Ketamine and Propofol NeuroImaging (KAPNI)

This is a multi-visit which will collect MRI (pictures of the brain) and EEG (brain waves) data to determine changes in brain connectivity and brain activity for memory formation and pain perception while receiving the commonly-used anesthetic agents ketamine and propofol, both alone and in combination.

Study Overview

• Status: Recruiting
• Conditions: Pain; Anesthesia
• Intervention / Treatment: Drug: Propofol; Drug: Ketamine; Device: Peripheral Nerve Stimulation

Detailed Description

There are four independent drug-administration sessions, visits 1, 3, 5, and 7. In all four of these sessions, both drugs are received, but in two different sequences. Two of these are EEG sessions and two are MRI sessions. Both EEG and MRI will have the same two drug orderings:

• Propofol alone, followed by ketamine and propofol together
• Ketamine alone, followed by propofol and ketamine together Assignment to propofol alone first, versus ketamine alone first will be randomized. But, all subjects will be assigned to receive both drug orderings under both EEG monitoring and MRI acquisition.

A follow-up memory testing visit will occur the day after each MRI/EEG session, on visits 2, 4, 6, and 8. No drugs are given during the next-day testing sessions.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Keith M Vogt, MD, PhD; Phone Number: 4126473147; Email: kev18@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Keith M Vogt, MD, PhD; Phone Number: 4126473147; Email: kev18@pitt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults 18-59 years of age, who:
• have none of the specific exclusion criteria
• have a valid email address and valid phone number throughout the study
• free from any non-MRI compatible implants

Exclusion Criteria:

• are pregnant or attempting to conceive
• body mass index (BMI) > 35
• significant memory impairment or hearing loss
• sleep apnea
• chronic pain or frequently taking pain medication
• chronic medical conditions requiring treatment (hypertension, diabetes, high cholesterol)
• neurologic disease, including seizures and tremor
• psychiatric diagnoses, including anxiety, depression, panic, or PTSD
• a history of any of these medical conditions: abnormal heartbeats (cardiac conduction abnormality or arrhythmia), liver or kidney disease, or significant lung disease
• severe claustrophobia or intolerance of an MRI
• have metal implants or non-removable metal piercings
• having a history of adverse reaction to ketamine or propofol
• daily alcohol or heavy alcohol use; history of alcohol abuse
• current daily smoker
• regular or recent marijuana use (including prescribed/medical marijuana)
• illicit drug use, i.e., street drugs
• regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propofol, followed by propofol+ketamine (given at first visit); Propofol, followed by propofol+ketamine at Visit 1; Ketamine, followed by ketamine+propofol at Visit 3; Propofol, followed by propofol+ketamine at Visit 5; Ketamine, followed by ketamine+propofol at Visit 7 EEG will be done at either visits 1 and 3 or 5 and 7; fMRI will be done at the other two (non-EEG) visits.	Drug: Propofol; Subjects will receive an intravenous infusion of this drug, during portions of the study.; Other Names: Diprivan; Drug: Ketamine; Subjects will receive an intravenous infusion of this drug, during portions of the study.; Other Names: ketalar; Device: Peripheral Nerve Stimulation; Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with specific experimental events.; Other Names: electric nerve stimulation
Experimental: Ketamine, followed by ketamine+propofol (given at first visit); Ketamine, followed by ketamine+propofol at Visit 1; Propofol, followed by propofol+ketamine at Visit 3; Ketamine, followed by ketamine+propofol at Visit 5; Propofol, followed by propofol+ketamine at Visit 7 EEG will be done at either visits 1 and 3 or 5 and 7; fMRI will be done at the other two (non-EEG) visits.	Drug: Propofol; Subjects will receive an intravenous infusion of this drug, during portions of the study.; Other Names: Diprivan; Drug: Ketamine; Subjects will receive an intravenous infusion of this drug, during portions of the study.; Other Names: ketalar; Device: Peripheral Nerve Stimulation; Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with specific experimental events.; Other Names: electric nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explicit Memory Performance, comparing single-drug to drug-combination condition	Recognition memory testing, using the Remember-Know procedure, in which subjects indicate whether they recognize previously experienced experimental items among novel items (not previously in the experiment). This allows calculation of interdependent measures of recollection & familiarity using the signal detection statistic, d'. d' is calculated as the cumulative Gaussian distribution of false positive responses subtracted from the cumulative Gaussian distribution of correctly identified previously-experienced items. d' is on a (theoretically infinite) scale of standard deviation units, with negative values representing performance worse than chance guessing and positive values representing stand deviations of performance above chance.	Visits 2, 4, 6, and 8. Visits spaced at least 1 week apart, are 1 hour in length, and are 12-36 hours after the preceding visit (1, 3, 5, and 7).
Pain intensity and unpleasantness ratings, comparing single-drug to drug-combination condition	Numerical rating scale (0-10) pain score difference, comparing the single-drug condition to the steady-state dose of the drug-combination condition. Higher pain scores indicate more pain; a positive difference between pain scores during the single-drug condition minus the value during the steady-state dose of the combination-drug condition indicates pain reduction (a better outcome).	Visits 1, 3, 5, and 7: immediately following each experimental condition. These visits are 3 hours in length and spaced at least 1 week apart.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI-based activation during memory formation, comparing the single-drug condition to the combination-drug condition	The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate a larger difference in brain activity, with positive values indicating decreases under the combination-drug condition, while negative Z-scores indicate increases under the combination-drug condition, compared to the single-drug condition. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.	MRI visits (1 and 3, or 5 and 7), which are are 3 hours in length and spaced at least 1 week apart. Data collected at 3 timepoints in 8-minute MRI scans: at baseline, under one drug, and under both drugs.
MRI-based activation during painful stimulation, comparing the single-drug condition to the combination-drug condition	The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate a larger difference in brain activity, with positive values indicating decreases under the combination-drug condition, while negative Z-scores indicate increases under the combination-drug condition, compared to the single-drug conditions. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.	MRI visits (1 and 3, or 5 and 7), which are are 3 hours in length and spaced at least 1 week apart. Data collected at 3 timepoints in 8-minute MRI scans: at baseline, under one drug, and under both drugs.
MRI-based changes in functional connectivity, comparing the single-drug condition to the combination-drug condition	Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between single-drug and combination-drug conditions. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the single-drug condition, and more negative scores mean stronger connectivity with the combination-drug condition. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.	MRI visits (1 and 3, or 5 and 7), which are are 3 hours in length and spaced at least 1 week apart. Data collected at 3 timepoints in 8-minute MRI scans: at baseline, under one drug, and under both drugs.
EEG-based changes in functional connectivity, comparing single-drug to combination-drug condition.	Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between single-drug and combination-drug conditions. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the single-drug condition, and more negative scores mean stronger connectivity with the combination-drug condition. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.	EEG visits (1 and 3, or 5 and 7), which are are 3 hours in length and spaced at least 1 week apart. Data collected at 3 timepoints in 8-minute EEG scans: at baseline, under one drug, and under both drugs.

Collaborators and Investigators

• Sponsor: Keith M Vogt
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Keith M Vogt, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 2, 2028

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: functional MRI; Ketamine; Propofol; sedation; functional connectivity; electric nerve stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Organic Chemicals; Therapeutics; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Physical Therapy Modalities; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Rehabilitation; Anesthesia and Analgesia; Electric Stimulation Therapy; Analgesia; Propofol; Ketamine; Transcutaneous Electric Nerve Stimulation
• Other Study ID Numbers: STUDY25110029; R35GM146822 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified data to share:

• age, height, weight, sex
• survey results quantifying pain predispositions (catastrophizing, vigilance & anxiety), depression, anxiety, stress, and sleep
• pain intensity & unpleasantness ratings
• observer assessment of sedation ratings
• Behavioral performance data for long-term memory
• structural and functional MRI images

• IPD Sharing Time Frame: After analysis is complete and results have been published, all the above data will be shared in de-identified format, linked together by an assigned subject number.
• IPD Sharing Access Criteria: Data will be shared via a publicly-accessible online platform that allows user download at no cost.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• 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.: No