Altering Activation Patterns Post-stroke: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Altering Activation Patterns Post-stroke (NCT02418949), a randomized na study. The primary outcome is Change in Mean Completion Time for Graded Wolf Motor Function Test (GWMFT).

2. Clinical Question

3. Trial Design

Altering Activation Patterns in the Distal Upper Extremity After Stroke (NCT02418949) was a randomized, parallel-group trial. The record describes the masking as quadruple. It lists Shirley Ryan AbilityLab as the sponsor, gives the study status as completed, and reports enrollment of 96. The recorded start is 2015-11, and primary completion is 2019-08. The phase is listed as NA.

There were four treatment combinations: cyproheptadine with Active Movement Practice (AMP), placebo for cyproheptadine with stretching, cyproheptadine with stretching, and placebo for cyproheptadine with AMP. The primary endpoint was evaluated at baseline and 9 weeks, immediately post intervention. The record describes the study as a rehabilitation approach for stroke survivors in the chronic phase of recovery, combining drug therapy and active movement practice to encourage voluntary muscle control and strength.

The reported primary-outcome sample counts are 20 for cyproheptadine plus AMP, 21 for placebo plus stretching, 23 for cyproheptadine plus stretching, and 24 for placebo plus AMP. These are the arm counts attached to the outcome estimates; they should not be treated as a breakdown of all enrolled participants without further information. The registry record does not report the randomization ratio, the details of who was masked, or a full account of treatment and follow-up procedures.

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

Reasons for not completing this period:

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: 1 Participant in "Cyproheptadine + AMP" \& 1 Participant in "Cyproheptadine + Stretching" did not continue past enrollment to baseline assessment

6. Primary Endpoint

The registry lists the primary outcome as Change in Mean Completion Time for Graded Wolf Motor Function Test (GWMFT), measured over baseline and 9 weeks (immediately post intervention).

The primary endpoint is change in mean completion time for the Graded Wolf Motor Function Test (GWMFT), measured in seconds. The assessment comprises 15 timed tasks focused on upper-extremity function. Each task has a maximum allowable time of 120 seconds. The recorded timeframe is baseline and 9 weeks, immediately post intervention.

A timed task measure captures how long a participant takes to complete the specified activities. In general, a shorter completion time represents faster task performance, while the change from baseline describes how the mean time shifted over the assessment period. The posted values are negative in all four arms, indicating decreases in mean completion time as expressed by the reported change. That description does not by itself establish that one assigned regimen performed better than another: the arm-level changes are not direct between-arm contrasts.

The GWMFT was used as a clinical measure focused on upper-extremity function. The registry record identifies it as the primary outcome but does not report a threshold for interpreting the size of a change as important to participants, or additional details about the scoring procedure beyond the timed tasks and maximum allowable time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a mean change in completion time, measured in seconds. The registry identifies the parameter as a mean and the uncertainty measure as a 95% confidence interval. The figures therefore describe an estimated average change for each arm, accompanied by an interval reflecting its statistical uncertainty. They are not individual participant ranges.

In general, a confidence interval is constructed using an estimate and a measure of its variability under a statistical model. A narrower interval indicates greater precision under that method; a wider interval indicates greater uncertainty. The arm-specific intervals reported for this trial overlap substantially. Overlap between separate arm-level intervals is not a formal test of the difference between arms. To answer a comparative question, the relevant quantity is the difference in mean change between randomized groups, with a confidence interval or other inferential result for that contrast. Such estimates are not reported in the registry record.

The reference to change from baseline means that the reported endpoint concerns a shift in mean completion time between baseline and the 9-week assessment. In general, using a baseline measure can help describe change over time, but the registry summary does not state how baseline values were incorporated in the analysis. It does not report whether the analysis used a model adjusted for baseline, a repeated-measures method, or a simple calculation of change scores. Those details are not reported in the registry record and should not be inferred from the outcome label.

Randomization is intended to support fair comparisons by assigning participants to treatment groups through a chance process. The trial is described as randomized and parallel, but the registry record does not describe the allocation procedure, stratification factors, or any concealment procedures. It also does not specify the identities of those included in quadruple masking. The design labels describe important features, but they do not provide the full analysis methods.

The primary outcome estimates are reported for 20 participants in cyproheptadine plus AMP, 21 in placebo plus stretching, 23 in cyproheptadine plus stretching, and 24 in placebo plus AMP. The record does not say whether these counts represent all randomized participants with available outcomes, a particular analysis population, or another subset. Enrollment of 96 is not the same as an analysis count, and no additional analysis-population description is reported.

The registry reports no posted analyses. It gives arm-level outcome summaries but no inferential comparison for the primary endpoint. There is no reported analysis plan describing the model, its assumptions, handling of repeated measurements, or the procedure used to calculate the confidence intervals. These omissions limit how fully the statistical analysis can be assessed from the registry record.

Planning illustrations based on the observed effect use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such illustrations are conditional planning calculations, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the trial's own sample-size justification. No resulting planning counts are discussed as trial observations.

In general, statistical comparisons across multiple arms and outcomes raise questions about multiplicity. The registry identifies one primary outcome and one posted secondary outcome, but does not report whether any multiplicity adjustment was planned or applied. Likewise, the record does not describe interim analyses. These are unknown features of the analysis, not grounds for assuming a particular method.

General statistical interpretation also depends on how missing outcome measurements are handled. The registry record does not report a missing-data strategy, the amount or reasons for missing primary outcomes, or whether sensitivity analyses were performed. Without those details, the arm-level estimates can be read as the posted summaries, but the possible influence of missing data cannot be evaluated from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies the change in mean GWMFT completion time as the primary outcome and lists change in Grip Relaxation Time following a Maximum Voluntary Contraction as a secondary outcome. It reports two outcome measures, while one secondary outcome is posted. The record does not describe a multiplicity strategy, such as whether the primary endpoint alone was treated as confirmatory or whether adjustment was planned across outcomes or treatment comparisons. No adjustment should be assumed.

The registry record does not report a missing-data method, the number of missing primary outcome measurements, reasons for missingness, or sensitivity analyses. It also does not identify the analysis population used to produce the arm-level estimates. The outcome counts are available, but the record does not explain how participants without an observed endpoint were handled. These details matter because an analysis based only on observed outcomes may be affected if outcome availability is related to assigned treatment or participant status; the record does not give enough information to assess that possibility.

The record reports no analyses, and does not give an interim-analysis plan or the statistical plan for the primary comparison. It is therefore not possible to determine from this record whether there were prespecified analysis populations, how multiplicity was addressed, or whether any interim review affected the analysis. These aspects are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsions (4.5%), coronary blockage (4.5%), bowel obstruction (4.3%), pneumonia (4.3%), foot wound (4.3%).

The safety summaries report serious adverse events and other adverse events separately by arm. For serious adverse events, the record gives both the number at risk and the number affected. Cyproheptadine plus AMP had 2 affected among 23 at risk; placebo for cyproheptadine plus stretching had 2 among 22; cyproheptadine plus stretching had 1 among 26; and placebo for cyproheptadine plus AMP had 0 among 25. The record reports 0 deaths in each arm.

For other adverse events, the corresponding figures were 19 among 23 at risk for cyproheptadine plus AMP, 15 among 22 for placebo plus stretching, 18 among 26 for cyproheptadine plus stretching, and 21 among 25 for placebo plus AMP. These are arm-level counts as reported, not estimates of causal risk differences. The record does not provide an adjusted safety comparison or enough detail to infer whether events were related to a study intervention.

The listed serious-event terms include Convulsions (4.5%), Coronary Blockage (4.5%), Bowel Obstruction (4.3%), Pneumonia (4.3%), Foot Wound (4.3%), and CHF Exacerbation (3.8%). Their context and denominators are not further described in the registry record. The counts and terms should be read as descriptive safety reporting, not as evidence that a particular regimen caused or prevented an event.

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

The results describe the observed arm-level mean changes in GWMFT completion time from baseline to 9 weeks. All four reported changes are negative, meaning the estimated mean completion time decreased within each arm. The 95% confidence intervals communicate uncertainty around those estimates: three include zero, while the interval for cyproheptadine plus stretching lies below zero. This is a description of within-arm change, not proof that any one regimen is superior to another.

The primary comparative question is whether the change differs among treatment combinations. The registry record does not report the necessary between-arm estimates, confidence intervals, or p-values. Similar-looking arm means, or one interval excluding zero while others include it, do not substitute for a direct statistical comparison. Differences in precision between arms can also affect the appearance of their separate intervals.

The reported values do not establish the clinical importance of the changes. The record gives the endpoint definition and units but does not state a threshold for a meaningful difference. It also does not describe the analysis population, missing data, or adjustment for baseline and other factors. Those gaps constrain conclusions about both the magnitude and the reliability of the findings.

The safety summaries give counts of serious and other adverse events and report no deaths in the four arms. They do not provide causal attribution or comparative safety estimates. Overall, the registry record supports a descriptive account of the posted outcomes, but not a conclusion about which combination is preferable or whether any combination changes outcomes relative to another.

13. Why This Trial Matters Statistically

This trial is statistically notable for its four-arm structure, which combines two medication assignments with two forms of movement practice. That design creates several possible treatment comparisons. However, the registry's posted primary results are arm-specific changes rather than estimates of the contrasts that would answer whether the medication, the practice type, or their combination altered the outcome. The distinction between a group mean and a between-group effect is central when interpreting randomized trials.

The confidence intervals also make precision visible. The reported estimates vary in their uncertainty, and three intervals include zero. A result in one arm that is more compatible with a change away from zero does not, on its own, show a difference from another arm. Formal comparison requires a direct contrast and its uncertainty, rather than comparing whether separate intervals include zero.

The record reports 96 enrolled participants but outcome counts by arm, without a stated analysis population or missing-data approach. That leaves important questions about who contributed to the estimates unanswered. Similarly, the outcome and safety summaries do not replace a reported statistical plan, multiplicity approach, or direct treatment-comparison analysis.

The trial therefore illustrates why statistical interpretation depends on both estimates and the form in which they are reported. A mean change can describe what happened within an arm, while a randomized treatment effect is a comparison between arms. Keeping those quantities distinct prevents the descriptive summaries from being read as stronger comparative evidence than the registry record presents.

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.

Several trial-specific limitations of interpretation follow from the registry record. The main posted primary results are means and confidence intervals within each arm; direct randomized contrasts are not reported. The record therefore does not provide the estimates needed to compare the four combinations statistically. It also does not report p-values for those comparisons.

The record lists an enrollment of 96, while the primary outcome summaries have arm-specific counts of 20, 21, 23, and 24. It does not explain the relationship between enrollment and these outcome counts, identify the analysis population, or report the amount and reasons for missing outcome data. The possible effect of missing observations cannot be assessed.

Further details of the statistical plan are not reported in the registry record. These include the model used for the primary endpoint, any baseline adjustment, the handling of multiple comparisons, and any interim analyses. The record does not give a sample-size justification for the trial; planning illustrations based on an observed effect should not be interpreted as the trial's design rationale.

The primary endpoint is timed task performance, but no threshold for a clinically meaningful change is reported. The posted safety summaries are descriptive and do not include causal attribution or comparative estimates. These limitations do not invalidate the reported summaries, but they restrict conclusions about comparative effects, clinical importance, and safety differences among regimens.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Altering Activation Patterns Post-stroke — NCT02418949.
• Registry record last updated 2026-03-31; status last verified 2026-03.
• Results first posted 2021-07-13.
• 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

NCT02418949, titled Altering Activation Patterns in the Distal Upper Extremity After Stroke, is recorded as a completed randomized, quadruple-masked, parallel trial sponsored by Shirley Ryan AbilityLab. Enrollment was 96. The study compared cyproheptadine or placebo paired with AMP or stretching in stroke survivors in the chronic phase of recovery.

The primary outcome was change in mean GWMFT completion time from baseline to 9 weeks, immediately post intervention. The registry reports arm-level mean changes with 95% confidence intervals and outcome counts, as well as serious and other adverse event counts. It does not report direct treatment-comparison estimates, a detailed statistical plan, missing-data methods, or analysis populations. The posted results therefore support descriptive interpretation of changes within arms, but do not provide a statistical comparison of the regimens.