Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia (NCT03860597), a randomized phase 4 study. The primary outcome is Prepulse Inhibition (PPI).

2. Clinical Question

The study summary frames a broader scientific aim: to examine whether neurophysiological measures of memantine-enhanced early auditory information processing in schizophrenia mediate gains in auditory processing fidelity and auditory learning. The registry's designated primary outcome is PPI, measured at 7 and 14 days post baseline. That endpoint is a specific physiological measure; it should not be treated as a direct measure of every process named in the broader aim.

The registry identifies a randomized, double-masked crossover study with an enrollment of 42. Its record does not provide a complete account of eligibility, the distribution of participants across diagnostic groups, or the planned estimand. Those details are not reported in the registry record, so the exact population and intended form of the memantine-versus-placebo comparison remain partly unspecified.

3. Trial Design

The registry identifies this as a phase 4, randomized, double-masked crossover study sponsored by the University of California, San Diego. Enrollment was 42. The record lists the study as completed, with a start date of 2018-04-01 and primary completion date of 2021-03-31. These administrative details describe the study record; they do not indicate what the outcome results were.

The primary outcome description specifies baseline testing on day 1, with data collected but no intervention given. Participants then received one intervention on day 7 post baseline and the other on day 14 post baseline. The two interventions were active memantine, stated as MEM 20 mg po, and placebo. The order was balanced, with some participants assigned placebo first and others memantine first. This arrangement means that each participant could contribute measurements under both intervention conditions, rather than being assigned to only one intervention condition.

In general, a crossover design uses within-participant comparisons. Such a design can account for stable differences between participants because each person is observed under both conditions. It also requires attention to the order and timing of treatment periods: a period effect, lingering effects from the first intervention, or changes over time could affect measurements. These are general design considerations, not claims about what occurred in this study. The registry record does not report a washout interval, a carryover assessment, or the statistical handling of period and sequence effects.

The adverse-event record divides participants into four sequence groups: participants with schizophrenia assigned to each order and healthy participants assigned to each order. The primary outcome description does not give corresponding group sizes or explain how all diagnostic groups were represented in the primary analysis. That information is not reported in the registry record. The record also does not describe masking procedures in detail, the randomization method, or a protocol for deviations from assigned sequence.

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.

6. Primary Endpoint

The registry lists the primary outcome as Prepulse Inhibition (PPI), measured over 7 and 14 days post baseline.

The primary endpoint is prepulse inhibition of the startle reflex, abbreviated PPI, measured as a percentage of inhibition. The record describes startle magnitude as assessed by electromyography of the orbicularis oculi. A pulse is a 40 ms, 118 dB(A) noise burst. On prepulse-plus-pulse trials, that pulse is preceded by a weak 20 ms burst set 16 dB over background, with the interval described as 10-120 msec. The percentage metric is calculated from the relative startle magnitude on prepulse-plus-pulse trials compared with pulse-alone trials.

PPI is used as a measure of sensorimotor gating: the reduction in response to a startling stimulus when it is preceded by a weaker stimulus. In general, a physiological measure can provide a way to quantify a response under specified testing conditions. The registry notes that the maximum possible inhibition is 100%, while there is no maximum negative value. It also cautions that higher or lower PPI does not have a clear universal advantage or disadvantage, although schizophrenia patients are described as having lower values on average than matched healthy subjects.

The endpoint is recorded as a continuous measure, summarized using a mean and standard error, at 7 and 14 days post baseline. The registry does not report the numerical outcome values or an intervention comparison. Consequently, the endpoint definition explains what was measured but does not establish the direction, magnitude, or precision of a memantine-placebo difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods explain how measured observations are converted into estimates and how uncertainty is assessed. The registry names a continuous primary outcome summarized by a mean and standard error. It does not identify a statistical test, model, adjustment set, or decision rule for the primary comparison. Any explanation of possible methods must therefore be read as general context, not as a description of the analysis actually used in this trial.

What does a mean describe?

In general, a mean represents the average of observed values in a defined group or condition. For a continuous measure such as PPI, it provides a central summary on the recorded percentage scale. A mean alone does not show how observations vary across participants, whether the distribution is skewed, or whether a few unusual values influence the average. Those features require additional summaries or the underlying observations. The registry identifies the measure as a mean but does not post the PPI means.

What does a standard error describe?

In general, a standard error describes the sampling uncertainty of an estimated quantity, such as a mean. It is not the same as the spread of individual participant values. A standard error can help characterize how precisely a mean has been estimated, but it cannot be interpreted without knowing the estimate, the sample contributing to it, and the analysis structure. Although the registry specifies standard error as the dispersion measure, no numerical standard errors for PPI are reported in the registry record.

Why does crossover structure matter?

In general, a crossover study observes each participant under more than one intervention condition. A comparison can then use the within-participant change or contrast, which often removes stable between-person differences from the treatment comparison. This does not automatically solve every design problem. Measurement occasions may differ over time, participants may respond differently in later periods, and effects of an earlier intervention may persist. A suitable analysis may need to account for treatment, period, and sequence, depending on the design and the intended estimand. These are general considerations only. The registry does not report which model, if any, was used or whether carryover or period effects were assessed.

Randomization assigns intervention order according to a chance-based process. In general, randomizing order can help prevent systematic differences in participant characteristics between sequence groups. Double masking is intended to limit knowledge of assigned intervention, which may reduce some sources of bias. The registry labels the trial randomized and double-masked but does not report the specific allocation process, masking procedures, or whether masking was assessed. No more detailed operational conclusion can be drawn from those labels alone.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the analysis, and communicates uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, while the interval's location relative to a relevant null value helps contextualize the estimated contrast. The registry record does not report a confidence interval for PPI or any other primary-outcome estimate. It therefore gives no basis for judging the precision of an intervention contrast.

A p-value, in general, describes how surprising data at least as incompatible with a specified null hypothesis would be under that hypothesis and the statistical model. It does not measure the probability that the null hypothesis is true, nor does it convey the size or practical importance of an effect. No primary-outcome p-value is reported. The fact that the registry lists zero analyses means no analysis entries are posted in the record; it does not establish what analyses may or may not have been conducted outside that registry entry.

What can be inferred from the design labels?

The labels continuous, mean, and standard error indicate the type of outcome summary selected for the record. They do not reveal how repeated observations were modeled, whether baseline PPI was used as a covariate, how within-person correlation was handled, or whether the analysis followed the randomized sequence. These methodological details are not reported in the registry record. An appropriate analysis depends on the question and the data structure; the design label alone cannot identify one.

The record also does not report a sample-size justification, target power, or a prespecified clinically meaningful difference. General sample-size calculations depend on an assumed effect, variability, allocation, significance level, and analysis design. Without a documented rationale, the enrollment of 42 cannot be interpreted as evidence that the study was adequately powered for a particular PPI contrast. Any planning illustration based on an observed effect would be retrospective and would not describe the trial's original design or observed power.

In short, general statistical concepts can clarify how means, standard errors, and crossover comparisons are commonly interpreted, but they cannot fill the gaps in this registry entry. The primary analysis method and its results are not reported in the registry record. The numerical effect and uncertainty remain unknown from the posted information.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is recorded at 7 and 14 days post baseline, and the registry notes that the outcome has several categories or time points and is not reduced to one comparison. This creates an interpretive issue: multiple outcomes, categories, time points, or contrasts can lead to more than one opportunity to identify a result that appears unusual. In general, a prespecified approach to multiplicity clarifies which comparisons are primary and whether any adjustment or hierarchy is used. The registry record does not report such an approach.

The record lists three outcome measures, but it does not give a complete statistical analysis plan, identify a single primary contrast across the time points, or report multiplicity adjustments. Those details are not reported in the registry record. No conclusion can be drawn about whether multiplicity was addressed outside the registry entry.

Missing-data information is also limited. The enrollment is 42, but the record does not report the number with PPI observations at each occasion, the number completing both intervention periods, reasons for missing measurements, or any imputation or sensitivity analysis. In general, missingness can affect the target population represented by an analysis and can bias estimates if the chance of missing data is related to outcomes or participant characteristics. The registry does not provide enough information to evaluate those possibilities.

The analysis population is not specified for the primary outcome. The record does not say whether the primary analysis included all randomized participants, only those who completed both periods, or another defined group. The handling of protocol deviations and incomplete crossover sequences is likewise not reported in the registry record. These omissions limit assessment of how representative the analyzed participants were of the randomized study population and how robust any estimated contrast might be.

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 adverse-event record separates participants by diagnostic group and intervention order. In each of the four listed groups, the number at risk for serious adverse events is recorded as 11, 11, 10, and 10, respectively; the corresponding serious adverse event counts are all 0. The number at risk for other adverse events is also recorded as 11, 11, 10, and 10, with counts of 0 in every group. Deaths are recorded as 0 in each group.

These figures are event counts in the registry's sequence groups. Because this is a crossover study, each group title describes an order in which placebo and memantine were received, not a simple parallel comparison of participants exposed only to one intervention. The posted counts do not specify event timing by intervention period, establish attribution to either intervention, or provide a separate exposure-adjusted comparison. The registry does not report those details.

A recorded count of zero means no events were entered in that category for the corresponding group in this record. It does not establish that an intervention is free of risk or that every possible adverse event was captured. The registry does not list serious adverse-event terms, and the record does not provide a broader narrative of safety monitoring or follow-up. These counts should therefore be read narrowly as the posted event figures, not as a complete comparative safety analysis.

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

The record supports a clear description of the study's intended measurement and treatment sequence. It identifies a randomized, double-masked crossover trial of memantine and placebo, with PPI of the startle reflex as the primary endpoint. Baseline testing occurred on day 1, and the two interventions were scheduled on day 7 and day 14 post baseline in balanced order. The endpoint is expressed as percentage inhibition and summarized as a mean with standard error.

The record does not report the primary outcome results. It contains no PPI means, intervention difference, confidence interval, p-value, or analysis details. As a result, it cannot show how PPI values differed between the memantine and placebo conditions, how precise a difference might be, or whether a statistical test supported a claim. The study's completion status and scientific aims do not substitute for those missing results.

Likewise, the trial record does not establish whether PPI changes mediated gains in auditory processing fidelity or auditory learning. The brief summary describes that as an aim, but the posted primary outcome is PPI, and no mediation estimate or results for the broader claim are reported. The endpoint definition alone cannot answer a mechanistic question.

The adverse-event entries report zero serious and other adverse events in each listed sequence group and zero deaths. Those figures are limited registry counts. They do not establish the absence of risk, provide event attribution by intervention, or replace a full comparative safety analysis.

In general, a clinical trial's meaning depends on the correspondence between its question, design, outcome definition, analysis, and reported uncertainty. Here, the question and broad design are described, but the outcome estimates and analysis are not. The scientifically appropriate reading is therefore descriptive: the record documents a crossover study and its intended physiological measure, while leaving the treatment contrast and its precision undetermined in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure. Instead of assigning each participant to only memantine or only placebo, the described schedule gives each participant both interventions in a balanced order. In general, that design can make within-person contrasts informative because stable characteristics are shared across the participant's observations. It also makes analysis choices important: the timing of observations, order of interventions, and potential persistence of effects can influence interpretation.

The endpoint is a physiological measure with a specific operational definition. PPI is derived from relative startle magnitude under prepulse-plus-pulse and pulse-alone conditions, and is reported as percentage inhibition. Such precise measurement definitions matter because they clarify what a statistical estimate would represent. They also prevent a percentage score from being mistaken for a direct measure of every broader cognitive or auditory process named in the study summary.

The registry record also illustrates the difference between trial registration details and a complete results report. It records the design, timing, outcome definition, enrollment, and adverse-event counts, but it does not post primary-outcome estimates or analysis methods. Without those, a reader cannot evaluate the magnitude or precision of the intervention comparison. Statistical significance, even if reported elsewhere, would not by itself convey effect size or uncertainty; neither is available in this registry entry.

Finally, the study's stated aim reaches beyond a single physiological endpoint, referring to early auditory information processing, auditory processing fidelity, and auditory learning. Connecting a physiological measure to those broader processes requires relevant outcome data and an explicit analysis. The registry record does not report such results. The central statistical lesson is that design and measurement can be described in detail while the evidence needed to quantify an intervention contrast remains absent from the record.

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 this study from the registry record is the absence of posted PPI results. No numerical summaries or intervention contrast are reported, so neither the estimated direction nor the magnitude and precision of the primary comparison can be assessed. The record also lists no analysis entries. This prevents evaluation of the actual inferential method and its assumptions.

Important crossover details are not described. The record gives the intervention order and test days but does not report a washout interval, how potential carryover was considered, or how period and sequence were handled analytically. These are general concerns for crossover interpretation, not evidence that a particular bias occurred. The method used to account for repeated measurements is not reported in the registry record.

Details about the primary analysis population and missing observations are also absent. Enrollment does not establish how many participants contributed complete measurements under both conditions. The registry does not report outcome-specific denominators, reasons for missing data, exclusions, or sensitivity analyses. This makes it impossible to assess whether incomplete data could affect the interpretation.

The record does not describe the randomization procedure, masking implementation, sample-size justification, or a prespecified analysis plan. It also does not explain the relationship between all listed condition labels and the diagnostic groups used in the adverse-event record. The outcome is recorded at multiple time points, but no primary comparison or multiplicity strategy is specified. These gaps constrain assessment of internal validity, precision, and generalizability without demonstrating that any particular problem occurred in the conduct of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia — NCT03860597.
• Registry record last updated 2022-12-21; status last verified 2022-12.
• Results first posted 2022-12-21.
• 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

NCT03860597 is a completed phase 4 randomized, double-masked crossover study sponsored by the University of California, San Diego, with enrollment of 42. The record describes memantine and placebo given in balanced order after baseline testing, with interventions scheduled for day 7 and day 14 post baseline.

The primary outcome is prepulse inhibition of the startle reflex, expressed as percentage inhibition and summarized by a mean and standard error. The registry does not report primary-outcome estimates, a treatment comparison, or the statistical analysis method. It lists zero serious adverse events, zero other adverse events, and zero deaths in each of four sequence groups. These are the registry's posted counts and do not constitute a complete comparative safety analysis.