Anesthesia AwarenessPhase 2MSINCT03498391
A Study of Human Multi-Sensory Integration
A Phase 2 study testing Propofol and Ketamine Injectable Product in people with Anesthesia Awareness, run by University of Pennsylvania at 1 site in United States.
Trial summary
The primary aim of this study is to determine whether spatiotemporal characteristics of multisensory evoked potentials can be used as a marker of consciousness (awareness) under anesthesia. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anesthesia Awareness
- What is being tested?
- Propofol and Ketamine Injectable Product
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2018to May 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers ages 18-65 years old
- American Society of Anesthesiologists (ASA) Physical Status I or II (i.e. healthy)
- Body Mass Index <30 kg/m2
- Easily visible uvula
Who cannot join
- Contraindications to administration of either propofol or ketamine
- Allergy to either one of the medications or preservative in which it is diluted.
- History (or current) seizure disorder
- Contraindications to anesthesia
- Significant cardiovascular disease (e.g. h/o hypertension, arrhythmias, myocardial infarction, congestive heart failure, congenital heart defects, coronary artery disease)
- Increased risk factors for difficult intubation and/or ventilation
Show all 19Show fewer
- Obesity (BMI>=30 kg/m2)
- Mallampati class > 2.
- History of or current obstructive sleep apnea.
- Increased risk of aspiration
- Any per oral intake within 8 hours of anesthetic exposure
- Conditions that delay gastric emptying (e.g. obesity, hiatal hernia, gastro esophageal reflux disease, pregnancy, etc.)
- Pulmonary disease (e.g. chronic obstructive pulmonary disorder, asthma requiring rescue inhaler within last month, emphysema, pulmonary hypertension, pulmonary fibrosis etc).
- Neurological disease. Patients with history of strokes, seizures, brain surgery, brain tumor, increased intracranial pressure.
- Psychiatric disease. History of or presents of psychosis, schizophrenia, schizo-affective disorder.
- Specific Medication Current Use. History of or current intake of antipsychotics or sedatives.
- Drug abuse. History of or current use of illegal drugs such as stimulants or depressants.
- Pregnancy or breastfeeding
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania, Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Study of Human Multi-Sensory Integration: A Neurophysiologic Correlate of Conscious Perception
The primary aim of this study is to determine whether spatiotemporal characteristics of multisensory evoked potentials can be used as a marker of consciousness (awareness) under anesthesia.
The secondary aim is to characterize changes in the characteristics of evoked potentials under anesthesia in both single sensory modality (visual, auditory) and across sensory modalities.
Read the detailed description
This is a prospective, dual parallel arm human subject study aimed at determining the relationship between level of sedation (consciousness) and features of multi and uni-sensory evoked potentials with the ultimate goal of developing novel means of detecting consciousness under anesthesia with potential for application to other clinical settings such as brain injury. For this purpose, the investigators have chosen two anesthetics with fundamentally distinct mechanisms of action: propofol and ketamine.
The study will involve healthy compensated volunteers. On the day of the study, an EEG cap will be applied to the participant for monitoring brain activity and an intravenous line will be placed for drug administration. Blood pressure, ECG, pulse oxymetry, and end-tidal carbon dioxide (from nasal cannula) will be monitored. Supplemental oxygen will be administered using a nasal cannula. Subjects will then perform the behavioral tasks in the awake state for approximately 1 hour.
After this phase is complete, participants will receive either propofol or ketamine (chosen permuted block randomization) using a clinician bolus/infusion strategy titrated to Richmond Agitation-Sedation Scale score of -1 (see above). Once the desired sedation level is achieved, subjects will once again complete the behavioral tasks. After the completion of this phase (approximately 1 hour) the anesthetic dose will be increased to attain Richmond Agitation-Sedation Scale -3 to -4. At this level of sedation subjects will not be able to do the behavioral task and only the evoked potentials will be recorded. Upon completion of this phase (approximately 1 hour), sedation level will be decreased to return the subject to a Richmond Agitation-Sedation Scale of -1 and once again the tasks will be repeated.
Finally, the anesthetic infusion will be stopped. Once the Richmond Agitation-Sedation Scale score of 0 is attained, participants will once again perform the behavioral task (approximately 1 hour). This will conclude the experimental phase of the trial. Subjects will be monitored until clinically established discharge criteria are met. This includes adequate respiration, blood pressure, oxygen saturation and activity level. No formal follow-up is required; however, subjects will be called 24 hours after study completion.
- Conditions
- Anesthesia Awareness
- Being tested
- Propofol, Ketamine Injectable Product
- Medical subject headings
- Intraoperative Awareness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called Diprivan
Titration of propofol to minimal and moderate sedation as measured by Richmond Agitation-Sedation Scale with behavioral task performance over several hours.
Ketamine Injectable ProductDrug
Also called Ketalar
Titration of ketamine to minimal and moderate sedation as measured by Richmond Agitation-Sedation Scale with behavioral task performance over several hours.
| Study group | Role | What they receive |
|---|---|---|
| Propofol | Experimental | Propofol sedation titrated to clinical effect as measured by Richmond Agitation-Sedation Scale. Receives: Drug: Propofol |
| Ketamine | Experimental | Ketamine sedation titrated to clinical effect as measured by Richmond Agitation-Sedation Scale. Receives: Drug: Ketamine Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multi-sensory Evoked Responses Measured using Electroencephalography
The primary study endpoint is multi-sensory evoked responses measured using EEG in units of millivolts squared per hertz at Richmond Agitation and Sedation Scale scores of 0, -1, -2, -3 and -4. Multisensory evoked responses will be compared to those evoked by each uni-sensory modality (auditory and visual) individually. Evoked responses will be assessed in the frequency domain using spectral analysis techniques which quantify power of each neuronal oscillation (e.g. alpha, delta, theta and gamma) in terms of mV^2/Hz. Analysis will be performed separately during the period before drug administration and at different levels of sedation quantified with RASS scores. The investigators will test the hypothesis that with increasing doses of intravenous anesthetics, audiovisual (multisensory) responses will approximate algebraic sum of neuronal responses elicited by visual and auditory stimuli presented separately.
Measured: 2-6 hours per subject
Secondary outcomes (1)
Single Modality Evoked Potentials
The secondary endpoint is to use EEG recordings to demonstrate changes in the characteristics of evoked potentials under anesthesia using single sensory modality (visual, auditory) and across sensory modalities. Conventional evoked potentials will be computed as average waveforms aligned with respect to stimulus onset on a channel-by-channel basis.
Measured: 2-6 hours per subject
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start30 Jul 2018
- Primary completionMay 2023 (estimated)
- Study completionMay 2023 (estimated)
Why it stopped: Due to the impact of COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anesthesia AwarenessStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Max Kelz, MD, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498391
- Sponsor's protocol ID
- 829800
- Acronym
- MSI
- Status last verified
- Feb 2023
- First submitted
- 12 Mar 2018
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Davila DG, McKinstry-Wu A, Kelz MB, Proekt A. The Administration of Ketamine Is Associated with Dose-Dependent Stabilization of Cortical Dynamics in Humans. J Neurosci. 2025 May 14;45(20):e1545242025. doi: 10.1523/JNEUROSCI.1545-24.2025.
PubMed 40204440
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Human Multi-Sensory Integration: A Neurophysiologic Correlate of Conscious Perception
- ClinicalTrials.gov ID
- NCT03498391
- Acronym / sponsor ID
- MSI / 829800
- Conditions
- Anesthesia Awareness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Due to the impact of COVID-19
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 30 Jul 2018 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 13 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this study is to determine whether spatiotemporal characteristics of multisensory evoked potentials can be used as a marker of consciousness (awareness) under anesthesia.
The secondary aim is to characterize changes in the characteristics of evoked potentials under anesthesia in both single sensory modality (visual, auditory) and across sensory modalities.
Detailed description
This is a prospective, dual parallel arm human subject study aimed at determining the relationship between level of sedation (consciousness) and features of multi and uni-sensory evoked potentials with the ultimate goal of developing novel means of detecting consciousness under anesthesia with potential for application to other clinical settings such as brain injury. For this purpose, the investigators have chosen two anesthetics with fundamentally distinct mechanisms of action: propofol and ketamine.
The study will involve healthy compensated volunteers. On the day of the study, an EEG cap will be applied to the participant for monitoring brain activity and an intravenous line will be placed for drug administration. Blood pressure, ECG, pulse oxymetry, and end-tidal carbon dioxide (from nasal cannula) will be monitored. Supplemental oxygen will be administered using a nasal cannula. Subjects will then perform the behavioral tasks in the awake state for approximately 1 hour.
After this phase is complete, participants will receive either propofol or ketamine (chosen permuted block randomization) using a clinician bolus/infusion strategy titrated to Richmond Agitation-Sedation Scale score of -1 (see above). Once the desired sedation level is achieved, subjects will once again complete the behavioral tasks. After the completion of this phase (approximately 1 hour) the anesthetic dose will be increased to attain Richmond Agitation-Sedation Scale -3 to -4. At this level of sedation subjects will not be able to do the behavioral task and only the evoked potentials will be recorded. Upon completion of this phase (approximately 1 hour), sedation level will be decreased to return the subject to a Richmond Agitation-Sedation Scale of -1 and once again the tasks will be repeated.
Finally, the anesthetic infusion will be stopped. Once the Richmond Agitation-Sedation Scale score of 0 is attained, participants will once again perform the behavioral task (approximately 1 hour). This will conclude the experimental phase of the trial. Subjects will be monitored until clinically established discharge criteria are met. This includes adequate respiration, blood pressure, oxygen saturation and activity level. No formal follow-up is required; however, subjects will be called 24 hours after study completion.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propofol | Experimental | Drug: PropofolPropofol sedation titrated to clinical effect as measured by Richmond Agitation-Sedation Scale. |
| Ketamine | Experimental | Drug: Ketamine Injectable ProductKetamine sedation titrated to clinical effect as measured by Richmond Agitation-Sedation Scale. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy volunteers ages 18-65 years old
- American Society of Anesthesiologists (ASA) Physical Status I or II (i.e. healthy)
- Body Mass Index <30 kg/m2
- Easily visible uvula
Key exclusion criteria (19 listed)
- Contraindications to administration of either propofol or ketamine
- Allergy to either one of the medications or preservative in which it is diluted.
- History (or current) seizure disorder
- Contraindications to anesthesia
- Significant cardiovascular disease (e.g. h/o hypertension, arrhythmias, myocardial infarction, congestive heart failure, congenital heart defects, coronary artery disease)
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 |
|---|---|---|
| PropofolAlso: DiprivanTitration of propofol to minimal and moderate sedation as measured by Richmond Agitation-Sedation Scale with behavioral task performance over several hours. | Drug | Propofol |
| Ketamine Injectable ProductAlso: KetalarTitration of ketamine to minimal and moderate sedation as measured by Richmond Agitation-Sedation Scale with behavioral task performance over several hours. | Drug | Ketamine |
Primary outcome
Multi-sensory Evoked Responses Measured using Electroencephalography
Time frame: 2-6 hours per subject
The primary study endpoint is multi-sensory evoked responses measured using EEG in units of millivolts squared per hertz at Richmond Agitation and Sedation Scale scores of 0, -1, -2, -3 and -4. Multisensory evoked responses will be compared to those evoked by each uni-sensory modality (auditory and visual) individually. Evoked responses will be assessed in the frequency domain using spectral analysis techniques which quantify power of each neuronal oscillation (e.g. alpha, delta, theta and gamma) in terms of mV^2/Hz. Analysis will be performed separately during the period before drug administration and at different levels of sedation quantified with RASS scores. The investigators will test the hypothesis that with increasing doses of intravenous anesthetics, audiovisual (multisensory) responses will approximate algebraic sum of neuronal responses elicited by visual and auditory stimuli presented separately.
1 secondary outcome
Single Modality Evoked Potentials
Time frame: 2-6 hours per subject
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Derived from this study: PubMed 40204440Davila DG, McKinstry-Wu A, Kelz MB, Proekt A. The Administration of Ketamine Is Associated with Dose-Dependent Stabilization of Cortical Dynamics in Humans. J Neurosci. 2025 May 14;45(20):e1545242025. doi: 10.1523/JNEUROSCI.1545-24.2025.
- Individual participant dataSharing planned: No
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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.
Max Kelz, MD, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Propofol and Ketamine Injectable Product in people with Anesthesia Awareness, run by University of Pennsylvania 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 4 inclusion and 19 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: paused, as of the sponsor's last update on 8 Feb 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Multi-sensory Evoked Responses Measured using Electroencephalography (time frame: 2-6 hours per subject). 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 NCT03498391, which also lists 1 linked publication.
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 8 Feb 2023; AzTrials last refreshed its copy on 29 Oct 2026.