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UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study (UN-CONSCIOUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03284307
Recruitment Status : Active, not recruiting
First Posted : September 15, 2017
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE August 22, 2017
First Posted Date  ICMJE September 15, 2017
Last Update Posted Date October 8, 2021
Actual Study Start Date  ICMJE August 10, 2017
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
Spontaneous EEG slow wave activity [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
The difference in spontaneous EEG slow wave activity over posterior cortex between consciousness and unconsciousness is measured with high-density EEG equipment and reported in spectral power in the delta band at electrode Oz.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2017)
Spontaneous EEG slow wave activity [ Time Frame: Intraoperative (During sedation) ]
Investigate the difference in spontaneous EEG slow wave activity over posterior cortex between consciousness and unconsciousness.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • Incidence of disconnected conscious experience (dreaming) vs connected conscious experience (awareness of external world). [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    The incidence of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry.
  • Difference in high-density EEG responses assessed by calculation of the phase locking factor following auditory stimulation [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    Difference in high-density EEG responses assessed by calculation of the phase locking factor following auditory stimulation between conscious experience under sedation and lack of conscious experience. Phase locking factor is calculated by taking the Hilbert transform of the evoked response and quantifying the alignment of phases based on the imaginary component of the signal. Phase locking factor is quantified on a scale of 0 to 1, with 0 being no phase locking and 1 being maximal phase locking.
  • Effect of study drug on percent difference in duration of phase locking factor [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    Phase locking factor will be calculated (as described previously) and compared between data collected at baseline and data collected after varying doses of drug have been administered. Effect size will be reported as a percentage of the reference group.
  • Effect of consciousness on phase locking factor after auditory stimulation [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    Phase locking factor will be calculated (as described previously) and compared between data collected during different states of consciousness (as assessed by subject report). Effect size will be reported as a percentage of the reference group.
  • Effect of study drug on ability to correctly identify shapes/images [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    The ability to identify shapes/images in visual illusions measured by the NIH Toolbox and match sounds and images measured by the predictive coding task. Will be reported by a percent correct from the predictive coding task and total score from NIH Toolbox.
  • Effect of study drug on ability to form implicit memory [ Time Frame: Intraoperative (During sedation-- up to 8 hours) ]
    Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the number correct responses out of sixteen.
  • Incidence of EEG wave patterns during sedation vs natural sleep [ Time Frame: Intraoperative (During sedation and sleep visit-- up to 18 hours cumulative) ]
    Low frequency (<4 Hz) spectral power will be measured using high-density EEG acquired during natural sleep as well as during sedation. The magnitude of this spectral power will be compared across conditions and reported as a percentage relative to natural sleep.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study
Official Title  ICMJE UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study
Brief Summary This study will be a single-site, controlled, unblinded study at the University of Wisconsin to examine changes in the electroencephalogram during anesthesia and waking.
Detailed Description

* 20 subjects will be recruited per drug, and subjects can be recruited to undergo multiple sedation protocols.

Screening:

Subjects will respond to the volunteer posts for the study by calling into a study specific phone number. They will complete a phone screening to determine basic eligibility for the study. At the beginning of the sedation session, participants will affirm that in the interval since their baseline visit, they have not acquired any of the cited exclusion criteria that would preclude participation. A review of these exclusion criteria will be completed by the Anesthesiologist. A standard pre-anesthetic assessment will be performed, including confirmation of NPO status, and documented using the standard Department of Anesthesiology pre-operative evaluation form.

The first sedative will be dexmedetomidine followed by ketamine, propofol and then midazolam (dependent on the availability of the drugs). Total enrollment in the study will be up to 80 subjects. Each sedation experiment will occur on separate days at least 28 days apart, if the subject chooses to participate in more than one session.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Unconsciousness
  • Consciousness
Intervention  ICMJE
  • Drug: Dexmedetomidine
    20 participants will be administered Dexmedetomidine.
  • Drug: Ketamine
    20 participants will be administered Ketamine.
  • Drug: Propofol
    20 participants will be administered Propofol.
  • Drug: Midazolam
    20 participants will be administered Midazolam.
Study Arms  ICMJE Experimental: Drug Administrated
Sedatives will be administered to participants while their brain activity is measured.
Interventions:
  • Drug: Dexmedetomidine
  • Drug: Ketamine
  • Drug: Propofol
  • Drug: Midazolam
Publications * Casey CP, Tanabe S, Farahbakhsh Z, Parker M, Bo A, White M, Ballweg T, Mcintosh A, Filbey W, Saalmann Y, Pearce RA, Sanders RD. Distinct EEG signatures differentiate unconsciousness and disconnection during anaesthesia and sleep. Br J Anaesth. 2022 Jun;128(6):1006-1018. doi: 10.1016/j.bja.2022.01.010. Epub 2022 Feb 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 2, 2021)
30
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2017)
80
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18-40
  • In good health, determined by the PI on the basis of medical history and a standard assessment for anesthesia to be documented as part of the study record
  • Right handed, to standardize for asymmetry in brain functions

Exclusion Criteria:

  • Adults <18 years old or >40 years old
  • Pregnancy confirmed on pregnancy test on day of sedation
  • Contraindication to anesthesia or allergy to study drug
  • Difficult anesthesia: American Society of Anesthesiologists Physical Status greater than 1, per the discretion of the PI. Examples of ASA status include, but are not limited to:

    • Any systemic disease present, such as diabetes, cardiac, pulmonary, or other acute or chronic disorder, or history of smoking
    • Narrow angle glaucoma
    • Abnormal airway examination
    • Any abnormality on medical history and physical examination
    • Snoring or sleep disorders including apnea
    • Antecedent pulmonary aspiration risk (e.g., history GI reflux, heartburn, hiatal hernia)
    • Adverse reaction or allergy with anesthesia or other sedatives
    • Chronic medication use
    • History of difficult anesthesia, laryngoscopy or intubation
    • Family history of difficulty with anesthesia or sedation
    • History of vertigo, nausea or vomiting after anesthesia
  • BMI > 35
  • Contraindication to HD-EEG, TMS or MRI for relative parts of the procedures. MRI exclusion criteria: presence of metallic or electronic implants; history of claustrophobia. TMS exclusion criteria: Presence or history of medical conditions that could increase the chance of seizures (e.g. - stroke, aneurysm, brain surgery, structural brain lesion) cranial metal implants; structural brain lesion; devices that may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain stimulator); history of head trauma with loss of consciousness for greater than 5 minutes; family history of seizures; history of antecedent mood disorder.
  • Exclusion from Dexmedetomidine:

    o Resting heart Rate<60 bpm

  • Exclusion from Propofol:

    o Reported egg allergy

  • Exclusion from Ketamine:

    • History of post-operative nausea and vomiting
    • History of motion sickness

Additional exclusion criteria on the day of sedation:

  • Anything to eat or drink for the preceding 8 hours
  • Any use of over-the-counter or recreational drugs (including alcohol or tobacco) within the preceding 24 hours
  • Any use of sedative or sleep agents within the preceding 24 hours
  • Recent change in health, including cough, cold, or fever
  • Exposure to anesthesia or sedation in the last 6 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03284307
Other Study ID Numbers  ICMJE 2015-1399
A530900 ( Other Identifier: UW Madison )
SMPH\ANESTHESIOLOGY\ANESTHESIO ( Other Identifier: UW Madison )
Protocol Version 10/18/2019 ( Other Identifier: UW Madison )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of Wisconsin, Madison
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Wisconsin, Madison
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert A Pearce, MD, PhD Professor and chair of Anesthesiology at UW- Madison
PRS Account University of Wisconsin, Madison
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP