Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy (NCT05126693), a non-randomized na study. The primary outcome is Change in Normalized Muscle Volume of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus.

2. Clinical Question

3. Trial Design

The registry describes a completed, parallel-group study with non-randomized allocation and no masking. It enrolled 61 participants and lists spastic cerebral palsy as the condition. The intervention was an integrated botulinum toxin treatment approach; the comparison group continued usual care. Because allocation was not randomized, the groups should not be treated as automatically comparable at baseline. The registry itself flags the arms as not being a like-for-like control comparison.

The intervention group was scheduled to receive injections in the medial gastrocnemius and/or semitendinosus. The study description says the integrated approach combines injections with serial casting and intensive physical therapy. The named intervention also describes a post-injection intensive physical therapy period guided by individualized treatment goals. The control group continued its usual routine, described as physiotherapy and orthotic management during 8-10 weeks. The primary outcome follow-up was between baseline and 8-10 weeks after injections for the intervention group, and between baseline and 8-10 weeks later for controls.

The registry lists a start date of 2020-08-03, a primary completion date of 2022-05-10, and a completed status. It does not report the method used to allocate children to groups, criteria for eligibility, baseline group summaries, or details of adherence to treatment. Although the brief description refers to 30 children in each group, the registry's enrollment figure is 61; the record does not explain the relationship between the planned group counts and the final enrollment figure. Actual group sizes for the main comparison are not reported in the registry record.

The record names 17 outcome measures, including muscle and tendon characteristics, joint motion, gait-related kinematics, muscle activation, strength, and gross motor function. It reports zero analysis entries. Numerical outcome estimates and the statistical procedures used for the primary comparison are not reported in the registry record.

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.

Pre-BoNT/ Pre-3DfUS

Reasons for not completing this period:

8-10w Post-BoNT/ 8-10w Post-3DfUS

Analysis population for the primary outcome, as defined in the registry: Semitendinosus: Intervention group: n = 24 \< 25 due to bad quality data Control group: n = 19 \< 20 due to bad quality data

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 in Normalized Muscle Volume of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus, measured over Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group..

The primary endpoint is change in normalized muscle volume of the medial gastrocnemius and the distal compartment of the semitendinosus. The registry describes estimating muscle belly volume with three-dimensional freehand ultrasonography and normalizing that estimate to the product of body weight and height. The listed unit is ml/kg*m. Normalization is intended to express the volume measurement relative to body size, rather than simply compare raw volume measurements across children.

The assessment compares baseline with follow-up between baseline and 8-10 weeks after injections in the intervention group, and between baseline and 8-10 weeks later in the control group. The registry identifies the summary parameter as the median and dispersion as the inter-quartile range. These summaries describe the center and spread of measurements; they do not, on their own, quantify an adjusted treatment effect or establish why groups may differ.

The endpoint is relevant to the study's stated focus on muscle and tendon architecture following treatment. However, the registry does not report the measured baseline or follow-up values, the amount of change, a between-group estimate, or an uncertainty interval. It therefore does not permit a reader to assess the size or precision of the primary endpoint result from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record is limited. It identifies a median as the primary summary parameter and an inter-quartile range as the measure of dispersion. It does not report a statistical analysis plan, a specific test or model, an adjusted analysis, a confidence interval, or p-values. The following explanations describe general statistical concepts, not methods confirmed as having been used in this study.

What do the median and inter-quartile range describe?

In general, the median is the middle value when observations are ordered. It can be useful when measurements are skewed or when extreme values might pull the arithmetic mean away from a typical observation. The inter-quartile range describes the spread of the central portion of the observations, from the lower quartile to the upper quartile. Together, median and inter-quartile range provide a compact description of location and variability. They do not automatically answer whether groups differ, and they do not show how precisely an estimated difference is known.

The record's choice of these summaries does not reveal the distribution of the measurements or the rationale for selecting them. It also does not say whether the reported parameter would apply to baseline values, follow-up values, change scores, or a contrast between groups. The endpoint title refers to change, but the registry does not supply the analysis details needed to determine how that change was statistically summarized or compared.

What would a confidence interval contribute?

In general, a confidence interval expresses uncertainty around an estimate. It gives a range of values compatible with the data and the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, while the interval's position helps readers assess which values remain plausible. A confidence interval is not reported in the registry record for the primary outcome. Without an estimate and its uncertainty, the precision of the comparison cannot be assessed.

A p-value, if reported, would address how compatible the observed data are with a specified null model under the assumptions of the test. It would not measure the size or clinical importance of a difference, nor would it establish causation. No primary-outcome p-value or test is reported in the registry record. Statistical significance therefore cannot be assessed from the record, and a missing p-value should not be interpreted as a non-significant result.

Why does non-random allocation matter?

In general, random allocation helps balance both measured and unmeasured baseline factors across treatment groups, on average. In a non-randomized study, group membership may be related to factors that also influence outcomes. This is called confounding. For example, treatment selection and a child's baseline condition could be related; whether that occurred in this study is not reported in the registry record. Adjustment methods can sometimes address measured differences, but they cannot guarantee removal of unmeasured confounding. The registry does not report whether any adjustment was used.

The record explicitly identifies the allocation as non-randomized and cautions that the arms are not a like-for-like control comparison. This means group differences should be read as comparisons between the observed groups, not as an automatically unbiased estimate of a treatment effect. The allocation process and baseline group characteristics would be important for evaluating the plausibility of alternative explanations, but they are not reported in the registry record.

What does normalization mean?

The muscle volume estimate is normalized to the product of body weight and height. In general, normalization expresses a measurement relative to another quantity, with the goal of making values more comparable across people who differ in body size. It can also change the interpretation of the measure: the endpoint is not simply raw muscle volume, but volume expressed relative to the specified body-size product. The registry describes the method and lists ml/kg*m as the unit, but does not report details of measurement reliability, assessor procedures, or how any ultrasound measurements were quality-checked beyond the note about bad quality data.

What can the planning illustrations tell readers?

The record describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such illustrations are planning scenarios: they show the number of participants per arm associated with specified assumptions. They are not observed power and do not demonstrate that the completed study had a particular probability of detecting an effect. The registry record does not report numerical illustration results or the underlying observed effect estimate. In general, planning outputs depend on assumptions about effect size, variability, allocation, and analysis; they should not be read as a substitute for the actual result.

Overall, the record describes the endpoint and some summary conventions, but not the analysis used to produce a comparative estimate. The number of analysis entries is 0. Details of model specification, handling of repeated measurements, covariate adjustment, hypothesis testing, confidence intervals, and statistical software are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures. Alongside the primary muscle-volume endpoint, the listed outcomes cover additional muscle and tendon measurements, gait-related kinematics, muscle activation, and joint range of motion. Examining multiple outcomes can raise a multiplicity issue: in general, the more statistical comparisons made, the greater the chance that at least one result appears notable by chance alone. How to address that concern depends on the prespecified analysis plan and the role assigned to each outcome. A multiplicity strategy is not reported in the registry record.

The record reports zero analysis entries and does not provide numerical results for the primary or other outcomes. It does not say which outcome comparisons were performed, whether any outcomes were designated as exploratory, or whether statistical tests were adjusted for multiple comparisons. The list of outcomes alone does not establish which analyses were completed or how their results should be interpreted.

For the semitendinosus primary-outcome population, the registry states intervention group n = 24 < 25 and control group n = 19 < 20 due to bad quality data. This documents a data-quality issue affecting the stated counts. The record does not report the measurements that were excluded, the criteria for judging data quality, or whether the same issue affected other outcomes. It also does not describe whether missingness was related to participant characteristics or outcome values, whether any values were imputed, or whether sensitivity analyses were conducted. These details are not reported in the registry record.

The analysis population is not described beyond the endpoint-specific count note. It is therefore unclear from the record whether analyses followed an intention-to-treat approach, included only participants with usable measurements, or used another definition. That uncertainty limits assessment of how missing or unusable data may have influenced the comparison.

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 for the intervention and control groups. In the intervention group, 25 were listed as at risk, with 0 serious adverse events and 0 deaths. In the control group, 20 were listed as at risk, with 0 serious adverse events and 0 deaths. The record also lists 25 at risk for other adverse events in the intervention group and 20 in the control group, with 0 other adverse events in each group. No top serious adverse event terms are listed.

These are the counts recorded in the registry, not proof that no adverse events occurred outside the record's definitions, observation period, or reporting process. The safety follow-up duration and the procedures used to collect or classify adverse events are not reported in the registry record. The counts should therefore be read as registry-reported events for the listed at-risk groups, not as a complete characterization of safety.

Zero recorded events also do not establish that the risks are identical across groups. The study is non-randomized, and the registry does not provide a comparative safety analysis or uncertainty estimates. These figures describe what was entered in the registry; they do not support a broader conclusion about safety or a recommendation for care.

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

The record describes a completed study designed to assess short-term changes in muscle and tendon characteristics and related outcomes following an integrated botulinum toxin treatment approach in children with spastic cerebral palsy. Its primary endpoint concerns normalized muscle volume in the medial gastrocnemius and distal semitendinosus compartment. The intervention group received injections together with post-injection care, while the control group continued usual care.

The registry record does not report numerical outcome results. It gives no group values, change estimates, between-group contrast, confidence interval, or p-value for the primary endpoint. Consequently, it does not establish the direction, size, or precision of any difference in muscle volume. A completed status and a defined endpoint do not reveal the result.

The comparison is non-randomized and the registry cautions that the arms are not a like-for-like control comparison. Any observed group difference would need to be considered alongside possible baseline differences and other sources of confounding. The record does not report the allocation process, baseline characteristics, or statistical adjustment methods. It also does not separate the possible contributions of injections, serial casting, and intensive physical therapy within the integrated approach.

The endpoint is a normalized imaging-based measure, not a complete measure of all aspects of cerebral palsy or treatment response. The registry lists other outcomes related to muscle and tendon properties, joint motion, gait kinematics, muscle activation, and function, but does not report their numerical results. Follow-up was short, with assessments between baseline and 8-10 weeks later, so the study description concerns short-term measurement rather than longer-term outcomes.

The adverse-event entries report zero serious and zero other adverse events in the listed groups, with zero deaths. These registry counts do not by themselves establish the absence of risk, particularly because the observation and reporting details are not given. Overall, the record documents the study question, design, endpoint definitions, and selected safety counts, but does not provide outcome estimates from which to draw conclusions about comparative effects.

13. Why This Trial Matters Statistically

This study raises a statistical question about measuring muscle architecture over a short period in a clinical population, while comparing an integrated intervention with usual care. The primary outcome is not a raw volume measurement: it is normalized to the product of body weight and height. That makes the measurement's scale and interpretation central to understanding any eventual estimate. The registry describes the measurement approach but does not publish the outcome values needed to evaluate it.

The design also illustrates why allocation matters when interpreting clinical comparisons. In a randomized trial, allocation is intended to make groups comparable on average. Here, allocation was non-randomized, and the registry itself warns that the arms are not a like-for-like control comparison. This makes transparent reporting of baseline characteristics, treatment assignment, and adjustment especially important. Those details are not reported in the registry record.

The study description includes a combined package of injections, serial casting, and intensive physical therapy, while usual care includes physiotherapy and orthotic management. A comparison of these groups would address the package as implemented; it would not independently identify the contribution of each component. This distinction matters when translating a group-level result into a claim about a particular treatment element.

The registry lists a broad set of outcome measures, extending beyond the primary imaging measure to movement, activation, and functional domains. Considering multiple outcomes can offer a wider picture of the study question, while also making it important to report which analyses were planned and how multiple comparisons were handled. Those analysis details and numerical results are not reported in the registry record. The record is therefore useful for understanding the intended measurement and design, but not for judging the size or reliability of the findings.

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 record is the absence of numerical outcome results. Although the study is marked completed, the registry does not report the primary endpoint values, changes, between-group estimates, confidence intervals, or p-values. It also reports zero analysis entries, leaving the statistical comparison undocumented in the registry record.

Non-randomized allocation limits causal interpretation. The record does not explain how participants entered each group, provide baseline group characteristics, or report adjustment for potential confounders. It explicitly warns that the arms are not a like-for-like control comparison. Thus, even if comparative results were available elsewhere, the registry information alone would not show whether observed differences could be explained by pre-existing group differences.

The intervention is a package that includes botulinum toxin injections and post-injection care, described as serial casting and intensive physical therapy. The record does not permit the effects of individual components to be separated. The comparator's usual care is described generally as physiotherapy and orthotic management, without further detail about what each participant received.

For the semitendinosus primary-outcome population, the registry notes that bad quality data affected the stated counts: n = 24 < 25 in the intervention group and n = 19 < 20 in the control group. It does not describe the quality criteria, data exclusions, missing-data methods, or analysis population. Outcome-measurement procedures beyond the ultrasound description and the data-quality note are not reported.

Finally, the primary assessment was short-term, between baseline and 8-10 weeks later. Longer-term outcomes, detailed safety observation procedures, eligibility criteria, baseline measurements, and the prespecified statistical plan are not reported in the registry record. These gaps restrict assessment of precision, comparability, and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy — NCT05126693.
• Registry record last updated 2025-07-31; status last verified 2025-05.
• Results first posted 2025-07-31.
• 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

NCT05126693 is a completed, non-randomized, parallel-group study with no masking, sponsored by Universitaire Ziekenhuizen KU Leuven. It enrolled 61 children with spastic cerebral palsy. The intervention combined botulinum toxin injections with post-injection care; controls continued usual care.

The primary outcome was change in normalized muscle volume of the medial gastrocnemius and distal semitendinosus compartment, assessed between baseline and 8-10 weeks later. Volume was estimated by three-dimensional freehand ultrasonography and normalized to the product of body weight and height. The record identifies the median and inter-quartile range as summary measures, but does not report numerical outcome results or analysis details.

The registry lists 17 outcome measures and zero analysis entries. It records zero serious adverse events, zero other adverse events, and zero deaths in the listed intervention and control groups. The non-randomized design, short follow-up, semitendinosus data-quality note, and absence of posted outcome estimates limit interpretation of comparative effects.