Neural Correlates of Lidocaine Analgesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neural Correlates of Lidocaine Analgesia (NCT05501600), a na phase 1 study. The primary outcome is Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition.

2. Clinical Question

The broader study purpose was to characterize lidocaine’s effects on pain processing and cognitive function. Secondary outcomes include differences in pain intensity, memory performance, and motor response time between conditions. These outcomes make the research question broader than the primary brain-activation measure, but the registry record does not report their numerical results in the registry record. The clinical question is therefore about changes across experimental conditions, rather than whether lidocaine is superior to a separately assigned control treatment.

3. Trial Design

The registry identifies this as a completed phase I study, with a single-group model and allocation listed as not applicable. Masking is listed as none. The study was registered as NCT05501600 and sponsored by Keith M Vogt. The listed study dates are a start date of 2022-11-22 and a primary completion date of 2023-11-17. Registry enrollment is 30.

The study description specifies one visit and no long-term follow-up. Participants received lidocaine during the drug portion of the experiment. The listed interventions are intravenous lidocaine and peripheral nerve stimulation. The primary outcome compares the drug-free condition with the lidocaine condition, so the contrast concerns conditions within the experiment rather than separately randomized arms. The record does not describe the order of those conditions, whether their order was randomized, or any washout procedure.

Functional MRI was used to examine the brain response to painful stimulation and to identify neural correlates of pain processing and cognitive function. The primary measure is listed for the right insula, while the description says similar scores were calculated throughout the brain. The registry also lists secondary outcomes concerning pain intensity, memory performance, and motor response time. There are 5 outcome measures and 2 analyses listed, but the registry record does not report enough detail to determine the full relationship between those measures and analyses.

A single-group design can describe within-experiment condition contrasts, but it does not provide the protections of a randomized, masked comparison between treatment groups. In particular, allocation is not applicable and masking is none. The record does not report a sample-size justification, a detailed statistical analysis plan, or the procedures used to handle possible order or carryover effects. Those details should not be inferred from the phase designation, enrollment, or outcome descriptions.

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

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.

Population: Completed participants

6. Primary Endpoint

The registry lists the primary outcome as Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition, measured over 4.5 minutes.

The primary endpoint is titled as the difference in brain activation to painful stimulation between the drug-free condition and the lidocaine condition. It is listed for the right insula, with a timeframe of 4.5 minutes. The measure is a Z-score calculated using linear regression of task timing against the MRI signal time-course at each voxel, a single data point in the brain. The MRI signal is in arbitrary units and has no stated maximum or minimum.

In the registry’s description, a Z-score of 0 indicates no task-related change. Values farther from zero indicate a stronger relationship between functional MRI signal change and task timing. A positive value indicates an increase in the fMRI signal; a negative value indicates a decrease. Thus, the sign describes the direction of the task-related signal pattern, while distance from zero describes its strength in this scoring framework.

This measure is used to characterize brain response associated with the task, rather than to measure pain intensity directly. The registry states that the primary outcome is reported as a single number calculated from data across subjects combined into an overall measure of the signal difference between the conditions. It also states that dispersion measures cannot be calculated for this summary Z-score. The numerical endpoint result is not reported in the registry record. Consequently, the listed outcome definition explains what the score is intended to represent, but does not establish the observed difference or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint uses a task-related Z-score from functional MRI. The registry describes the calculation as a linear regression of task timing against the MRI signal time-course at each voxel. In general, regression estimates how an outcome varies in relation to one or more explanatory variables. Here, task timing is related to the changing signal over the scan, and the reported score represents the standardized strength and direction of that relationship as described in the registry.

What does the Z-score represent?

The registry gives a direct interpretation: a score of 0 indicates no task-related change; values farther from zero indicate a stronger relationship between the MRI signal change and task timing. Positive values indicate increases in fMRI signal, and negative values indicate decreases. The score is not a direct measure of pain intensity, and the registry notes that the MRI signal is in arbitrary units with no maximum or minimum. It is therefore important not to interpret the score as a bounded percentage or as a direct clinical scale.

The primary outcome is described as a summary number calculated from data across subjects combined into an overall statistical measure of the signal difference between the two conditions. The primary location listed is the right insula, although the description says similar scores are calculated throughout the brain. The numerical value for the primary outcome is not reported in the registry record. The score’s definition alone does not show whether the observed contrast favored either condition or how large it was.

Why does uncertainty matter?

A point estimate describes the estimated value of an effect or contrast. A confidence interval is a general statistical tool that shows a range of values compatible with the observed data under specified assumptions. It helps readers judge whether an estimate is precise or uncertain. The registry description says dispersion measures cannot be calculated for the summary Z-score. No interval or other uncertainty measure for the primary outcome is reported in the registry record. Therefore, statistical precision cannot be evaluated from the listed outcome definition.

For many outcomes, variability among observations can be estimated and used to quantify uncertainty. For this combined summary score, the record specifically cautions that dispersion measures cannot be calculated. This means readers should not assume that a conventional confidence interval or participant-level spread accompanies the posted summary. It also means the outcome’s interpretation depends on the stated construction of the overall measure, rather than on a reported distribution of individual participant scores.

What can a condition contrast establish?

The endpoint compares the drug-free condition minus the lidocaine condition. This is not described as a comparison between randomized groups: the study is listed as single-group, and allocation is not applicable. A within-experiment contrast can characterize differences between the named conditions, but interpretation may depend on how conditions were ordered and conducted. The registry record does not report condition order, randomization of order, or procedures addressing carryover. These details cannot be assumed.

More generally, masking can reduce the chance that knowledge of an assigned treatment affects participant behavior or outcome assessment. The registry lists masking as none. That design feature is relevant to interpretation, although the primary endpoint is an MRI-derived signal measure and the record does not detail image processing or assessment procedures. The record does not report whether analysts were blinded to condition labels.

How should planning illustrations be read?

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, not the trial’s original design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. These are assumptions for an illustration, not a report of the study’s design rationale. The record does not report a sample-size justification for the actual single-group study. Such illustrations are planning quantities and should not be described as observed power.

The stated illustration assumptions also do not change the study’s single-group structure. Equal allocation between two arms is an assumption used for the illustration, not evidence that the trial enrolled randomized arms. Since the numerical primary effect is not reported in the registry entries, and no planning output values are included in those details, no numerical planning result can be interpreted.

The record lists 5 outcome measures and 2 analyses. In general, when multiple outcomes or analyses are considered, the chance of obtaining at least one apparently notable result can increase unless the analysis strategy accounts for multiplicity. The registry entries do not state whether any adjustment was used, how the analyses were specified, or which outcomes were included in each analysis. This is a limitation on how fully the statistical approach can be reconstructed, not proof that an adjustment was or was not performed.

Finally, the registry lists enrollment of 30, while the serious-adverse-event entry has a risk denominator of 27. These figures refer to different registry information and should not be conflated. The enrollment figure does not establish the number analyzed for the imaging endpoint, and the risk denominator for adverse-event reporting does not establish the endpoint analysis population. The registry record does not report the analysis population or the handling of missing endpoint data.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and 2 analyses. It identifies a primary endpoint and names secondary outcomes concerning pain intensity, memory performance, and motor response time. The record does not report how all outcome measures map to the two analyses, whether additional outcomes were considered, or whether the analyses were prespecified in a detailed statistical plan.

Multiplicity refers, in general, to the statistical issue created when several outcomes, contrasts, or analyses are examined. If each is assessed separately, the overall chance of a nominally notable finding can rise. Common approaches include defining a testing hierarchy or adjusting significance thresholds, but the registry record does not report whether any multiplicity procedure was used. No conclusion about adjustment should be inferred from the number of listed outcomes or analyses alone.

The record does not report the analysis population for the primary endpoint, the number of participants with usable MRI data, or how missing or unusable measurements were handled. It also does not report whether participants were excluded from particular analyses or how incomplete secondary outcomes were treated. The enrollment entry of 30 describes registry enrollment, but it does not establish the number included in each analysis.

For the primary summary Z-score, the record says dispersion measures cannot be calculated. It does not report a confidence interval or another measure of uncertainty. The record also does not describe interim analyses, a detailed statistical analysis plan, or a sample-size justification. These omissions limit assessment of how the reported analyses were selected and how robust their interpretation would be to missing data or multiple testing.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious-adverse-event entry lists the Lidocaine group with 27 participants at risk and 0 participants affected by serious adverse events. Deaths are listed as 0. The record lists no top serious adverse-event terms. These are registry counts, not a complete description of every possible symptom or adverse event.

The separate other-adverse-event entry also lists 27 participants at risk and 0 affected. The entries should be read as the reported counts for the listed categories and group. They do not establish that every enrolled participant was included in safety follow-up, since registry enrollment is 30 and the safety risk denominator is 27. The registry record does not explain that difference, so it should not be reconciled by assumption.

A zero count in a registry entry means that no affected participants were recorded for that category in the stated group and risk set. It does not prove that no adverse events occurred outside the recorded category, that every participant had complete observation, or that risk is absent. The record does not provide additional detail about adverse-event collection, duration of safety monitoring, or event definitions. The study description specifies one visit and no long-term follow-up, which limits what can be inferred about events beyond the recorded observation period.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a phase I, single-group study was conducted to examine intravenous lidocaine in relation to pain processing and cognitive function. It describes functional MRI assessment and identifies a primary contrast between drug-free and lidocaine conditions. It also names secondary outcomes involving pain intensity, memory performance, and motor response time. The record’s primary endpoint description makes clear how the Z-score is constructed and how its sign and distance from zero are intended to be interpreted.

It does not, however, report the numerical primary outcome result. As a result, the record cannot support a statement about the observed size or direction of the brain-activation contrast. Nor does it report a confidence interval or another uncertainty measure that would show how precisely the contrast was estimated. Secondary outcome values are also not reported in the registry entries. The absence of numerical results in the record should not be mistaken for a finding of no difference.

The design context matters. This is not listed as a randomized, masked comparison of treatment groups. It is a single-group study with no masking, and the primary contrast is between experimental conditions. The registry does not report the order of the conditions or whether order was randomized. Consequently, the record alone cannot show whether a condition difference can be separated from possible order or repeated-task effects.

The outcome is a brain-signal measure rather than a direct clinical measure of pain experience. The registry separately lists pain intensity as a secondary outcome, but its result is not available in the record details. Thus, the primary endpoint description should not be taken as evidence of a change in pain intensity, memory, motor response, or clinical benefit.

The safety counts report no participants affected by recorded serious adverse events in the listed risk group, and no deaths. Those counts are limited to the reported categories and observation information; they do not establish the absence of all adverse events or longer-term risks. Overall, the record describes the research question and methods at a broad level, but does not include the outcome data needed to determine what the observed effects were or how precisely they were estimated.

13. Why This Trial Matters Statistically

This study is statistically interesting because it connects a clearly described experimental contrast with an imaging-derived endpoint. The registry explains that the score relates task timing to the MRI signal time-course and gives a directional interpretation for positive, negative, and zero values. This helps distinguish a brain-signal measure from clinical outcomes such as pain ratings or cognitive performance.

The design also illustrates why the comparison structure needs to be read carefully. The primary outcome uses drug-free and lidocaine conditions, but the registry describes a single-group study, with allocation not applicable and no masking. The contrast is not a randomized between-group estimate. Understanding that distinction prevents the condition comparison from being overinterpreted as though treatment assignment had been randomized across separate groups.

The record highlights an important reporting issue: a detailed endpoint definition is not the same as a reported result. Although the score’s construction and interpretation are described, the numerical primary result and its uncertainty are not reported in the registry entries. Without them, readers cannot assess the size, direction, or precision of the observed contrast. This is especially consequential for a summary measure that the record says has no calculable dispersion measures.

The listed secondary outcomes and the counts of outcome measures and analyses also raise questions about multiplicity and analysis specification. Those questions cannot be resolved from the registry information available. More complete reporting of analysis populations, missing-data handling, condition order, uncertainty, and the relation between outcomes and analyses would make the statistical evidence easier to evaluate.

The study therefore matters as an example of the gap that can exist between a well-described measurement concept and a fully interpretable results record. Statistical interpretation requires not only knowing what was measured, but also seeing the estimate, its uncertainty, and the analysis context.

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 primary limitation for interpreting the outcome is that its numerical result is not reported in the registry record. No uncertainty estimate is reported either, and the endpoint description says dispersion measures cannot be calculated for the combined summary Z-score. The record therefore does not permit assessment of the observed direction, size, or precision of the primary contrast.

The study is listed as single-group, with allocation not applicable and masking none. The comparison is between drug-free and lidocaine conditions, rather than between randomized treatment groups. The registry record does not report the order of the conditions, whether order was randomized, or how possible carryover was addressed. These omissions limit appraisal of whether condition-related differences might also reflect procedural or order effects.

The record does not report the number of participants included in the primary imaging analysis, the analysis population, or how missing or unusable data were handled. Enrollment is listed as 30, while the adverse-event risk denominator is 27; the registry does not explain that difference. Those figures should not be treated as interchangeable or used to infer the imaging analysis sample.

The registry lists 5 outcome measures and 2 analyses but does not describe their full mapping, any multiplicity adjustment, or a detailed statistical plan. It also does not report a sample-size justification for the actual design. The listed sample-size assumptions concern planning illustrations based on an observed effect and are not evidence of the trial’s original design rationale.

Finally, the study description specifies one visit and no long-term follow-up. The registry’s adverse-event counts therefore should be understood within the reported study context; they do not establish longer-term safety. The record does not provide further detail on event collection or follow-up completeness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Neural Correlates of Lidocaine Analgesia — NCT05501600.
• Registry record last updated 2024-12-24; status last verified 2024-12.
• Results first posted 2024-12-24.
• 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.

18. Record Summary

NCT05501600 is a completed phase I, single-group study titled “Neural Correlates of Lidocaine Analgesia.” Registry enrollment is 30. The study examined intravenous lidocaine in relation to pain processing and cognitive function using functional MRI, with peripheral nerve stimulation also listed as an intervention. The study description specifies one visit and no long-term follow-up.

The primary outcome is a Z-score contrast for brain activation to painful stimulation between drug-free and lidocaine conditions, listed for the right insula and measured over 4.5 minutes. The registry describes the score’s calculation and interpretation but does not report its numerical result or an uncertainty measure. Secondary outcomes concern pain intensity, memory performance, and motor response time.

The design is listed as single-group, with allocation not applicable and masking none. Serious adverse events, other adverse events, and deaths are each recorded as 0 in the listed Lidocaine group, with 27 participants at risk. The registry record does not report the analysis population, missing-data handling, or detailed multiplicity procedures.