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| ID | Type | Description | Link |
|---|---|---|---|
| K08GM083213 | U.S. NIH Grant/Contract | View source |
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One study drug (thiopental) became commercially unavailable
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of General Medical Sciences (NIGMS) | NIH |
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This study involves 60 healthy volunteers aged between 18 and 50 recruited from the general community. It involves doing a set of simple memory tests while inside a fMRI machine. The subject is given a very low dose of an anesthetic drug intravenously while in the scanner. The subject then sees a sequence of pictures on a screen, and presses a button if they remember seeing the picture before. While this is happening, the scanner will be capturing images that tell us what parts of the brain are active. Hypothesis: patterns of hippocampal and amygdala activation during the encoding and retrieval of memory,as measured by fMRI, will be altered by intravenous anesthetics such that suppression of hippocampal and amygdala activities will be dissociable. This dissociation pattern will be different between the drugs propofol and thiopental.
Background: Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects.
Methods: Sixty healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μgml-1, thiopental, at an estimated brain concentration of 3.0 μgml-1, or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo given in low dose to gauge subject's responses to visual stimuli. |
|
| Propofol | Active Comparator | Propofol given at 0.90 μgml-1 to gauge subject's responses to visual stimuli. |
|
| Thiopental | Active Comparator | Thiopental given at 3.0 μgml-1 to gauge subject's responses to visual stimuli. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Blood-oxygen-level-dependent Significant Activation Cluster | Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported. | for 90 minutes after the drug/placebo was commenced |
| Measure | Description | Time Frame |
|---|---|---|
| Blood-oxygen-level-dependent Significant Activation Cluster for Positive Sequential Memory | Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kane Pryor, M.D. | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medical College | New York | New York | 10065 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26174294 | Derived | Pryor KO, Root JC, Mehta M, Stern E, Pan H, Veselis RA, Silbersweig DA. Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects. Br J Anaesth. 2015 Jul;115 Suppl 1(Suppl 1):i104-i113. doi: 10.1093/bja/aev038. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo given in low dose to gauge subject's responses to visual stimuli. Placebo: A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine. |
| FG001 | Propofol | Propofol give at 0.90 μgml-1 to gauge subject's responses to visual stimuli. Propofol: A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
| FG002 | Thiopental | Thiopental give at 3.0 μgml-1 to gauge subject's responses to visual stimuli. Thiopental: A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo given in low dose to gauge subject's responses to visual stimuli. Placebo: A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine. |
| BG001 | Propofol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood-oxygen-level-dependent Significant Activation Cluster | Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported. | Of the 20 placebo subjects recruited, 3 subjects' data was excluded due to technical problems or poor quality. Of the 21 propofol subjects recruited, 3 subjects' data was excluded due to technical problems, poor quality, or subject withdrawal. Of the 19 thiopental subjects recruited, no subjects' data was excluded. | Posted | Number | BOLD significantly activated clusters | for 90 minutes after the drug/placebo was commenced |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo given in low dose to gauge subject's responses to visual stimuli. Placebo: A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kane Pryor | Weill Cornell Medicine | (212) 746-2953 | kap9009@med.cornell.edu |
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| ID | Term |
|---|---|
| D015742 | Propofol |
| D013874 | Thiopental |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Propofol | Drug | A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
|
| Thiopental | Drug | A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
|
| for 90 minutes after the drug/placebo was commenced |
| Infusion technical problems |
|
| poor subject data |
|
Propofol given at 0.90 μgml-1 to gauge subject's responses to visual stimuli. Propofol: A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
| BG002 | Thiopental | Thiopental give at 3.0 μgml-1 to gauge subject's responses to visual stimuli. Thiopental: A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Placebo given in low dose to gauge subject's responses to visual stimuli. Placebo: A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine. |
| OG001 | Propofol | Propofol give at 0.90 μgml-1 to gauge subject's responses to visual stimuli. Propofol: A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
| OG002 | Thiopental | Thiopental give at 3.0 μgml-1 to gauge subject's responses to visual stimuli. Thiopental: A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. |
|
|
| Secondary | Blood-oxygen-level-dependent Significant Activation Cluster for Positive Sequential Memory | Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported. | Of the 20 placebo subjects recruited, 3 subjects' data was excluded due to technical problems or poor quality. Of the 21 propofol subjects recruited, 3 subjects' data was excluded due to technical problems, poor quality, or subject withdrawal. Of the 19 thiopental subjects recruited, no subjects' data was excluded. | Posted | Number | BOLD significantly activated clusters | for 90 minutes after the drug/placebo was commenced |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Propofol | Propofol give at 0.90 μgml-1 to gauge subject's responses to visual stimuli. Propofol: A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. | 0 | 21 | 0 | 21 | 0 | 21 |
| EG002 | Thiopental | Thiopental give at 3.0 μgml-1 to gauge subject's responses to visual stimuli. Thiopental: A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine. | 0 | 19 | 0 | 19 | 0 | 19 |
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013858 | Thiobarbiturates |
| D001463 | Barbiturates |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Title | Measurements |
|---|---|
|
| Right Hippocampus |
|
| Left Hippocampus |
|
| Right Parahippocampal Cortex |
|
| Left Parahippocampal Cortex |
|