UnconsciousnessPhase 4UN-CONSCIOUSNCT03284307

UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study

A Phase 4 study testing Dexmedetomidine, Ketamine and Propofol in people with Unconsciousness and Consciousness, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Unconsciousness, Consciousness
What is being tested?: Dexmedetomidine, Ketamine and Propofol
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 1 siteUnited States
Study dates: 10 Aug 2017to 12 Mar 2020
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 27Show fewer

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.
o Resting heart Rate<60 bpm
o Reported egg allergy
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

Trial locations and contacts

1 site in 1 country.

United States1 site

UW Hospital and Clinics
Madison, Wisconsin, 53792

Other trials in United States

About this study

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.

Read the 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.

Conditions: Unconsciousness, Consciousness
Being tested: Dexmedetomidine, Ketamine, Propofol, Midazolam
Keywords: Sedation, Propofol, Dexmedetomidine, Ketamine, Sevoflurane, Electroencephalogram
Medical subject headings: Unconsciousness

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DexmedetomidineDrug
20 participants will be administered Dexmedetomidine.
KetamineDrug
20 participants will be administered Ketamine.
PropofolDrug
20 participants will be administered Propofol.
MidazolamDrug
20 participants will be administered Midazolam.

Study groups in NCT03284307
Study group	Role	What they receive
Drug Administrated	Experimental	Sedatives will be administered to participants while their brain activity is measured. Receives: Drug: Dexmedetomidine; Drug: Ketamine; Drug: Propofol; Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
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.
Measured: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Correctly Identify Shapes/Images
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.
Measured: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Correctly Identify Images
The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.
Measured: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Form Implicit Memory
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.
Measured: Intraoperative (During sedation-- up to 8 hours)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Aug 201712 Mar 2020

First posted15 Sep 2017
Study start10 Aug 2017
Primary completion12 Mar 2020
Study completion12 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for UnconsciousnessStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03284307
Sponsor's protocol ID: 2015-1399
Other IDs: A530900, SMPH\ANESTHESIOLOGY\ANESTHESIO, Protocol Version 10/18/2019
Acronym: UN-CONSCIOUS
Status last verified: Apr 2023
First submitted: 22 Aug 2017
Last updated: 13 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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. 2026 Feb;136(2):573-583. doi: 10.1016/j.bja.2025.10.038. Epub 2025 Nov 27.
PubMed 41314941
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.
PubMed 37914581
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.
PubMed 37541951
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.
PubMed 35148892

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Unconsciousness trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study
ClinicalTrials.gov ID: NCT03284307
Acronym / sponsor ID: UN-CONSCIOUS / 2015-1399
Conditions: Unconsciousness, Consciousness
Keywords: Sedation, Propofol, Dexmedetomidine, Ketamine, Sevoflurane, Electroencephalogram
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: University of Wisconsin, MadisonUniversity, hospital or other
Study start: 10 Aug 2017 (actual)
Primary completion: 12 Mar 2020 (actual)
Study completion: 12 Mar 2020 (actual)
First posted: 15 Sep 2017 (actual)
Results: Posted 10 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Drug Administrated	Experimental	Drug: Dexmedetomidine, Drug: Ketamine, Drug: Propofol, Drug: MidazolamSedatives will be administered to participants while their brain activity is measured.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (27 listed)

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:
BMI > 35

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dexmedetomidine20 participants will be administered Dexmedetomidine.	Drug	Drug Administrated
Ketamine20 participants will be administered Ketamine.	Drug	Drug Administrated
Propofol20 participants will be administered Propofol.	Drug	Drug Administrated
Midazolam20 participants will be administered Midazolam.	Drug	Drug Administrated

Primary outcome

Occipital Delta Power Spectral Density by Conscious State and Study Group.
Time frame: 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.

4 secondary outcomes

Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).
Time frame: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Correctly Identify Shapes/Images
Time frame: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Correctly Identify Images
Time frame: Intraoperative (During sedation-- up to 8 hours)
Effect of Study Drug on Ability to Form Implicit Memory
Time frame: Intraoperative (During sedation-- up to 8 hours)

Results and safety

Results posted to the registry on 10 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Study Participants	35	27

Primary outcome: Occipital Delta Power Spectral Density by Conscious State and Study Group.

Time frame: Intraoperative (During sedation-- up to 8 hours). Least squares mean (95% Confidence Interval). Unit: log10(μV^2)

Measure	Dexmedetomidine n = 20	Ketamine n = 15	Propofol n = 6	Midazolam n = 0	Sleep n = 15
Connected Consciousness	2.37 (2.31 to 2.46)	1.62 (1.57 to 1.68)	2.05 (1.94 to 2.15)	–	2.1 (2.03 to 2.18)
Disconnected Consciousness	2.57 (2.53 to 2.61)	1.7 (1.57 to 1.84)	2.34 (2.22 to 2.5)	–	2.58 (2.52 to 2.65)
Unconsciousness	2.68 (2.61 to 2.75)	1.46 (1.16 to 1.83)	2.51 (2.31 to 2.68)	–	2.63 (2.47 to 2.83)

Dexmedetomidine: Slope: 0.110, p = 0.012, Mixed Models Analysis
Ketamine: Slope: -0.238, p = 0.236, Mixed Models Analysis
Propofol: Slope: 0.166, p = 0.174, Mixed Models Analysis

Population analysed: No midazolam visit was ever conducted because no interested participants had reached that step of the drug sequence after it was added to the protocol in November of 2019.This was in large part due to the shutdown of in-person research activities in March of 2020 from the COVID-19 pandemic.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 hours after drug or sleep visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dexmedetomidine	0 of 20 (0%)	5 of 20 (25%)	0 of 20
Ketamine	0 of 15 (0%)	6 of 15 (40%)	0 of 15
Propofol	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Midazolam	0 of 0	0 of 0	0
Sleep	0 of 15 (0%)	0 of 15 (0%)	0 of 15

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41314941Wehrman 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. 2026 Feb;136(2):573-583. doi: 10.1016/j.bja.2025.10.038. Epub 2025 Nov 27.
Derived from this study: PubMed 37914581Casey 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.
Derived from this study: PubMed 37541951Wehrman 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.
Derived from this study: PubMed 35148892Casey 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert A Pearce, MD, PhD principal investigator

Professor and chair of Anesthesiology at UW- Madison

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dexmedetomidine, Ketamine and Propofol in people with Unconsciousness and Consciousness, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occipital Delta Power Spectral Density by Conscious State and Study Group. (time frame: Intraoperative (During sedation-- up to 8 hours)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03284307, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2023.