Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity (NCT02268461), a randomized na study. The primary outcome is Change From Baseline Contralesional Corticospinal Excitability.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, triple-masked crossover study of rTMS for post-stroke spasticity. It is marked completed, with enrollment of 4. The sponsor is the University of Minnesota. The recorded start is 2014-12 and the primary completion is 2016-10. The phase is listed as NA.

The registry describes two treatment sequences: “rTMS then Sham rTMS” and “Sham rTMS then Real rTMS.” This indicates that participants were assigned to sequences of conditions rather than being described only as belonging to separate parallel treatment groups. The exact allocation ratio, timing between conditions, and procedures for managing possible period or carryover effects are not reported in the registry record.

The intervention entries identify rTMS and sham rTMS as devices. The posted primary outcome summary uses the group labels “rTMS” and “Real rTMS,” each with n=4. Those labels and summaries do not establish how the crossover measurements were organized or whether values represent individual periods, sequences, or another analysis unit. That detail is not reported in the registry record.

Triple masking means the registry records masking at three levels, but it does not specify which people or roles were masked. The masking procedures are not reported in the registry record. The record contains no inferential analyses for the primary outcome, so the design description alone cannot establish an estimated treatment contrast.

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 Change From Baseline Contralesional Corticospinal Excitability, measured over From Day 1 to Day 5.

The primary endpoint is change from baseline in contralesional corticospinal excitability, measured in microVolts from Day 1 to Day 5. The registry describes the measurement as the average amplitude of 10 motor evoked potentials (MEPs) at baseline compared with the average of 10 MEPs at post-test. MEPs were measured using surface electromyography. The recorded change is the difference between those averages.

The registry specifies the direction of interpretation: a greater negative value indicates larger post-test MEPs and increased corticospinal excitability. This direction matters when interpreting the sign of a mean change; a negative value should not automatically be read as a decrease in excitability.

As a physiological measure, corticospinal excitability can characterize a response in the motor pathway. General statistical and clinical context: a physiological endpoint can help assess a proposed mechanism, but it is not itself a direct measure of daily function, disability, or the experience of spasticity. The registry lists change in Stroke Impact Scale as a secondary outcome. A clinically meaningful threshold for the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it records a measured quantity in microVolts, and the registry reports group means and standard deviations. General explanation: a mean describes the central value of observations on a numeric scale. A standard deviation describes how dispersed observations are around that mean. It does not, on its own, quantify the precision of a comparison or show whether a difference is statistically compatible with no effect.

What the crossover design changes

General explanation: in a crossover trial, participants receive conditions in a sequence, so measurements under different conditions may come from the same person. A treatment comparison can then use within-participant changes, which depend on the pairing between a participant’s measurements. That pairing is important because observations from one person are often related. Group means and standard deviations do not retain the pairing information.

The registry records a randomized, triple-masked crossover design and identifies the sequences as “rTMS then Sham rTMS” and “Sham rTMS then Real rTMS.” The posted outcome summaries do not explain how those sequence assignments correspond to the labels “rTMS” and “Real rTMS,” or whether the summaries refer to period-specific measurements. Participant-level paired data and the analysis method are not reported in the registry record. The registry also indicates that a two-arm comparison for this continuous endpoint was not estimable. It would therefore be inappropriate to reconstruct a crossover treatment contrast from the posted group summaries.

Means, spread, and precision

The reported means are 67.88 and -37.23 microVolts, with standard deviations of 384.9 and 542.1, respectively. General explanation: a confidence interval expresses uncertainty around an estimate using a range of values consistent with the data and the chosen method. Its width depends on factors including the amount of information and variability. The registry does not report a confidence interval for this endpoint. Without a valid estimated contrast and its uncertainty, the reported descriptive summaries do not establish the precision of a treatment comparison.

Likewise, a p-value would address how compatible the observed data are with a specified statistical model and null hypothesis. It would not describe the size or clinical importance of an effect. No p-value or inferential analysis is reported for this endpoint. The absence of an inferential result should not be replaced by an interpretation based only on which group mean is more negative.

Why variability matters

General explanation: over-dispersion means that observations vary more than a model assumes. If a method assumes less variability than is present, its uncertainty estimates can be too narrow and its inference too confident. In a small study, a few observations can strongly influence a mean and the estimate of spread. Here, the standard deviations summarize variability, but the record does not provide participant-level observations or enough detail to evaluate the distribution or the crossover pairing. No particular distributional problem or model failure can be inferred from the summaries alone.

Planning assumptions are not observed power

The registry’s planning assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such planning calculations are hypothetical illustrations, not evidence about the chance that this completed study detected an effect. They are not observed power and do not repair the lack of an estimable comparison. A numerical planning result is not reported in the registry record. The trial’s own sample-size justification is also not reported in the registry record.

What an appropriate analysis would need

General explanation: an analysis of crossover data generally needs to preserve the relationship between each participant’s measurements and consider how treatment sequence and period are represented. Depending on the design and available data, models may also need to account for other features specified in the analysis plan. This is general methodological context, not a description of the study’s actual analysis. The protocol, statistical analysis plan, handling of period effects, and method for addressing possible carryover are not reported in the registry record.

The record reports descriptive statistics and states that a two-arm comparison was not estimable. It does not report the participant-level data, fitted model, standard error for a contrast, confidence interval, or inferential test needed to assess a comparative result. The posted summaries should therefore be read as descriptive only.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("rTMS", "Real rTMS")
n   <- c(4, 4)
m   <- c(67.88, -37.23)
sp  <- c(384.91, 542.11)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  rTMS  4  67.880  384.910  -544.598  680.358
CARM  Real rTMS  4  -37.230  542.110  -899.848  825.388

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Change in Stroke Impact Scale and Change From Baseline Resting Motor Threshold as secondary outcomes, and reports 4 outcome measures. It does not report a multiplicity strategy, such as whether particular outcomes were designated as confirmatory or how inference across outcomes would be controlled. The number of analyses is listed as 0. Without an analysis plan or inferential results, it is not possible to determine whether multiple testing affected interpretation.

Missing-data handling is not reported in the registry record. The record does not describe whether any endpoint measurements were missing, how missing observations were handled, or whether sensitivity analyses were planned. The statement that values were missing or not estimable for a two-arm comparison identifies a limitation in the reported comparison; it does not establish why that comparison was unavailable or whether participant outcome measurements themselves were missing.

The analysis population is not reported in the registry record. It is not stated whether outcomes were analyzed according to randomized sequence, treatment received, completion of both periods, or another rule. The registry reports enrollment of 4 and n=4 for each posted primary outcome group summary, but those counts do not clarify the analysis population in a crossover design or establish that the same individuals contributed to both summaries.

These omissions matter because missingness, outcome selection, and analysis-population definitions can affect the interpretation of estimates. No assumptions about these matters can be inferred from the descriptive results.

12. 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.

For the rTMS group, the registry reports 4 participants at risk for serious adverse events and 0 affected. For the Sham group, it also reports 4 at risk and 0 affected. Deaths are reported as 0 in both groups. The record lists no serious adverse event terms.

The registry also reports other adverse events: 0 affected among 4 at risk for rTMS and 0 affected among 4 at risk for Sham. These are counts for the groups as labelled in the safety record. The study is described as a crossover, but the record does not explain how safety exposure across treatment periods was assigned or summarized.

General explanation: an observed count of zero means no affected participants were recorded in that group in the registry entry. It does not prove that an event cannot occur or precisely establish the frequency of uncommon events. With enrollment of 4, these counts provide limited information about safety. The adverse-event figures do not establish comparative safety, and they should not be interpreted as evidence that a treatment is safe or unsafe.

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

The posted results establish that the registry contains descriptive primary-endpoint summaries for groups labelled “rTMS” and “Real rTMS,” each with n=4. The reported means are 67.88 and -37.23 microVolts, respectively, and the standard deviations are 384.9 and 542.1. The endpoint description says that a greater negative value indicates larger post-test MEPs and increased corticospinal excitability. These registry entries describe the posted summaries, but they do not constitute an interpretable estimate of the difference between treatment conditions.

The study is recorded as randomized, triple-masked, and crossover. The registry indicates that a two-arm comparison for the continuous endpoint was not estimable. No inferential analysis or confidence interval is reported. Therefore, the posted results do not establish whether rTMS changed corticospinal excitability compared with sham. They also do not establish whether there was a change in spasticity, arm function, or quality of life.

General explanation: a physiological measure can help characterize a biological response, but that response is not automatically equivalent to a meaningful change in symptoms or daily function. The registry lists the Stroke Impact Scale as a secondary outcome, but the registry entries available for interpretation do not include its results. A clinical interpretation of that outcome is therefore not possible from this record.

The absence of an estimable comparison is not evidence that the conditions were equivalent. Nor does a difference between descriptive means prove that the conditions differed. A comparative conclusion requires an analysis suited to the crossover design and an estimate with appropriate uncertainty. Those are not reported in the registry record. The appropriate conclusion is limited: the record offers descriptive values and safety counts, but not a supported comparative treatment result.

14. Why This Trial Matters Statistically

This trial illustrates why design labels and outcome summaries need to be read together. A crossover study assigns treatment sequences, and its comparison can depend on the relationship between repeated measurements from the same participants. A set of group means and standard deviations cannot by itself show those within-person changes. In this record, that distinction is especially relevant because the registry identifies a crossover design but says a two-arm comparison for the continuous outcome was not estimable.

The record also highlights the difference between a physiological endpoint and a clinical outcome. Contralesional corticospinal excitability was assessed through MEP amplitude, while Stroke Impact Scale was listed as a secondary outcome. A measured physiological change can be informative about a proposed response, but it does not alone demonstrate a change in function or quality of life. Keeping the endpoint’s meaning separate from broader treatment aims helps prevent overinterpretation.

Enrollment of 4 makes the descriptive summaries difficult to generalize, and the lack of a comparative estimate leaves their precision unknown. The reported standard deviations describe spread, not the uncertainty of an effect estimate. No inferential analysis is reported. The record thus provides a useful example of why descriptive data, design information, and analysis details answer different questions.

Statistically, the central lesson is not a conclusion about treatment benefit. It is that the form of the reported data must match the study design before a treatment contrast can be interpreted. When that match and the necessary analysis details are absent, careful description is more informative than an unsupported numerical comparison.

15. 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.

Enrollment was 4, and the registry reports n=4 for each primary outcome group summary. This provides limited information about variability and makes the descriptive means sensitive to individual observations. The posted standard deviations are 384.9 and 542.1, but they do not supply the uncertainty of a treatment contrast.

The most direct limitation is that the registry states values were missing or not estimable for a two-arm comparison of the continuous endpoint. The reported means and standard deviations do not resolve that issue. The crossover sequence labels and the outcome group labels are not fully linked in the record, and participant-level paired outcomes are not reported. Consequently, the summaries cannot be interpreted as a valid comparative effect.

The record does not report the protocol or statistical analysis plan, sample-size justification, analysis population, missing-data approach, inferential model, confidence interval, or p-value. It also does not report how period or possible carryover effects were handled. These omissions limit assessment of the analysis and the robustness of any potential treatment comparison.

The primary endpoint measures corticospinal excitability, not spasticity or upper limb function directly. Although the registry lists a functional secondary outcome, its result is not available among the registry entries reported for interpretation. A clinically meaningful threshold for the primary endpoint is also not reported in the registry record. The safety counts are based on small groups and do not establish the frequency of uncommon events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity — NCT02268461.
• Registry record last updated 2025-01-27; status last verified 2025-01.
• Results first posted 2025-01-27.
• 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.

19. Record Summary

NCT02268461 is a completed randomized, triple-masked crossover study sponsored by the University of Minnesota, with enrollment of 4. The registry records a start of 2014-12 and primary completion of 2016-10. It examined rTMS and sham rTMS in relation to post-stroke upper limb spasticity.

The primary endpoint was change in contralesional corticospinal excitability from Day 1 to Day 5, measured in microVolts using MEPs recorded with surface electromyography. The posted group summaries are mean 67.88 with standard deviation 384.9 for “rTMS,” and mean -37.23 with standard deviation 542.1 for “Real rTMS,” with n=4 in each group. The registry states that a two-arm comparison was not estimable and lists 0 analyses.

Serious adverse events and deaths are reported as 0 in each safety group. The record does not provide a supported comparative estimate for the primary endpoint.