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| ID | Type | Description | Link |
|---|---|---|---|
| R35GM146822 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propofol, followed by propofol+ketamine (given at first visit) | Experimental |
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. |
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| Ketamine, followed by ketamine+propofol (given at first visit) | Experimental |
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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propofol | Drug | Subjects will receive an intravenous infusion of this drug, during portions of the study. |
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| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Keith M Vogt, MD, PhD | Contact | 4126473147 | kev18@pitt.edu |
| Name | Affiliation | Role |
|---|---|---|
| Keith M Vogt, MD, PhD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh | Recruiting | Pittsburgh | Pennsylvania | 15213 | United States |
De-identified data to share:
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.
Data will be shared via a publicly-accessible online platform that allows user download at no cost.
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015742 | Propofol |
| D007649 | Ketamine |
| D004561 | Transcutaneous Electric Nerve Stimulation |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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Only the ordering of drug assignments is randomized. After completing all visits, all subjects will have underwent all the same interventions.
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Participants are not informed which agent is being administered first, but do know they will receive both in each drug session.
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| Ketamine | Drug | Subjects will receive an intravenous infusion of this drug, during portions of the study. |
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| 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. |
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| 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. |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D012046 | Rehabilitation |
| D000698 | Analgesia |
| D000760 | Anesthesia and Analgesia |