Development of a Point of Care System for Automated Coma Prognosis

NCT03826407 | Unknown DMC

• 3 other identifiers: ComaML2018CPG158287CHRP 523461-18
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Coma; Disorder of Consciousness; Minimally Conscious State; Vegetative State; Neuropathology

Keywords

Coma; Machine Learning; Prognosis; Electrophysiology; Event-related potentials; Electroencephalography; Mismatch Negativity; Auditory Brainstem Response; Disorders of Consciousness; EEG; ERP

Outcome Measures

Primary Outcomes (5)

• Change in multiple electrophysiological measures across specified time points during coma

  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.

  up to 30 days from date of recruitment

• Change in multiple electrophysiological measures across specified time points during MCS or UWS

  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.

  up to 6 months from date of recruitment

• Correlation between behavioral and electrophysiological measures after coma/DOC emergence

  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.

  Within a 30-day time period post recruitment

• Sensitivity and specificity of prognostic capabilities of electrophysiological measures

  Analyses will compare the electrophysiological measures as outcome predictors to traditional behaviorally-based tools.

  Within a 30-day time period post recruitment

• Feasibility of procedure

  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.

  up to 6 months from date of recruitment

Secondary Outcomes (2)

• Correlation between individual patient factors, EEG results, and outcome for coma

  up to 30 days from date of recruitment

• Correlations between individual patient factors, EEG results, and outcome for DOC

  up to 6 months from date of recruitment

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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).

You may not qualify if:

• 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:
• ≥ 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
• (During the COVID-19 pandemic only)
• ≥ 60 years of age
• have a weakened immune system

Sponsors & Collaborators

• McMaster University: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Natural Sciences and Engineering Research Council, Canada: collaborator
• Hamilton Health Sciences Corporation: collaborator
• Brain Vision Solutions Inc.: collaborator
• McGill University: collaborator

Study Sites (1)

McMaster University Hamilton Health Sciences / Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (27)

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MeSH Terms

Conditions

Coma; Consciousness Disorders; Persistent Vegetative State

Condition Hierarchy (Ancestors)

Unconsciousness; 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

Study Officials

• John F Connolly, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Alison Fox-Robichaud, MD

  Hamilton Health Sciences - Hamilton General site

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: February 1, 2019
• Study Start: October 1, 2019
• Primary Completion: August 12, 2022
• Study Completion: December 1, 2023
• Last Updated: February 6, 2023

Record last verified: 2023-02

Locations

CA (1)