :
  1. Change in multiple electrophysiological measures across specified time points during coma [ Time Frame: up to 30 days from date of recruitment ]
    Event-related potentials (ERP) and resting state periods will be assessed at the specified intervals as a difference between successive timepoints. The ERP measures will include amplitude and latency values of N1, P2, MMN, P3a, P3b, and N400 to assess different levels of conscious processing and presence of signs of a conscious state predictive of subsequent emergence. Also, resting EEG measures will be obtained at regular intervals. EEG/ERP data will be recorded for up to 24 consecutive hours at a maximum of 5 timepoints spanning 30 days from the date of recruitment to track the participants' progression. The date of the initial assessment will be denoted as Day 0, and the subsequent assessments will take place ideally on Day 3, Day 10, Day 20 and Day 30, unless there is a ≥ 2 point of change in the patient's GCS score. Change in all specified measures will be assessed across the up to 24-hour recordings taken at 5 different timepoints.

  2. Change in multiple electrophysiological measures across specified time points during MCS or UWS [ Time Frame: up to 6 months from date of recruitment ]
    Event-related potentials (ERP) and resting state periods will be assessed at the specified intervals as a difference between successive timepoints. The ERP measures will include amplitude and latency values of N1, P2, MMN, P3a, P3b, and N400 to assess different levels of conscious processing and presence of signs of a conscious state predictive of subsequent emergence. Also, resting EEG measures will be obtained at regular intervals. EEG/ERP data will be recorded for an initial period of up to 24 consecutive hours, followed by up to 2-hour long recordings that may be conducted approximately once a week until the patient either regains full consciousness, is no longer within the Hamilton Health Sciences system, or until 6 months from the date of their enrollment into the study, whichever occurs first. Change in all specified measures will be assessed across the recordings taken at each timepoint.

  3. Correlation between behavioral and electrophysiological measures after coma/DOC emergence [ Time Frame: Within a 30-day time period post recruitment ]
    Patient emergence will be monitored using the Glasgow Outcome Scale (GOS). In the case of patient emergence, the full electrophysiological test procedures are recorded to correlate with traditional behavioral measures. The electrophysiological measures obtained at this timepoint (emergence) will be compared to the same measures obtained at the different time points during coma/DOC (Outcome 1/2) to detect both clinically relevant change and possible prognostic markers that may have been obtained at an earlier test point.

  4. Sensitivity and specificity of prognostic capabilities of electrophysiological measures [ Time Frame: Within a 30-day time period post recruitment ]
    Analyses will compare the electrophysiological measures as outcome predictors to traditional behaviorally-based tools.

  5. Feasibility of procedure [ Time Frame: up to 6 months from date of recruitment ]
    The team will also evaluate whether the repeated EEG sessions, lasting up to 24 hours, during the coma/DOC duration is a feasible approach to predict the emergence and outcome from coma.


Secondary Outcome Measures :
  1. Correlation between individual patient factors, EEG results, and outcome for coma [ Time Frame: up to 30 days from date of recruitment ]
    The study also collects demographic, medical history, injury information, and other physiological markers from the patient's health record and concurrent physiological assessment during the study period. Analyses will assess correlations between these factors and coma outcome and EEG findings.

  2. Correlations between individual patient factors, EEG results, and outcome for DOC [ Time Frame: up to 6 months from date of recruitment ]
    The study also collects demographic, medical history, injury information, and other physiological markers from the patient's health record and concurrent physiological assessment during the study period. Analyses will assess correlations between these factors and DOC outcome and EEG findings.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The Coma/DOC Group will include 50 patients from the Intensive Care Units, Neurological Step Down Unit, or Coronary Care Unit at Hamilton General Hospital (Ontario, Canada) who are in coma (GCS score =3-8), or who have other disorders of consciousness (MCS or UWS).

The Control Group of 40 matched healthy controls will be recruited primarily from the Hamilton community (Ontario, Canada).

Criteria

Inclusion Criteria:

  • Patients (≥ 18 years of age) primarily admitted to the Intensive Care Units, Neurological Step Down Unit, or Coronary Care Unit at Hamilton General Hospital who are in coma with Glasgow Coma Scale (GCS) score of 3-8, or;
  • Patients (≥ 18 years of age) who have other disorders of consciousness, primarily Minimally Conscious State (MCS) or Unresponsive Wakefulness Syndrome (UWS; also known as vegetative state).

Exclusion Criteria:

  • Severe liver failure (i.e., Child-Pugh Class C)
  • Severe renal failure (i.e., Urea ≥ 40)
  • Previous open-head injury
  • Known primary and secondary central nervous system malignancy
  • Known hearing impairment
  • Previous intracranial pathology requiring neurosurgical interventions in the past 72 hours
  • Anyone who is deemed medically unsuitable for this study by the attending intensivists

Healthy Controls:

Inclusion:

  • ≥ 18 years of age
  • no visual, language, learning, or hearing problems
  • no history of neurological or psychiatric disorder
  • not currently taking any medications that act on the central nervous system, such as antidepressants, anxiolytics, or anti-epileptics

Exclusion:

(During the COVID-19 pandemic only)

  • ≥ 60 years of age
  • have a weakened immune system
  • have one or more of the COVID-19 high risk medical conditions, according to the government of Canada website: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/people-high-risk-for-severe-illness-covid-19.html.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03826407


Contacts
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Contact: Hope Morrison 2893396348 lmb_coma@mcmaster.ca
Contact: John F Connolly, PhD 9055259140 ext 21106 jconnol@mcmaster.ca

Locations
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Canada, Ontario
McMaster University Hamilton Health Sciences / Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: John F Connolly, PhD    1-905-525-9140 ext 27095    jconnol@mcmaster.ca   
Contact: Alison Fox-Robichaud, MD    1-905-521-2100 ext 40742    afoxrob@mcmaster.ca   
Principal Investigator: John F Connolly, PhD         
Principal Investigator: James Reilly, PhD         
Principal Investigator: Alison Fox-Robichaud, MD         
Principal Investigator: Stefanie Blain-Moraes, PhD         
Principal Investigator: Ranil Sonnadara, PhD         
Sub-Investigator: Morgan Johnson, MSc         
Sub-Investigator: Cindy Hamielec, MD         
Sub-Investigator: Rober Boshra, MSc         
Sub-Investigator: Richard Kolesar, MD         
Principal Investigator: Paniz Tavakoli, PhD         
Sub-Investigator: Adianes Herrera-Díaz, MSc         
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Natural Sciences and Engineering Research Council, Canada
Hamilton Health Sciences Corporation
Brain Vision Solutions Inc.
McGill University
Investigators
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Principal Investigator: John F Connolly, PhD McMaster University
Study Chair: Alison Fox-Robichaud, MD Hamilton Health Sciences - Hamilton General site
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03826407    
Other Study ID Numbers: ComaML2018
CPG158287 ( Other Grant/Funding Number: Canadian Institutes of Health Research )
CHRP 523461-18 ( Other Grant/Funding Number: Natural Sciences and Engineering Research Council )
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: January 29, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: To be decided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by McMaster University:
Coma
Machine Learning
Prognosis
Electrophysiology
Event-related potentials
Electroencephalography
Mismatch Negativity
Auditory Brainstem Response
Disorders of Consciousness
EEG
ERP
Additional relevant MeSH terms:
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Coma
Consciousness Disorders
Persistent Vegetative State
Unconsciousness
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases