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NCT03284307: UN-CONSCIOUS

UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study

Completed Phase 4 Results posted Last updated 13 April 2023
What this trial tests

Phase 4 trial testing Dexmedetomidine in Unconsciousness in 35 participants. Completed in 12 March 2020.

Timeline
10 August 2017
Primary endpoint
12 March 2020
12 March 2020

Quick facts

Lead sponsorUniversity of Wisconsin, Madison
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposebasic science
Enrollment35
Start date10 August 2017
Primary completion12 March 2020
Estimated completion12 March 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Wisconsin, Madison

Who can join

Adults 18 to 40, any sex, with Unconsciousness or Consciousness. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Occipital Delta Power Spectral Density by Conscious State and Study Group. Primary · Intraoperative (During sedation-- up to 8 hours)

The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep.

Connected Consciousness
GroupValue95% CI
Dexmedetomidine2.372.31 – 2.46
Ketamine1.621.57 – 1.68
Propofol2.051.94 – 2.15
Sleep2.12.03 – 2.18
Disconnected Consciousness
GroupValue95% CI
Dexmedetomidine2.572.53 – 2.61
Ketamine1.71.57 – 1.84
Propofol2.342.22 – 2.5
Sleep2.582.52 – 2.65
Unconsciousness
GroupValue95% CI
Dexmedetomidine2.682.61 – 2.75
Ketamine1.461.16 – 1.83
Propofol2.512.31 – 2.68
Sleep2.632.47 – 2.83
Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World). Secondary · Intraoperative (During sedation-- up to 8 hours)

The number of instances 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.

Instances of Connected Consciousness
GroupValue95% CI
Dexmedetomidine70
Ketamine180
Propofol56
Instances of Disconnected Consciousness
GroupValue95% CI
Dexmedetomidine226
Ketamine30
Propofol22
Effect of Study Drug on Ability to Correctly Identify Shapes/Images Secondary · Intraoperative (During sedation-- up to 8 hours)

The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control \& Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy \>=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test.

Baseline NIH Toolbox Card Sorting Score
GroupValue95% CI
Dexmedetomidine8.83± 1.21
Ketamine9.29± 0.59
Propofol9.45± 0.95
Sedation NIH Toolbox Card Sorting Score
GroupValue95% CI
Dexmedetomidine7.85± 1.49
Ketamine8.2± 0.99
Propofol6.94± 4.16
Baseline NIH Toolbox Flanker Score
GroupValue95% CI
Dexmedetomidine9.14± 0.67
Ketamine8.99± 0.83
Propofol9.48± 0.12
Sedation NIH Toolbox Flanker Score
GroupValue95% CI
Dexmedetomidine6.62± 0.88
Ketamine8.47± 0.93
Propofol8.36± 0.96
Effect of Study Drug on Ability to Correctly Identify Images Secondary · Intraoperative (During sedation-- up to 8 hours)

The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.

Baseline Predictive Coding Task Accuracy
GroupValue95% CI
Dexmedetomidine0.916± 0.07
Ketamine0.899± 0.07
Propofol0.91± 0.09
Sedation Predictive Coding Task Accuracy
GroupValue95% CI
Dexmedetomidine0.793± 0.09
Ketamine0.763± 0.1
Propofol0.734± 0.15
Effect of Study Drug on Ability to Form Implicit Memory Secondary · 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 average number of correct responses out of sixteen.

GroupValue95% CI
Dexmedetomidine8± 2.47
Ketamine8.17± 1.70
Propofol9± 1.58

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 hours after drug or sleep visit.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dexmedetomidine
Serious: 0/20 (0%)
Deaths: 0/20
Ketamine
Serious: 0/15 (0%)
Deaths: 0/15
Propofol
Serious: 0/6 (0%)
Deaths: 0/6
Midazolam
Serious: 0
Deaths: 0
Sleep
Serious: 0/15 (0%)
Deaths: 0/15
Other adverse events (8 terms — click to expand)

ReactionSystemDexmedetomidineKetaminePropofolMidazolamSleep
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
HypotensionCardiac disorders
BradycardiaCardiac disorders
Mild Chest PainCardiac disorders
Pain at injection siteInjury, poisoning and procedural complications
HeadacheNervous system disorders
BruisingInjury, poisoning and procedural complications

Data from ClinicalTrials.gov NCT03284307 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Distinct EEG signatures differentiate unconsciousness and disconnection during anaesthesia and sleep.
    Casey CP, Tanabe S, Farahbakhsh Z, Parker M, et al · · 2022 · cited 51× · PMID 35148892 · DOI 10.1016/j.bja.2022.01.010
  2. Evaluation of putative signatures of consciousness using specific definitions of responsiveness, connectedness, and consciousness.
    Casey CP, Tanabe S, Farahbakhsh ZZ, Parker M, et al · · 2024 · cited 17× · PMID 37914581 · DOI 10.1016/j.bja.2023.09.031
  3. Neuronal connected burst cascades bridge macroscale adaptive signatures across arousal states.
    Munn BR, Müller EJ, Medel V, Naismith SL, et al · · 2023 · cited 16× · PMID 37891167 · DOI 10.1038/s41467-023-42465-2
  4. Predictive Feedback, Early Sensory Representations, and Fast Responses to Predicted Stimuli Depend on NMDA Receptors.
    Mohanta S, Afrasiabi M, Casey CP, Tanabe S, et al · · 2021 · cited 14× · PMID 34732525 · DOI 10.1523/jneurosci.1311-21.2021
  5. Dynamic causal modelling of auditory surprise during disconnected consciousness: The role of feedback connectivity.
    Casey CP, Tanabe S, Farahbakhsh Z, Parker M, et al · · 2022 · cited 13× · PMID 36209793 · DOI 10.1016/j.neuroimage.2022.119657
  6. Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.
    Wehrman JJ, Casey C, Tanabe S, Mohanta S, et al · · 2023 · cited 3× · PMID 37541951 · DOI 10.1016/j.bja.2023.06.044
  7. The relationship of bispectral index values to conscious state: an analysis of two volunteer cohort studies.
    Wehrman JJ, Schuller PJ, Casey CP, Scheinin A, et al · · 2025 · cited 1× · PMID 39665912 · DOI 10.1016/j.bja.2024.09.032
  8. Thalamic contributions to predictive coding and disconnected consciousness in human volunteers.
    Wehrman JJ, Casey C, Redinbaugh MJ, Muller E, et al · · 2026 · PMID 41314941 · DOI 10.1016/j.bja.2025.10.038

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Other trials of Dexmedetomidine

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