BOTOX Effects on Seizure Severity and Susceptibility: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BOTOX Effects on Seizure Severity and Susceptibility (NCT05605756), a na phase 4 study. The primary outcome is Change in Net Cortical Excitability Metrics.

2. Clinical Question

In practical statistical terms, the intended question was whether cortical excitability measures changed across the planned measurement periods in people with drug-resistant focal seizure receiving the listed intervention. The description names resting motor threshold (rMT), cortical silent period (CSP), long-interval intracortical inhibition (LICI), and TMS-EEG excitability metrics. It says metric values would be averaged across trials within each time block and compared using a repeated-measures approach.

The record does not establish that these measurements were collected. It explicitly states that none of the patients who consented reached baseline, and it lists no analyses. Thus, the clinical question remains an intended research question rather than one answered by results in the registry record. No estimate of change, uncertainty interval, or statistical test result is reported.

3. Trial Design

The registry classifies this as a Phase 4, single-group study. Allocation is recorded as NA, and masking as none. These entries describe a design without a randomized allocation or a masked comparison. The registry lists an enrollment of 3 and a status of terminated. It gives a start date of 2023-03-01 and a primary completion date of 2024-12-01; the reason for termination and the timing of termination are not reported in the registry record.

The listed intervention is OnabotulinumtoxinA 145 UNT [Botox]. The record does not report a separate control arm. Its arm description names “Botox therapy effects on seizure,” but does not provide further details about treatment delivery, follow-up procedures, or adherence. The record does not say whether the intervention was administered to any participant. In particular, the statement that no consented patients reached baseline means that the planned baseline assessment was not reached by those who consented; it does not establish what happened at every later stage.

The primary outcome timeframe is 150 days. Its measurement description specifies baseline and follow-up blocks at 3 weeks and 8 weeks after BOTOX injections, while the outcome title refers to change in cortical excitability metrics. The registry does not explain how the 150-day timeframe relates to the measurement blocks. That relationship, including whether the timeframe refers to a broader follow-up period, is not reported in the registry record.

The brief summary explains the rationale as testing BOTOX for seizure frequency and severity because epilepsy and migraine have common features and are often treated with common drugs. This is the stated rationale, not a finding from the study. No protocol details beyond the registry descriptions are reported, including the planned sample-size justification, detailed eligibility criteria, or operational procedures for the intervention and assessments.

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

Analysis population for the primary outcome, as defined in the registry: none of the patients that consented reached the baseline timepoint for the trial

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: We screened hundreds of patients. Recruited 3 but never reached the treatment phase

6. Primary Endpoint

The registry lists the primary outcome as Change in Net Cortical Excitability Metrics, measured over 150 days.

The primary outcome is titled “Change in Net Cortical Excitability Metrics,” with the unit recorded as participants and the parameter described as a count of participants. Its measurement description, however, focuses on values of TMS and TMS-EEG metrics. It names rMT, CSP, LICI, and TMS-EEG excitability metrics, to be averaged over at least 20 trials per subject per time block. The stated blocks are baseline, 3 weeks, and 8 weeks after BOTOX injections.

The description says that mean values for each metric would then be compared using one-way repeated measures ANOVA. In general, repeated measurements can help assess within-participant change over time, because measurements from the same person are related rather than independent. Cortical excitability metrics are the planned physiological measures; the registry does not explain a clinical threshold for interpreting a change in these metrics or how any change would relate to seizure severity.

There is a notable difference between the outcome’s recorded count-based unit and the description of averaging and comparing metric values. The record does not explain whether a count of participants was intended to represent a threshold-defined response, or how that count would be derived from the continuous measurements. No such threshold or response definition is reported. More importantly, no patients who consented reached the baseline timepoint, and no analysis results are listed. Therefore, the registry does not provide observed endpoint values or a comparison of changes across the planned time blocks.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a repeated-measures analysis aim to assess?

The outcome description proposes comparing mean values of each excitability metric across measurement blocks with one-way repeated measures ANOVA. In general, this method is used when the same participant is measured under multiple conditions or at multiple times. It accounts for the fact that measurements from one participant tend to be related. Treating those measurements as if they came from unrelated people can misrepresent the amount of information in the data and distort uncertainty.

For this study, the description names baseline, 3 weeks, and 8 weeks after BOTOX injections as the measurement blocks. It also says each metric would be averaged over at least 20 trials per subject per time block before the time-block comparison. Repeated trials can support a more stable summary for a participant, but the participant remains the unit that links measurements over time. The registry does not report the actual measurements, participant-level summaries, model results, or checks of model assumptions.

What assumptions matter for this method?

General statistical context: repeated-measures ANOVA relies on assumptions about the distribution and structure of the measurements and the relationship among repeated observations. The appropriateness of the method depends on the observed data and study design. If assumptions are poorly supported, estimates and tests may not have their intended interpretation. No diagnostic checks, transformations, alternative models, or decision rules are reported in the registry record. With no baseline reached and no analyses listed, it is not possible to assess whether the planned method was applied or whether its assumptions were considered.

The registry describes the endpoint as a count of participants, but describes averaging metric values and comparing their means. General statistical context: a count of participants is a different kind of outcome from a continuous measurement such as a metric mean. A count-based endpoint would usually need a definition of which participants qualify for the count, such as a specified response criterion. No such criterion appears in the record. The registry does not explain this difference between the recorded outcome type and the measurement description, so the precise intended analysis target is unclear.

What does a confidence interval or p-value contribute?

General statistical context: an effect estimate describes the direction and magnitude of a contrast or change, while a confidence interval communicates the precision of that estimate under the analysis assumptions. A p-value evaluates how compatible the data are with a specified null model; it is not a measure of effect size or clinical importance. These quantities require analyzed data and a defined statistical model. The registry reports no effect estimate, confidence interval, or p-value, so none can be interpreted for the primary outcome.

A statistically detectable difference would not, by itself, establish that a change is clinically important. Conversely, a non-significant result would not prove the absence of a meaningful effect, particularly when data are sparse or estimates imprecise. General statistical context: interpretation should consider the size of the estimated change, its uncertainty, the endpoint’s clinical meaning, and the design. In this record, those assessments cannot be made because no outcome analysis is reported.

How should the planning illustration be read?

The registry describes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes total events for time-to-event planning from participants per arm for other planning calculations. These are planning conventions, not study results. The record’s registered design is single-group, not a two-arm comparison, and the registry reports zero analyses. Thus the assumptions described for the illustration should not be taken as evidence that the study used those design features or that it had a particular probability of detecting an effect.

General statistical context: power is a property of a planned design under assumed effect, variability, analysis, and significance criteria. It is not a measure of whether a completed study happened to find a result. Planning calculations based on an observed effect can be especially difficult to interpret when the record reports no analysis from which an observed effect could be established. Any planning values should therefore be understood as illustrations, not observed power and not a retrospective explanation of the study’s outcome.

What can be concluded about the analysis?

The registry states that no patients who consented reached baseline and records zero analyses. It does not report an analysis population, a missing-data method, an adjustment strategy, or a multiplicity plan. It also does not report a protocol-level statistical analysis plan or explain whether any analyses were planned outside the registry record. These absences limit what can be said about the intended inferential procedure. They do not justify assuming that unreported methods were used.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome titled “Change in Net Cortical Excitability Metrics,” describes several TMS and TMS-EEG metrics, and names “Change in Quality-of-life Metrics” as a secondary outcome. It does not report how testing across the multiple excitability metrics would be handled, whether a single metric was designated as the principal test, or whether any adjustment for multiple comparisons was planned. A multiplicity strategy is not reported in the registry record.

General statistical context: when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate plan. Approaches to multiplicity depend on the scientific question and analysis plan. The record does not give enough information to determine whether multiplicity was considered or how it would have been addressed. Since no analyses are listed, there are no reported tests to assess for multiplicity.

The registry says none of the patients who consented reached baseline. It does not provide a detailed account of missing measurements, reasons for non-completion, or any imputation or other missing-data method. The reason baseline was not reached is not reported in the registry record. There is therefore no basis for evaluating whether missingness was related to participant characteristics, treatment, or outcome, or for judging a method for handling missing values.

An analysis population is not reported. The record does not specify whether the intended analysis would include all enrolled participants, only those receiving the intervention, or only participants with measurements at specified timepoints. Nor does it describe any rule for handling incomplete repeated measurements. The stated enrollment and the statement that baseline was not reached should not be used to infer an analyzed population, because the record lists zero analyses and gives no participant-level disposition.

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

The registry record documents a planned investigation of BOTOX and seizure-related questions, with cortical excitability metrics as the primary outcome and quality-of-life metrics as a secondary outcome. It also documents that the study was terminated and that none of the patients who consented reached baseline. No analyses are listed. These registry entries mean the record does not provide an outcome estimate for the primary or secondary question.

This does not show that cortical excitability changed, and it does not show that it remained unchanged. It does not establish a reduction or increase in seizure frequency or severity. The brief summary states the study’s purpose, but a purpose is not a result. No conclusion about benefit, lack of benefit, or harm can be drawn from the absence of reported analyses.

The lack of a comparator is another important boundary. Even if within-group measurements had been reported, a single-group design would not provide a randomized comparison with a control group. Changes observed over time could have more than one explanation. In this record, there are no baseline measurements to interpret, so that broader limitation is secondary to the absence of analyzed outcome data.

The adverse-event entries report zero at risk and zero events in the listed group. Because the at-risk count is zero, those entries should not be interpreted as demonstrating an absence of adverse events among treated participants. The registry does not establish exposure or provide a monitored treated population for this purpose. Safety conclusions cannot be inferred from these counts.

General statistical context: a study’s ability to answer a question depends on whether relevant measurements were collected, how they were analyzed, and how precisely effects were estimated. A planned endpoint, a sample-size illustration, or a registry status cannot replace outcome data. The record is informative about the intended measurement strategy and its documented non-attainment of baseline, but it does not quantify an effect or its uncertainty.

12. Why This Trial Matters Statistically

Statistically, this record illustrates the distinction between a planned endpoint and an analyzable endpoint. The registry describes repeated cortical excitability measurements and a method for comparing them over time, but also states that no consented patients reached baseline. Without the baseline measurement, the planned change-from-baseline question cannot be answered from the record. The absence of analyses makes that limitation explicit.

The record also highlights why endpoint definitions need to align with the analysis. The title refers to change in cortical excitability metrics, and the description concerns averaged metric values; the recorded unit and parameter refer instead to participants and a count. That mismatch leaves uncertainty about whether the intended target was a continuous change in measurements or a count of participants meeting a response definition. The registry does not supply a response threshold or clarify the discrepancy.

A further statistical lesson concerns design alignment. The study is registered as single-group, yet the described planning illustration uses equal allocation between two arms. Planning calculations depend on the design and assumptions they represent. An illustration built around a different comparison should not be mistaken for a design justification or for evidence about the study’s achieved precision.

Finally, the record separates a scientific rationale from an empirical result. Its brief summary explains why the investigators chose to study BOTOX in relation to epilepsy, but the registry contains no analyzed outcome evidence to evaluate that rationale. Clear reporting of participant progression, measurement completion, analysis populations, endpoint definitions, and statistical methods is essential for interpreting what a terminated study can and cannot establish.

13. 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 most direct limitation is that none of the patients who consented reached the baseline timepoint for the trial. The primary outcome description depends on measurements at baseline and subsequent time blocks, so the record does not document the data needed for the stated change analysis. It also records zero analyses. The reason baseline was not reached and the reason for termination are not reported in the registry record.

The registry’s endpoint fields do not fully align: the title and measurement description concern changes in cortical excitability metrics, while the recorded unit and parameter describe a count of participants. No responder definition or threshold is reported. This makes the exact intended estimand—the quantity the analysis was intended to estimate—unclear from the record.

The study is single-group, with no randomized or masked comparison recorded. The registry does not report whether the listed intervention was administered, whether treatment exposure occurred, or how participants moved through the study. It also does not report detailed eligibility criteria, a missing-data strategy, an analysis population, multiplicity handling, or a statistical analysis plan. These omissions limit assessment of both the intended analysis and the reasons results are unavailable.

The primary outcome timeframe is listed as 150 days, while the measurement description names baseline, 3 weeks, and 8 weeks after injections. The record does not explain how these time references fit together. The listed adverse-event counts include zero participants at risk, so they do not provide an interpretable safety assessment of exposed participants. Finally, the planning illustration is described using a two-arm framework that differs from the registered single-group design; it cannot establish the study’s actual precision or power.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: BOTOX Effects on Seizure Severity and Susceptibility — NCT05605756.
• Registry record last updated 2026-06-29; status last verified 2026-02.
• Results first posted 2026-06-29.
• 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.

17. Record Summary

NCT05605756 is registered as a Phase 4, single-group study titled “BOTOX Effects on Seizure Severity and Susceptibility.” The listed condition is drug-resistant focal seizure, and the intervention is OnabotulinumtoxinA 145 UNT [Botox]. Allocation is recorded as NA, masking as none, enrollment as 3, and status as terminated. The registry lists a start date of 2023-03-01 and a primary completion date of 2024-12-01.

The primary outcome concerns change in net cortical excitability metrics, with planned TMS and TMS-EEG measurements and a repeated-measures ANOVA description. Quality-of-life metrics are listed as a secondary outcome. The record states that none of the patients who consented reached baseline and reports zero analyses. It does not report outcome estimates or explain the reason for termination. The adverse-event group has zero participants at risk and zero reported serious or other events; these entries do not establish that treated participants were monitored without events.