Assessing Covert Consciousness in Unresponsive Patients

• ClinicalTrials.gov Identifier: NCT02659228
• Recruitment Status: Unknown
• First Posted: January 20, 2016
• Last Update Posted: October 27, 2016
• Sponsor: University of Michigan
• Collaborators: McGill University; McMaster University
• Information provided by (Responsible Party): George Mashour, University of Michigan

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.

Condition or disease	Intervention/treatment	Phase
Consciousness Disorders	Device: EEG recording; Drug: Anesthetics, Intravenous	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Assessing the Potential for 'Covert Consciousness' in Unresponsive Patients
• Study Start Date: December 2016
• Estimated Primary Completion Date: June 2017

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control 1 (negative control); Individuals with a diagnosis of UWS without neural markers of consciousness	Device: EEG recording; EEG recording with anesthetic (DIPRIVAN)
Active Comparator: Control 2 (positive control); Individuals with a diagnosis of MCS, who are behaviourally responsive and who present neural markers of consciousness	Device: EEG recording; EEG recording with anesthetic (DIPRIVAN)
Experimental: Target Population; Individuals with a clinical diagnosis of UWS, but who possess some neurophysiological signatures of conscious awareness	Device: EEG recording; EEG recording with anesthetic (DIPRIVAN); Drug: Anesthetics, Intravenous; The participant will receive an intravenous infusion of propofol (DIPRIVAN Injectable Emulsion USP 1%, AstraZeneca).

Outcome Measures

Primary Outcome Measures :

1. Asymmetry in feedback vs. feedforward network connectivity [ Time Frame: 3 hours ]
   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 :

1. Presence of P300 and N400 event-related potentials [ Time Frame: 3 hours ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: George Mashour, Bert N La De Professor of Anesthesiology Research, University of Michigan
• ClinicalTrials.gov Identifier: NCT02659228
• Other Study ID Numbers: 13-784
• First Posted: January 20, 2016
• Last Update Posted: October 27, 2016
• Last Verified: October 2016

Additional relevant MeSH terms:

Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Anesthetics; Anesthetics, Intravenous; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, General