This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes (NCT00504894), a randomized phase 4 study. The primary outcome is Blood-oxygen-level-dependent Significant Activation Cluster.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00504894 |
| Phase | Phase 4 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Weill Medical College of Cornell University |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers aged between 18 and 50, recruited from the general community. The registry describes 60 volunteers and reports arm-specific recruitment and exclusions for the primary outcome.
Intervention
Intravenous propofol at 0.90 μgml-1 or thiopental at 3.0 μgml-1, administered during memory testing in an fMRI scanner.
Comparator
Placebo, described as a low dose used to gauge responses to visual stimuli.
Primary question
Whether drug or placebo exposure is associated with significantly activated BOLD clusters during the 90 minutes after administration, in hypothesized brain regions and elsewhere.
The study focused on memory processes involving the amygdala and hippocampus. Participants viewed pictures and responded when they remembered seeing a picture before; fMRI recorded brain activity during the task. The stated hypothesis was that intravenous anesthetics would alter hippocampal and amygdala activation during memory encoding and retrieval, with dissociable suppression patterns and a difference between propofol and thiopental.
The registry names an additional outcome, BOLD Significant Activation Cluster for Positive Sequential Memory. It does not report outcome values, treatment comparisons, effect estimates or analysis results. The central question can therefore be described from the study rationale and endpoint definition, but the registry record does not establish whether the hypothesized patterns were observed.
3. Trial Design
This was a Phase 4, randomized, single-masked, parallel study. The registry lists placebo, propofol and thiopental as drug interventions. It records enrollment of 60 and identifies healthy volunteers as the study population. The start is recorded as 2007-03 and primary completion as 2013-11; the current status is terminated.
The brief summary describes volunteers performing memory tests while inside an fMRI scanner. They viewed a sequence of pictures and pressed a button when they remembered a picture. The interventions were administered intravenously during scanning. The placebo arm is described as receiving a low dose, and the active arms list propofol at 0.90 μgml-1 and thiopental at 3.0 μgml-1. The registry does not specify the meaning or implementation of single masking, so it is not possible to identify which people involved in the study were masked.
For the primary outcome, the record says data from 3 placebo subjects were excluded because of technical problems or poor quality. It says data from 3 propofol subjects were excluded because of technical problems, poor quality or subject withdrawal. The corresponding description for thiopental ends after stating that no subjects’ data were excluded; the remainder of that entry is not reported in the registry record. These are outcome-population details, not a complete account of every analysis population.
The registry marks the study as terminated, but the reason for termination is not reported in the registry record. It does not report the recruitment timeline beyond the start and primary-completion entries, nor does it describe the allocation procedure, masking procedures, adherence, or study conduct in enough detail to assess them. The record identifies no analysis results. Its design and rationale can be described, but the available record does not support an assessment of treatment effects.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Placebo | Propofol | Thiopental |
|---|---|---|---|
| STARTED | 20 | 21 | 19 |
| COMPLETED | 17 | 18 | 19 |
| NOT COMPLETED | 3 | 3 | 0 |
Reasons for not completing this period:
| Reason | Placebo | Propofol | Thiopental |
|---|---|---|---|
| fMRI technical problems | 1 | 1 | 0 |
| Withdrawal by Subject | 0 | 1 | 0 |
| Infusion technical problems | 0 | 1 | 0 |
| poor subject data | 2 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: 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.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Placebo | Propofol | Thiopental | Total |
|---|---|---|---|---|---|
| Participants analysed | 20 | 21 | 19 | 60 | |
| Age, Continuous | years | 26 (22 to 29) | 25 (23 to 26) | 24 (22 to 32.5) | 25 (22 to 28) |
| Sex: Female, Male: Female | Participants | 15 | 14 | 13 | 42 |
| Sex: Female, Male: Male | Participants | 5 | 7 | 6 | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Blood-oxygen-level-dependent Significant Activation Cluster, measured over for 90 minutes after the drug/placebo was commenced.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | BOLD significantly activated clusters |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts BOLD significantly activated clusters during the 90 minutes after the drug or placebo was commenced. BOLD, or blood-oxygen-level-dependent, fMRI is a signal used to assess changes in brain activity. A cluster is a group of neighboring voxels meeting the specified significance criteria; the registry says clusters containing voxel maxima at the stated thresholds are reported.
The endpoint description identifies three anatomical regions selected because of an a priori mechanistic hypothesis: the amygdala, hippocampus and parahippocampus, each assessed bilaterally. It also describes a significance approach for non-hypothesized regions outside the medial temporal lobe. The endpoint is therefore intended to identify where statistically significant activation clusters occur, rather than to provide a direct behavioral measure of memory performance or a single overall measure of memory.
Counting clusters can help describe the location of statistically detected fMRI signals under specified thresholds. It does not, by itself, indicate the magnitude or clinical importance of an effect. Interpretation also depends on the analysis choices, imaging data quality, and the number and characteristics of clusters detected. The registry record does not report the observed cluster counts, their locations, or treatment comparisons, so the measured endpoint cannot be interpreted as a result for any intervention.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a mechanistic imaging study: volunteers performed a picture-recognition task while fMRI recorded brain activity after intravenous placebo, propofol or thiopental. Its stated hypothesis concerns changes in activation associated with memory encoding and retrieval, particularly in the amygdala and hippocampus, and whether patterns differ between the active drugs.
The primary outcome is a count of significantly activated BOLD clusters under specified statistical thresholds. The registry gives the criteria for declaring clusters significant, but it does not give the cluster counts, locations, estimates, uncertainty intervals, p-values from observed comparisons, or arm-level outcome data. The analysis count is recorded as 0. Consequently, no direction, size or precision of an outcome difference can be described from this record. Missing outcome results should not be interpreted as evidence that the interventions had identical effects, that no activation occurred, or that the hypothesis was disproved.
The registry reports recruitment and data exclusions for the primary outcome. It records 20 placebo subjects recruited, with 3 excluded for technical problems or poor quality; 21 propofol subjects recruited, with 3 excluded for technical problems, poor quality or subject withdrawal; and 19 thiopental subjects recruited, with no subjects’ data excluded before the entry cuts off. These figures describe the registry’s account of the primary-outcome population, not the number contributing to a reported treatment comparison. The full thiopental description and the exact analysis populations are not reported in the registry record.
The study is marked terminated. The registry record does not report why it was terminated, whether the study ended as planned, or whether outcome reporting was incomplete. It also does not report an analysis plan, the handling of missing data, or any estimates adjusted for covariates. Thus, the recorded design and threshold rules offer context for how imaging results might have been evaluated, but they cannot substitute for observed results.
For readers assessing evidence, the key distinction is between an endpoint definition and an endpoint finding. The former is present: the record defines a count of significant clusters and describes regional correction procedures. The latter is absent: no cluster results or statistical comparisons are reported. There is therefore no basis in this record to judge whether the hypothesized activation patterns appeared, how precisely they were estimated, or whether the active interventions differed from placebo or from each other.
Similarly, the absence of posted efficacy analyses does not settle whether the study generated data or whether those data were analyzed outside the registry. Such information is not reported in the registry record. The defensible interpretation is limited to the documented aims, design, outcome definition and participant-flow details, with no treatment-effect conclusion.
9. Statistical Methods Explained
The registry gives an imaging endpoint and criteria for determining whether activation clusters meet a statistical significance threshold. It does not report an analysis plan or results. The distinction matters: a threshold describes a rule for classifying findings, while an estimate and its uncertainty describe what the data indicate under an analysis.
What does a BOLD cluster represent?
In general, fMRI measures changes in the blood-oxygen-level-dependent signal as an indirect indicator of brain activity. An analysis tests signal patterns across voxels, which are small units in an image. Nearby voxels meeting the relevant criteria may be grouped into a cluster. Cluster locations can help describe where a signal was detected, but a cluster count is not itself a measure of how large or important the underlying biological response is. The registry defines the primary outcome as the number of significantly activated clusters and says clusters containing voxel maxima at the specified thresholds are reported.
The endpoint is assessed during the 90 minutes after the drug or placebo was commenced. The record identifies the amygdala, hippocampus and parahippocampus bilaterally as regions with an a priori mechanistic hypothesis. In general, defining regions in advance can focus tests on questions motivated by the study hypothesis. The record also describes a separate significance criterion for non-hypothesized regions outside the medial temporal lobe.
Why are there multiple thresholds?
The registry describes single-tailed t tests. For hypothesized regions, a voxel-wise P value first had to be < 0.001 without correction, followed by a P value < 0.05 after family-wise error correction within the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, the same initial uncorrected voxel-wise criterion was followed by a P value < 0.05 after family-wise error correction across the whole brain.
In general, testing many voxels creates many opportunities for apparently unusual results to arise by chance. Family-wise error correction addresses the chance of at least one false positive across a defined family of tests. The relevant family differs in the registry description: the hypothesized anatomical region for the a priori tests, and the whole brain for non-hypothesized regions outside the medial temporal lobe. Correction can make a criterion more stringent, so the scope of the correction is important when interpreting a reported finding.
An uncorrected voxel-wise threshold and a corrected threshold serve different roles in this description. The initial criterion identifies voxel maxima for further consideration; the corrected criterion addresses multiplicity in the relevant region or across the whole brain. Passing a threshold indicates statistical evidence under the specified procedure. It does not quantify the size of a signal, establish its reproducibility, or prove a biological mechanism.
What does a single-tailed test imply?
In general, a single-tailed test evaluates evidence in a specified direction rather than treating departures in either direction symmetrically. That choice depends on a justified directional hypothesis and should be set before examining results. The registry states that single-tailed t tests were used, but it does not report the directional hypotheses for individual tests or a full statistical analysis plan. The threshold description alone is not enough to reconstruct every test or determine whether the procedure was applied as intended.
What can the record establish about the analysis?
The record names the endpoint, time window, anatomical regions and significance criteria. It does not report the observed number of clusters, treatment contrasts, test statistics, confidence intervals, or analysis findings. It records 0 analyses. Thus, no result can be checked against the described thresholds, and no estimate can be interpreted for magnitude or precision.
In general, confidence intervals communicate the range of effect estimates compatible with a statistical model and its assumptions. They are useful alongside point estimates because a threshold-based finding alone does not reveal precision. No confidence intervals are reported in the registry record. Nor are the model details, covariate adjustments, participant-level analysis rules, missing-data procedures, or any interim analyses reported in the registry record. Those details should not be inferred from the imaging endpoint description.
The record includes a sample-size planning assumption statement describing a generic illustration based on an observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation. It does not provide a trial-specific sample-size justification or report sample-size illustration results in the registry record for this account. Such planning illustrations, when available, are not observed power and cannot replace estimates and uncertainty from analyzed data.
10. Multiplicity, Missing Data and Analysis Populations
The registry recognizes multiplicity in its endpoint description by specifying family-wise error correction. For the a priori hypothesized regions—the bilateral amygdala, hippocampus and parahippocampus—the record describes correction within the hypothesized anatomical region after an initial uncorrected voxel-wise criterion of P < 0.001. It gives a corrected threshold of P < 0.05. For non-hypothesized regions outside the medial temporal lobe, it describes correction across the whole brain, also following an initial uncorrected voxel-wise criterion of P < 0.001 and using a corrected threshold of P < 0.05.
These stated procedures do not tell readers how many tests or contrasts were ultimately conducted, whether other outcomes or time points were tested, or how any additional multiplicity was handled. The registry record does not report a full statistical plan, analysis results, or an account of interim analyses. It records 0 analyses, so it is not possible to assess the implementation of the stated correction procedures.
The primary-outcome description reports exclusions for technical problems, poor quality and, in the propofol arm, subject withdrawal. It does not report the full analysis populations, the missing-data strategy, or whether exclusions were determined before outcome data were examined. The thiopental population description is incomplete in the registry record. The record therefore does not permit assessment of whether missingness could have affected comparisons or whether analyses included all randomized participants.
In general, exclusions and missing outcome data can affect interpretation when the chance of having usable data differs across groups or relates to the measured outcome. That is a general statistical concern, not a finding about this study. The registry’s reported reasons are not enough to determine the effect of missingness. The analysis population and sensitivity analyses are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 0 | 20 | 0.0% |
| Propofol | 0 | 21 | 0.0% |
| Thiopental | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 20 |
| Propofol | 0 of 21 |
| Thiopental | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 0 of 20 |
| Propofol | 0 of 21 |
| Thiopental | 0 of 19 |
The adverse-event entries list 0 serious adverse events, 0 other adverse events and 0 deaths for placebo, propofol and thiopental. The entries also record the numbers at risk as 20 for placebo, 21 for propofol and 19 for thiopental for both serious and other adverse events. These are the registry’s reported counts; they should be read as recorded entries, not as proof that no event occurred outside the information captured in the record.
The record does not list serious adverse-event terms. It does not provide event descriptions, severity details, timing, attribution to an intervention, or a narrative explaining how events were collected and reported. The registry record therefore supports only a description of the posted counts, not a broader safety comparison or a conclusion about risk. A zero count in a posted entry does not establish that an intervention is free of adverse effects.
These safety figures are separate from the primary imaging endpoint. They do not address whether the interventions altered BOLD activation or memory-task performance, and they do not resolve the study’s stated mechanistic hypothesis.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized imaging study of healthy volunteers performing a visual memory task during fMRI after placebo, propofol or thiopental. Its mechanistic question concerns activation patterns associated with memory processing, particularly in the amygdala and hippocampus, and whether patterns differ between the active drugs. The primary endpoint is a count of BOLD activation clusters assessed under specified significance criteria.
What the record establishes is the study’s stated rationale, broad design, interventions, endpoint definition, analysis thresholds, selected participant exclusions and posted adverse-event counts. It also records the study as terminated. These registry entries make it possible to understand what the investigators set out to examine and some of the rules they described for assessing imaging findings.
What the registry does not establish is whether any intervention changed brain activation, whether any between-group difference was observed, or how large or precise an effect might have been. No endpoint results, treatment-effect estimates, confidence intervals or analysis findings are reported, and the analysis count is recorded as 0. The missing results cannot be interpreted as a null result. They also cannot confirm the stated hypothesis.
The endpoint has a specific statistical meaning: it counts clusters that meet criteria for significance. It is not, by itself, a direct measure of memory ability, a measure of clinical benefit, or proof of a mechanism. In general, imaging findings depend on data quality and analytic choices, including voxel-wise testing, region definitions and multiplicity correction. The record describes some of those choices but does not provide enough information to evaluate how they were implemented.
The study population is described as healthy volunteers aged between 18 and 50. Its findings, if reported elsewhere, would need to be interpreted in relation to that population and the experimental memory task. The registry entry alone does not support extrapolation to other populations or settings. Nor do the posted zero adverse-event counts establish an absence of risk; they describe only the recorded entries.
The most accurate conclusion from the registry record is therefore about evidence availability: it documents a planned and conducted randomized study, but does not provide the outcome analyses needed to estimate or judge the effects under study. No treatment recommendation or efficacy conclusion follows from the record.
13. Why This Trial Matters Statistically
This trial illustrates a distinction central to statistical interpretation: a precise endpoint definition is not the same as a reported result. The registry describes a count of significantly activated BOLD clusters, the task and observation window, anatomically motivated regions, and thresholds for assessing findings. Those details help readers understand what investigators intended to measure and how statistical significance was to be defined.
Imaging studies can involve testing signal across many voxels and examining multiple brain regions. In general, the more tests performed, the greater the opportunity for chance findings unless multiplicity is addressed. The registry’s description of family-wise error correction makes the scope of correction visible: hypothesized anatomical regions for the a priori tests and the whole brain for non-hypothesized regions outside the medial temporal lobe. This is relevant context, but it cannot establish that the procedure was correctly implemented or reveal what it found.
The study also makes clear why statistical significance and scientific interpretation should be kept separate. A cluster meeting a threshold would be a statistically classified imaging finding; it would not automatically quantify the size of a response, its precision, its importance for memory, or its clinical relevance. Estimates and uncertainty, along with sufficient analysis detail, are needed for those judgments. The registry record does not report them.
Finally, the status and absence of analyses matter for evidence synthesis. The design, recruitment and outcome definitions can inform readers about the question studied, but an effect cannot be included or interpreted from a record that reports no outcome comparison. The appropriate statistical reading is to distinguish documented methods from unavailable results, rather than treating the absence of a posted finding as evidence of no effect.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this specific record is the absence of reported primary or secondary outcome results. The registry describes the endpoint and significance criteria but gives no cluster counts, effect estimates, treatment comparisons, confidence intervals or analysis findings. It records 0 analyses. As a result, the study’s stated hypothesis cannot be evaluated from this record.
The status is terminated, but the reason for termination is not reported in the registry record. The record does not say whether termination was administrative, related to recruitment or data quality, or for another reason; none should be inferred. It also does not report whether all collected data were analyzed or whether results were reported elsewhere.
Participant-flow information for the primary outcome is incomplete. The placebo and propofol exclusions are described with reasons, but the thiopental entry ends after stating that no subjects’ data were excluded. The complete analysis populations, reasons for any other missing data, and methods for handling missing outcomes are not reported in the registry record. Without those details, it is not possible to assess the effect of exclusions on comparisons.
The record specifies single masking but does not identify who was masked or how masking was maintained. It does not report the allocation procedure, complete analysis plan, model specification, covariate handling, interim analyses, or any sensitivity analyses. A trial-specific sample-size justification is not reported in the registry record.
Finally, the primary outcome is an imaging cluster count based on stated thresholds. The record does not provide the underlying signal estimates or enough analysis detail to assess robustness, magnitude, or precision. These limitations do not show that the study was conducted improperly; they define what can and cannot be concluded from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes — NCT00504894.
- Registry record last updated 2021-07-15; status last verified 2021-06.
- Results first posted 2017-05-18.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00504894 is a Phase 4 randomized, single-masked, parallel study listed as terminated. It enrolled 60 healthy volunteers aged between 18 and 50 and compared placebo with intravenous propofol at 0.90 μgml-1 and thiopental at 3.0 μgml-1 during memory testing in an fMRI scanner. The primary endpoint was the number of significantly activated BOLD clusters during the 90 minutes after administration.
The record describes a priori anatomical regions and family-wise error correction criteria. It reports some exclusions from the primary-outcome population and zero serious adverse events, other adverse events and deaths in each listed group. It does not report outcome results, treatment-effect estimates, confidence intervals or analysis findings; the analysis count is 0. The reason for termination and a complete account of analysis populations are not reported in the registry record.