Assessing Covert Consciousness in Unresponsive Patients
Primary Purpose
Consciousness Disorders
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
EEG recording
Anesthetics, Intravenous
Sponsored by
About this trial
This is an interventional basic science trial for Consciousness Disorders
Eligibility Criteria
Inclusion Criteria:
Patients admitted to the intensive care unit at Hamilton General Hospital who:
- Clinical status consistent with UWS (no responsiveness to commands)
- Clinical status consistent with MCS (minimal response to at least one command)
- Presence of an endotracheal tube (ETT) or a tracheostomy tube
- Between 18 and 50 years of age
Exclusion Criteria:
• Elevated intracranial pressure (ICP)
- Hepatic or renal failure
- Hemodynamic instability
- Active vasopressor therapy
- Previous open-head injury
- Previous intracranial pathology requiring neurosurgical interventions in the past 72 hours
- Anticipated ICU stay < 24 hours
- Documented allergy to propofol
- Pregnancy
- BMI > 35 kg/m2
- Anyone who is deemed medically unsuitable for this study by the attending intensivist
- Patients who are already in a medically-induced coma for intracranial hypertension or status epilepticus
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Active Comparator
Experimental
Arm Label
Control 1 (negative control)
Control 2 (positive control)
Target Population
Arm Description
Individuals with a diagnosis of UWS without neural markers of consciousness
Individuals with a diagnosis of MCS, who are behaviourally responsive and who present neural markers of consciousness
Individuals with a clinical diagnosis of UWS, but who possess some neurophysiological signatures of conscious awareness
Outcomes
Primary Outcome Measures
Asymmetry in feedback vs. feedforward network connectivity
EEG networks will be monitored pre, during and post anesthesia. Directed connectivity will be calculated using phase lag index (PLI) and symbolic transfer entropy (STE) between all combinations of EEG sensors. Average values of feedback connectivity (e.g. from the frontal regions to parietal and occipital regions) will be compared to average values of feedforward connectivity (e.g. from parietal and occipital regions to frontal regions). Positive asymmetry will be correlated to the presence of conscious awareness and negative asymmetry will be correlated to the absence of conscious awareness.
Secondary Outcome Measures
Presence of P300 and N400 event-related potentials
EEG signals will be processed to extract the event-related EEG reactions to the auditory stimulation paradigm. Signals will be average 300 ms post-stimuli and 400 ms post-stimuli to assess the presence of the P300 and N400 event-related potentials. Presence of these event-related potentials will be correlated to the presence of conscious awareness and absence of these event-related potentials will be correlated to the absence of conscious awareness.
Full Information
NCT ID
NCT02659228
First Posted
January 8, 2016
Last Updated
October 25, 2016
Sponsor
University of Michigan
Collaborators
McGill University, McMaster University
1. Study Identification
Unique Protocol Identification Number
NCT02659228
Brief Title
Assessing Covert Consciousness in Unresponsive Patients
Official Title
Assessing the Potential for 'Covert Consciousness' in Unresponsive Patients
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
December 2016 (undefined)
Primary Completion Date
June 2017 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
McGill University, McMaster University
4. Oversight
5. Study Description
Brief Summary
In this study, the investigators explore anesthesia as a tool for providing further insight into the level of consciousness of individuals with a clinical diagnosis of unresponsive wakefulness syndrome (UWS), but who possess some neurophysiological signatures of conscious awareness. This group, who could potentially be conscious, will herein be referred to as the target population. Our goal is to assess whether or not neurological patterns of consciousness in the target population respond to anesthesia in a similar manner to neurologically compromised individuals with known consciousness (e.g. those in minimally conscious state (MCS). In healthy controls, propofol-induced unconsciousness results in an elimination of the mismatch negativity event-related brain potential (ERP) and a diminished directed connectivity. The investigators hypothesize that at doses well below those required for surgery, anesthesia will have similar effects on these neural patterns in neurologically compromised patients with the potential for conscious awareness, but will not affect these patterns in those who lack consciousness.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Consciousness Disorders
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control 1 (negative control)
Arm Type
Placebo Comparator
Arm Description
Individuals with a diagnosis of UWS without neural markers of consciousness
Arm Title
Control 2 (positive control)
Arm Type
Active Comparator
Arm Description
Individuals with a diagnosis of MCS, who are behaviourally responsive and who present neural markers of consciousness
Arm Title
Target Population
Arm Type
Experimental
Arm Description
Individuals with a clinical diagnosis of UWS, but who possess some neurophysiological signatures of conscious awareness
Intervention Type
Device
Intervention Name(s)
EEG recording
Intervention Description
EEG recording with anesthetic (DIPRIVAN)
Intervention Type
Drug
Intervention Name(s)
Anesthetics, Intravenous
Intervention Description
The participant will receive an intravenous infusion of propofol (DIPRIVAN Injectable Emulsion USP 1%, AstraZeneca).
Primary Outcome Measure Information:
Title
Asymmetry in feedback vs. feedforward network connectivity
Description
EEG networks will be monitored pre, during and post anesthesia. Directed connectivity will be calculated using phase lag index (PLI) and symbolic transfer entropy (STE) between all combinations of EEG sensors. Average values of feedback connectivity (e.g. from the frontal regions to parietal and occipital regions) will be compared to average values of feedforward connectivity (e.g. from parietal and occipital regions to frontal regions). Positive asymmetry will be correlated to the presence of conscious awareness and negative asymmetry will be correlated to the absence of conscious awareness.
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
Presence of P300 and N400 event-related potentials
Description
EEG signals will be processed to extract the event-related EEG reactions to the auditory stimulation paradigm. Signals will be average 300 ms post-stimuli and 400 ms post-stimuli to assess the presence of the P300 and N400 event-related potentials. Presence of these event-related potentials will be correlated to the presence of conscious awareness and absence of these event-related potentials will be correlated to the absence of conscious awareness.
Time Frame
3 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients admitted to the intensive care unit at Hamilton General Hospital who:
Clinical status consistent with UWS (no responsiveness to commands)
Clinical status consistent with MCS (minimal response to at least one command)
Presence of an endotracheal tube (ETT) or a tracheostomy tube
Between 18 and 50 years of age
Exclusion Criteria:
• Elevated intracranial pressure (ICP)
Hepatic or renal failure
Hemodynamic instability
Active vasopressor therapy
Previous open-head injury
Previous intracranial pathology requiring neurosurgical interventions in the past 72 hours
Anticipated ICU stay < 24 hours
Documented allergy to propofol
Pregnancy
BMI > 35 kg/m2
Anyone who is deemed medically unsuitable for this study by the attending intensivist
Patients who are already in a medically-induced coma for intracranial hypertension or status epilepticus
12. IPD Sharing Statement
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Assessing Covert Consciousness in Unresponsive Patients
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