UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study

NCT03284307 | Completed Phase 4 Results DMC FDA Drug

• 4 other identifiers: 2015-1399A530900SMPH\ANESTHESIOLOGY\ANESTHESIOProtocol Version 10/18/2019
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Unconsciousness; Consciousness

Keywords

Sedation; Propofol; Dexmedetomidine; Ketamine; Sevoflurane; Electroencephalogram

Outcome Measures

Primary Outcomes (1)

• Occipital Delta Power Spectral Density by Conscious State and Study Group.

  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.

  Intraoperative (During sedation-- up to 8 hours)

Secondary Outcomes (4)

• Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).

  Intraoperative (During sedation-- up to 8 hours)

• Effect of Study Drug on Ability to Correctly Identify Shapes/Images

  Intraoperative (During sedation-- up to 8 hours)

• Effect of Study Drug on Ability to Correctly Identify Images

  Intraoperative (During sedation-- up to 8 hours)

• Effect of Study Drug on Ability to Form Implicit Memory

  Intraoperative (During sedation-- up to 8 hours)

Study Arms (1)

Drug Administrated

EXPERIMENTAL

Sedatives will be administered to participants while their brain activity is measured.

Drug: Dexmedetomidine; Drug: Ketamine; Drug: Propofol; Drug: Midazolam

Interventions

Dexmedetomidine DRUG

20 participants will be administered Dexmedetomidine.

Drug Administrated

Ketamine DRUG

20 participants will be administered Ketamine.

Drug Administrated

Propofol DRUG

20 participants will be administered Propofol.

Drug Administrated

Midazolam DRUG

20 participants will be administered Midazolam.

Drug Administrated

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

UW Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (4)

• Wehrman JJ, Casey C, Redinbaugh MJ, Muller E, Munn B, Payne T, Tanabe S, Mohanta S, Filbey W, Raz A, Banks MI, Pearce RA, Shine JM, Saalmann YB, Sanders RD. Thalamic contributions to predictive coding and disconnected consciousness in human volunteers. Br J Anaesth. 2025 Nov 27:S0007-0912(25)00776-7. doi: 10.1016/j.bja.2025.10.038. Online ahead of print.

  PMID: 41314941 DERIVED

• Casey CP, Tanabe S, Farahbakhsh ZZ, Parker M, Bo A, White M, Ballweg T, Mcintosh A, Filbey W, Banks MI, Saalmann YB, Pearce RA, Sanders RD. Evaluation of putative signatures of consciousness using specific definitions of responsiveness, connectedness, and consciousness. Br J Anaesth. 2024 Feb;132(2):300-311. doi: 10.1016/j.bja.2023.09.031. Epub 2023 Oct 31.

  PMID: 37914581 DERIVED

• Wehrman JJ, Casey C, Tanabe S, Mohanta S, Filbey W, Weber L, Banks MI, Pearce RA, Saalmann Y, Sanders RD. Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection. Br J Anaesth. 2023 Oct;131(4):705-714. doi: 10.1016/j.bja.2023.06.044. Epub 2023 Aug 3.

  PMID: 37541951 DERIVED

• 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.

  PMID: 35148892 DERIVED

MeSH Terms

Conditions

Unconsciousness

Interventions

Dexmedetomidine; Ketamine; Propofol; Midazolam

Condition Hierarchy (Ancestors)

Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The fourth study drug was changed from sevoflurane to midazolam in November of 2019 due to concerns about conducting experiments in patients inhaling a volatile anesthetic through a face mask and the difficulty we would have with communicating with patients. The cessation of human subjects research due to the COVID-19 pandemic and amended institutional guidelines for conducting in-person research caused far fewer participants to be recruited than was planned.

Results Point of Contact

• Title: Robert Sanders, MBBS, PhD, FRCA
• Organization: University of Sydney

robert.sanders@sydney.edu.au

02 9036 3136

Study Officials

• Robert A Pearce, MD, PhD

  Professor and chair of Anesthesiology at UW- Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: September 15, 2017
• Study Start: August 10, 2017
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: April 13, 2023
• Results First Posted: April 10, 2023

Record last verified: 2023-04

Locations

US (1)