Metaplasticity Experimental Design and Comparison of Motor Outcome Measure Sensitivity to Change: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Metaplasticity Experimental Design and Comparison of Motor Outcome Measure Sensitivity to Change (NCT03304262), a randomized na study. The primary outcome is Percent Change in MEP Amplitude.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, crossover study with an enrollment of 13 and a healthy-participant population. The registry lists three sequences: cathodal, then anodal, then sham; anodal, then sham, then cathodal; and sham, then cathodal, then anodal. Each condition combined tDCS with rTMS. In the sequence descriptions, the tDCS priming period lasted 10 minutes, and rTMS was described as 900 1Hz pulses at 0.85 of Resting Motor Threshold. The descriptions specify a 1 week washout between successive periods.

A crossover design means that the study is organized around participants receiving conditions in an assigned order, rather than each condition being confined to a separate parallel group. Randomizing the sequence can help prevent one order from being assigned systematically to particular participants. The record does not identify who was masked, explain the masking procedures, or report how order and period effects were handled in the statistical analysis.

The registry lists 13 participants for each condition’s outcome summary. These are condition-level entries in a crossover study and should not be added to infer a total number of distinct participants. The posted results do not include individual-level observations or paired comparisons, so it is not possible to assess how each participant’s outcome changed across the conditions.

The study status is completed. Its start date is 2017-07-18 and its primary completion date is 2018-02-28. The record identifies rTMS as a device intervention. It does not report a separate phase beyond NA, nor does it give further details of the protocol or statistical analysis plan.

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.

Before assignment: This was a crossover design, in which each participant came in three times and was randomly assigned to each intervention with a wash-out period in between.

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 Percent Change in MEP Amplitude, measured over assessed and reported throughout study completion pre- and post- intervention approximately 30 minutes.

The primary endpoint is percent change in MEP amplitude over the first dorsal interosseous (FDI) muscle of the right hand. MEP refers to a motor-evoked potential: a response measured after stimulation of the motor system. As a general concept, MEP amplitude can be used as a physiological measure of motor-cortex excitability. The registry’s stated objective is to assess changes in motor excitability after priming tDCS followed by rTMS.

Expressing the outcome as percent change focuses on the change from a pre-intervention measurement to a post-intervention measurement, rather than on the post-intervention amplitude alone. The record says measurements were assessed and reported throughout study completion pre- and post-intervention at approximately 30 minutes. It does not further define the calculation of percent change, the exact timing of the measurements within that interval, or how repeated measurements were summarized.

The endpoint is useful for addressing whether the experimental design captures a measurable physiological response and for comparing how motor outcome measures respond to the study conditions. The registry also lists Cortical Silent Period and Simple Reaction Time as secondary outcomes. No comparative estimates or tests are posted for the primary endpoint, so the endpoint summaries alone do not establish whether the conditions differ beyond their descriptive values.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the reported means describe?

The registry identifies the primary endpoint parameter as a mean and reports a value for each of the three stimulation conditions. A mean is a summary of the observed outcome values in a condition. Here, the outcome is percent change in MEP amplitude over the FDI muscle of the right hand. The posted means are 1.19 for cathodal tDCS plus rTMS, 1.06 for anodal tDCS plus rTMS, and 1.38 for sham tDCS plus rTMS.

These are descriptive summaries. They do not say whether the observed values differ more than would be expected from sampling variation, and they do not provide an adjusted estimate of a condition effect. The registry record has no analysis entries, and it does not report an inferential test for the primary outcome. The means should not be presented as evidence of statistical significance or as proof of no difference.

What does a full range tell the reader?

The outcome dispersion is reported as full range. The listed ranges are 0.43 to 5.65 for cathodal tDCS plus rTMS, 0.33 to 2.03 for anodal tDCS plus rTMS, and 0.19 to 2.82 for sham tDCS plus rTMS. A full range gives the minimum and maximum recorded values in the summarized condition. It can indicate how far apart the endpoints of the observed values are.

As a general statistical distinction, the full range is not a confidence interval. A confidence interval describes uncertainty around an estimated quantity under a specified method; the range simply reports the observed extremes. The range does not show the distribution of values between those extremes, and it is sensitive to extreme observations. Since the registry does not report standard deviations, standard errors, confidence intervals, or participant-level data, these summaries cannot be used to reconstruct a reliable uncertainty interval for a condition contrast.

Why does crossover structure matter?

In a crossover design, condition order is assigned and outcomes can be observed under multiple conditions for the same participant. The registry lists three randomized sequences and describes a 1 week washout between successive conditions. This design can make within-participant comparisons informative because each participant’s outcomes may be related across periods. As a general principle, an analysis that accounts for this pairing can differ from an analysis that treats all condition observations as independent.

The posted condition summaries do not include the pairing information. They also do not report an analysis accounting for sequence, period, or carryover. The record does not state whether or how these issues were assessed. A reader cannot derive a paired treatment contrast from the means and ranges alone because the association between each participant’s measurements across conditions is not reported.

How should the sample-size illustrations be read?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such calculations are prospective planning exercises: they show the number of participants per arm that would be associated with particular assumptions in a hypothetical design. They are not observed trial results and should not be described as observed power.

These illustrations do not establish the sample-size rationale used for this crossover study. The registry record does not report the trial’s own sample-size justification or a statistical plan explaining the selected assumptions. Nor do two-arm planning calculations automatically represent the analysis needed for a randomized crossover study with three conditions. The record’s planning assumptions should therefore be kept separate from the trial’s actual enrollment and from any claims about the precision of its posted outcomes.

What cannot be inferred from the posted summaries?

The condition-level means and ranges do not supply a test statistic, p-value, confidence interval, or a model-based effect estimate. They do not identify whether any contrast was prespecified or adjusted for other factors. The record also does not give a definition of the percent-change calculation beyond the endpoint description. As a general principle, inferential conclusions depend on the outcome definition, design, analysis method, and uncertainty estimate—not solely on the ordering of descriptive means.

The registry lists Cortical Silent Period and Simple Reaction Time as secondary outcomes, but no comparative results for them are included in the record. No result should be inferred from the fact that they were named as outcomes. Likewise, the absence of a posted test does not imply that a test was performed and was nonsignificant. The appropriate reading is that descriptive primary-outcome values are reported, while the statistical comparisons and their uncertainty are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, Percent Change in MEP Amplitude, and two secondary outcomes: Cortical Silent Period and Simple Reaction Time. It does not report a multiplicity strategy, such as how statistical error across multiple outcomes or contrasts would be controlled. Because no inferential analyses are posted, the record also does not show whether any adjustment was applied. The number and definition of planned comparisons are not reported in the registry record.

Missing-data handling is not reported in the registry record. The posted condition summaries each list 13 participants, but the record does not explain whether all randomized participants contributed to every measurement, how missing measurements would be handled, or whether any observations were excluded. The enrollment figure and the condition-level summary counts should not be treated as proof that every planned measure was complete.

The analysis populations are not reported in the registry record. There is no stated intention-to-treat, per-protocol, or other analysis-set definition, and no account of protocol deviations or withdrawals. The registry does not say whether the analyses were based on all participants assigned to a sequence or only those with particular measurements available.

These omissions limit interpretation of both the outcome summaries and the scope of any intended comparisons. They do not establish that data were missing, that analyses were adjusted, or that a particular analysis population was used. Those details would be needed to evaluate how complete the results are and how the multiplicity of outcomes and conditions was addressed.

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 registry reports serious adverse event counts separately for cathodal tDCS plus rTMS, anodal tDCS plus rTMS, and sham tDCS plus rTMS. For each condition, 13 participants are listed as at risk and 0 as affected by a serious adverse event. The record also lists 13 at risk and 0 affected by other adverse events for each condition, and deaths are reported as 0 in each condition.

These are the reported counts, not estimates of the probability of an adverse event. The record does not provide additional event details or serious adverse event terms. A count of 0 means that no events of that category are reported for the corresponding condition in this registry entry; it should not be expanded into a claim about risks outside the recorded study or about unreported events.

Because the study used a crossover design, condition-level at-risk entries should not be added to infer a number of distinct participants. The registry does not explain in this entry how safety follow-up was handled across periods. The figures are best read as condition-specific registry counts, with the scope of ascertainment and any further safety analysis not reported in the registry record.

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

The registry record documents a randomized, double-masked crossover study in healthy participants that examined priming tDCS followed by rTMS. It gives condition-specific summaries for percent change in MEP amplitude and identifies the study’s broader objective as validating a metaplasticity experimental design and comparing the sensitivity to change of motor outcome measures. This establishes what was studied and what descriptive primary-outcome results were posted.

The results do not establish that cathodal, anodal, or sham priming produced a statistically distinguishable change. The condition means are descriptive, and the registry does not report a test or an uncertainty interval for a comparison. The full ranges describe the observed endpoints, not uncertainty around the means. No conclusion of equivalence, benefit, or lack of effect follows from the summaries alone.

The record also does not establish that the experimental methodology was validated, because the validation objective is not accompanied by a reported inferential analysis. It lists two secondary outcomes, but no comparisons for those outcomes are posted. The registry does not report whether multiplicity, missing measurements, period effects, sequence effects, or carryover were addressed in analysis.

These limits are about what can be concluded from the registry record, not a claim that an analysis or additional information does not exist elsewhere. The posted entry supports a careful description of the design, endpoint, condition-level values, and safety counts. Stronger claims about comparative effects or measurement sensitivity would require analyses and methodological details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines three conditions in a randomized crossover design. In such a design, the order in which participants receive conditions and the relationship between repeated measurements can be important to interpretation. A condition-level mean alone does not preserve the paired information needed to understand how outcomes compare within participants. The registry’s sequences and washout descriptions make the design structure clear, while the lack of posted comparative analyses leaves its inferential implications unresolved.

The endpoint also illustrates the distinction between describing a physiological outcome and estimating a comparative effect. Percent change in MEP amplitude is summarized by a mean and full range for each condition. Those summaries communicate the recorded values, but they do not quantify uncertainty around differences between conditions. In particular, a full range should not be mistaken for a confidence interval or used as a substitute for a paired analysis.

The registry names both the validation of an experimental design and the comparison of motor outcome measure sensitivity to change as objectives. Those aims raise questions about how sensitivity is defined, how outcomes are compared, and how repeated observations are modeled. The record does not report the statistical plan or analyses that would answer those questions. This makes the study useful as an example of why design descriptions and descriptive outcome summaries need to be distinguished from inferential evidence.

For clinical researchers and biostatisticians, the key lesson is interpretive restraint: the reported values can be described exactly, but they do not support a comparative conclusion without the relevant analysis and uncertainty estimates.

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 registry provides limited information for evaluating the primary outcome beyond its name, unit, timing description, and condition-level summaries. It does not define the exact percent-change calculation or provide participant-level measurements. The reported dispersion is a full range, and no standard deviation, standard error, or confidence interval is reported. As a result, the precision of the means and of any contrast cannot be evaluated from the posted summaries.

The crossover design makes within-participant information particularly relevant, yet paired contrasts are not reported. The registry also does not state how sequence, period, or carryover effects were considered. The condition descriptions list washout periods, but the record does not report evidence about whether those periods were sufficient for the outcomes or whether residual effects were assessed. No assumptions about these matters should be made from the design description alone.

The registry lists 13 participants in each condition summary, but it does not explain missing-data handling, exclusions, withdrawals, or analysis-population definitions. The recorded enrollment and per-condition entries do not establish completeness across all outcomes or periods. The registry also does not report a multiplicity plan for the primary and secondary outcomes or for comparisons among the conditions.

Finally, the study population is described as healthy, and the record does not provide further participant characteristics in the registry entries. This limits how specifically the results can be interpreted beyond that population. The record’s stated objective and completed status do not substitute for the missing comparative estimates and analysis details needed to evaluate the outcomes statistically.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Metaplasticity Experimental Design and Comparison of Motor Outcome Measure Sensitivity to Change — NCT03304262.
• Registry record last updated 2023-08-25; status last verified 2023-08.
• Results first posted 2023-08-25.
• 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

This completed randomized, double-masked crossover study enrolled 13 healthy participants. Its objective was to validate a metaplasticity experimental design by assessing motor-excitability change after priming tDCS followed by rTMS. Three condition sequences were listed, with 1 week washout periods described between successive conditions.

The primary outcome was percent change in MEP amplitude over the FDI muscle of the right hand, assessed pre- and post-intervention at approximately 30 minutes. The registry reports condition means and full ranges for cathodal tDCS plus rTMS, anodal tDCS plus rTMS, and sham tDCS plus rTMS. It also lists Cortical Silent Period and Simple Reaction Time as secondary outcomes.

No inferential analyses, multiplicity approach, missing-data method, or analysis-population definition is reported in the registry record. Serious adverse events, other adverse events, and deaths are listed as 0 for each condition. The posted outcome values are descriptive and do not establish comparative effects.