Ketamine and Propofol NeuroImaging

ConditionsAnesthesiaPain
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-59
SponsorKeith M Vogt

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

have none of the specific

Disqualifiers

have a valid email address and valid phone number throughout the study

free from any non-MRI compatible implants

are pregnant or attempting to conceive

body mass index (BMI) > 35

Trial design

Design model

Crossover

Treatments tested in this trial

  • Propofol

    Drug

    Subjects will receive an intravenous infusion of this drug, during portions of the study.

  • Ketamine

    Drug

    Subjects will receive an intravenous infusion of this drug, during portions of the study.

  • Peripheral Nerve Stimulation

    Device

    Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with specific experimental events.

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Propofol, followed by propofol+ketamine (given at first visit)Experimental treatment 3 interventions
Group B: Ketamine, followed by ketamine+propofol (given at first visit)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
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).
2

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).

Time frame
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 outcomes

1

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.

Time frame
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.
2

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.

Time frame
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.
3

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.

Time frame
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.
4

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.

Time frame
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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Keith M Vogt

Lead sponsor

University of Pittsburgh

Sponsor institution

National Institute of General Medical Sciences (NIGMS)

Collaborator