Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation (NCT01569607), a randomized na study. The primary outcome is Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve.

2. Clinical Question

The study rationale links motor cortex reorganization with recovery of motor deficits after stroke. Its stated aims were to investigate functional reorganization and structural cortical change, and to explore whether structural changes were related to training-induced functional reorganization. These are research questions, not results: the registry record does not report estimates comparing the randomized arms, uncertainty around such estimates, or evidence resolving those aims.

3. Trial Design

The registry identifies this as a randomized, double-masked, parallel-group study. The listed enrollment was 48, and the study status is completed. The recorded start date is 2012-03-08, and the primary completion date is 2016-08-26. The phase is recorded as NA. The sponsor is Cathrin Buetefisch.

Participants were assigned to Hebbian-type stimulation or sham stimulation. The active arm description specifies motor training with Hebbian-type stimulation; the comparison arm description specifies sham stimulation. Repetitive transcranial magnetic stimulation and sham stimulation are listed as device interventions. The registry record does not describe the randomization sequence, allocation concealment, masking procedures, or which groups of people were masked. It also does not provide enough detail to determine whether the training schedule and other co-interventions were identical across arms.

The primary outcome is mean primary motor cortex excitability derived from a stimulus response curve, measured in millivolts. Measurements were planned at baseline, Post-Training 1 (1 Week), and Post-Training 2 (4 Weeks). The primary outcome description says the analysis was conducted for participants who completed all study procedures. The number included in that analysis and the handling of participants without complete measurements are not reported in the registry record.

Listed secondary outcomes include measures of hand function, wrist movement, motor activity in daily life, and performance on the Wolf Motor Function Test. The registry record lists nine outcome measures, but reports no analysis results for them. The design information therefore establishes the intended comparison and measurement framework, not the effect of the intervention or the precision of any estimated effect.

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: Participants completed the eligibility phase prior to being randomized to a study arm. Of the 48 participants that provided consent, 22 were eligible for participation and were randomized to an intervention.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis was conducted for participants that completed all study procedures.

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: Participants that were randomized to a study arm and received an intervention.

6. Primary Endpoint

The registry lists the primary outcome as Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve, measured over Baseline, Post-Training 1 (1 Week), Post-Training 2 (4 Weeks).

The primary endpoint is mean primary motor cortex (M1) excitability derived from a stimulus response curve, expressed in millivolts. The registry describes motor evoked potential (MEP) amplitudes measured before treatment at baseline, one week after treatment at Post-Training 1, and four weeks after treatment at Post-Training 2. MEPs are elicited by transcranial magnetic stimulation at increased intensity, and their peak-to-peak amplitudes are plotted against stimulation intensity to form the curve.

In general, a stimulus response curve characterizes how a measured response changes as the stimulus intensity increases. The registry rationale states that long-lasting increases in MEP amplitude indicate increased motor cortex excitability and are associated with motor learning. This makes the measure relevant to the stated question about whether training paired with stimulation is accompanied by changes in M1 function. It is a physiological measure, rather than a direct measure of everyday hand use or functional independence.

The endpoint is described as a mean with standard deviation. However, the registry record does not report the arm-specific means, standard deviations, change estimates, or comparisons at the recorded time points. It therefore does not establish whether excitability changed, how large any change was, or how precisely an effect was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to assign participants to study arms in a way that reduces systematic differences between groups at the outset. In general, when allocation is properly implemented, it supports interpreting later group contrasts as estimates of the intervention effect, subject to adherence, missing data, measurement quality, and other design limitations. This study is recorded as randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record. The assignment method therefore cannot be evaluated further from this information.

What does double masking mean?

In general, masking is intended to limit the influence of expectations or knowledge of assignment on care, reporting, measurement, or analysis. The registry classifies this trial as double-masked. It does not specify which participants, investigators, assessors, or other personnel were masked, nor does it describe how the sham procedure was made comparable to active stimulation. The label alone does not establish how masking was implemented or whether it was maintained.

What does a parallel-group comparison estimate?

In a parallel design, randomized groups receive their assigned approaches during the study, and outcomes can be compared between groups. The record identifies a Hebbian-type stimulation arm and a sham-stimulation arm. A between-arm contrast would ordinarily be central to estimating the effect of assignment. No primary outcome contrast is reported in the registry record, so the design description should not be mistaken for a numerical comparison or a finding.

How should the repeated measurements be understood?

The primary endpoint is recorded at baseline and at two post-training occasions: Post-Training 1 (1 Week) and Post-Training 2 (4 Weeks). Repeated measurements can describe outcome patterns over time and can help distinguish a difference at one occasion from a difference that persists across later measurement. In general, an analysis of repeated measurements must account for the fact that observations from the same participant are related. The registry record does not report the model, covariance assumptions, specific contrasts, or analysis results used for these occasions.

The endpoint is a continuous measure summarized as a mean and standard deviation. In general, a mean describes the average observed measurement, while a standard deviation describes variability among observations. A mean difference between randomized arms would express the contrast in the endpoint's measurement scale, millivolts. The posted record does not include the arm-specific summaries needed to interpret such a contrast.

What do uncertainty measures contribute?

In general, a confidence interval communicates the uncertainty around an estimate: a narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. A p-value addresses how compatible the observed data are with a specified null hypothesis under a statistical model; it does not describe the size or clinical relevance of an effect. Neither confidence intervals nor p-values for the primary comparison are reported in the registry record. As a result, no inference about precision or statistical evidence can be made from the listed design information alone.

How should planning calculations be read?

The planning assumptions describe an illustration based on an observed effect, with equal allocation between arms, a normal approximation, and a two-sided significance level of 0.05. The illustration is not the trial's own design justification and is not observed power. In general, a sample-size calculation depends on assumptions about the effect to detect, outcome variability, error rates, and allocation. It can show how those assumptions relate to a hypothetical planning target, but it cannot establish that a completed study had a particular probability of detecting an effect. The calculation values and the effect estimate used for the illustration are not reported in the registry record. No sample size should be inferred from the listed enrollment of 48 alone.

Why can variability matter?

In general, greater outcome variability makes a group contrast harder to estimate precisely when other features remain unchanged. Some continuous outcomes may also have variability that is not well represented by a simple model. Over-dispersion means that observed variability exceeds what a model assumes; accounting for it can affect uncertainty estimates and tests. This is a general statistical consideration, not a reported feature of this trial. The registry record does not report a dispersion assessment or describe model diagnostics.

The primary outcome specifies analysis among participants who completed all study procedures. In general, restricting an analysis to completers can make the analyzed groups differ from the groups originally randomized if completion is related to prognosis or treatment experience. Other strategies, such as analyses that include participants with incomplete data under stated assumptions, may address different estimands and rely on different assumptions. The registry record does not describe such strategies or report the number of participants included in the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measured at baseline, Post-Training 1 (1 Week), and Post-Training 2 (4 Weeks), as well as nine outcome measures in total. Multiple outcomes and measurement occasions create a multiplicity question: if many contrasts are tested, the chance of obtaining at least one apparently unusual result can increase. In general, a prespecified testing strategy or adjustment can address that concern, but the approach depends on the scientific question and analysis plan. A multiplicity strategy is not reported in the registry record.

The record's note that the primary outcome has several categories or time points and was not reduced to one comparison means a single primary comparison is not available in the posted information. The analysis plan, hierarchy of contrasts, and any adjustments for multiple testing are not reported in the registry record. Consequently, the intended basis for a confirmatory claim across time points cannot be assessed.

The primary outcome population is described as participants who completed all study procedures. The registry record does not report the number completing the study, the number with primary outcome measurements at each occasion, reasons for missingness, or how missing measurements were handled. In general, missing data can bias an estimate if the likelihood of missingness is related to outcome values or treatment assignment. Complete-case analysis can also produce a different result from an analysis that includes incomplete records under explicit assumptions.

The record does not report whether the primary analysis followed the randomized assignment regardless of treatment received, whether participants were analyzed according to treatment received, or whether another population was used. It also does not give details of protocol deviations or adherence. These omissions limit assessment of the analysis population and the extent to which the posted analysis, if any, preserves the randomized comparison.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 11 participants at risk for serious adverse events in the Hebbian-type Stimulation arm and 11 in the Sham Stimulation arm. It reports 0 participants affected by serious adverse events in each arm. For other adverse events, the record also lists 11 participants at risk in each arm and 0 affected in each arm. No serious adverse event terms are listed.

These figures describe the registry's recorded counts; they do not by themselves establish that no adverse events occurred outside the recorded categories or reporting window. The time period for adverse-event collection and the methods used to solicit, classify, or attribute events are not reported in the registry record. The death counts are not reported in the registry record.

In general, a count of affected participants is interpreted alongside the number assessed, the observation period, and the event definitions. The listed at-risk counts are safety denominators and should not be treated as the number enrolled or as the primary outcome analysis population. The record lists enrollment of 48, while the safety figures concern 11 participants per arm; the relationship between these populations is not explained. The safety information is therefore limited to the posted counts and does not support broader conclusions about comparative safety.

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

This trial addressed a relevant statistical and scientific question: whether pairing motor training with Hebbian-type stimulation is associated with changes in motor cortex excitability, and whether functional and structural reorganization can be examined in people with stroke. The registry describes a randomized, double-masked, parallel-group design and specifies a physiological primary outcome, together with secondary measures of motor performance and activity.

What the record does not establish is whether the intervention changed the primary outcome or any secondary outcome. No arm-specific result, treatment contrast, confidence interval, or p-value is reported for the outcomes. The study's stated aims and biological rationale must therefore remain distinct from evidence of an observed effect. The registry's completed status is not itself a result.

In general, a statistically detectable difference is not automatically meaningful to patients, and a result that is not statistically detectable does not establish that groups are equivalent. Interpretation depends on the estimated effect, its uncertainty, outcome relevance, study conduct, and analysis choices. Because the registry record does not report the primary estimates or their precision, neither statistical evidence nor clinical importance can be judged from it.

The outcomes cover different concepts. MEP amplitude and the stimulus response curve address a physiological feature of motor cortex excitability. Measures such as hand-task time, wrist movement, motor activity, and motor function address aspects of performance or daily activity. A finding on one kind of measure would not automatically demonstrate a change in another. The registry record does not report the results needed to determine how these measures related to one another.

The record can therefore be read as documentation of a completed trial's question, design, planned outcomes, and limited adverse-event counts. It cannot, on its own, support a claim that Hebbian-type stimulation improved recovery, changed cortical structure, or had no effect. Those conclusions require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

The trial is statistically notable for linking a mechanistic measure with outcomes that address motor performance. M1 excitability derived from a stimulus response curve is the primary endpoint, while the listed secondary measures include hand function, wrist movement, motor activity, and motor function. This combination reflects a distinction that matters in clinical research: a physiological change and a change in patient-relevant function are related questions, but they are not interchangeable outcomes.

The recorded design also makes the comparison itself important. Randomization and masking can reduce some sources of bias when implemented effectively, but the registry provides only the design labels and limited procedural detail. Understanding how assignment was generated, how masking worked, and whether treatment exposure was comparable would help readers assess how strongly a group contrast could be attributed to the assigned approach. Those details are not reported in the registry record.

Repeated outcome measurement creates another statistical issue. Measurements at baseline and at two post-training occasions can address when a change is observed and whether it is sustained across the recorded period. But interpretation depends on the chosen contrasts, handling of within-participant correlation, missing measurements, and multiplicity. The record does not report those analysis details or the results.

Finally, this trial illustrates the difference between a completed study and an interpretable posted result. Enrollment and outcome plans provide context, but they cannot substitute for estimates and uncertainty. The registry record documents a study designed to investigate cortical reorganization after stroke, while leaving the central statistical questions about effect size and precision unanswered.

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 main limitation for interpreting the trial from the registry record is the absence of primary and secondary outcome results. Although the study is marked completed and has a listed enrollment of 48, no outcome estimates, between-arm comparisons, confidence intervals, or p-values are reported. The direction, size, and precision of any treatment effect therefore cannot be assessed.

The primary outcome description specifies analysis among participants who completed all study procedures, but the number completing those procedures is not reported. The record does not describe missing measurements, reasons for discontinuation, or methods for handling incomplete outcomes. It also does not state whether analyses followed randomized assignment or used another population.

The primary endpoint includes multiple measurement occasions, and the registry notes that it was not reduced to one comparison. The analysis plan for those occasions, including contrast selection and any multiplicity approach, is not reported. This makes it difficult to know which comparison was intended to carry the primary inference.

Further design details are limited. The registry does not report the randomization method, allocation concealment, the identities of those masked, or how sham stimulation was implemented. It does not provide enough information to establish whether the training experience was matched between arms. The duration and procedures for adverse-event collection are also not reported, and death counts are not reported in the registry record.

These limitations describe gaps in the posted information, not proof of shortcomings in how the trial was conducted. They constrain what can be concluded from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation — NCT01569607.
• Registry record last updated 2018-01-16; status last verified 2017-12.
• Results first posted 2018-01-16.
• 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

NCT01569607 is a completed, randomized, double-masked, parallel-group study with listed enrollment of 48. It compared motor training with Hebbian-type stimulation against sham stimulation in people with stroke. The primary outcome was mean M1 excitability derived from a stimulus response curve, measured in millivolts at baseline, Post-Training 1 (1 Week), and Post-Training 2 (4 Weeks). The registry also lists nine outcome measures, including assessments of hand function, wrist movement, motor activity, and motor function.

The record lists 11 participants at risk in each arm for serious and other adverse events, with 0 affected in each category. Primary and secondary outcome results, analysis details, and the primary analysis sample size are not reported in the registry record. The study's completed status and planned outcomes do not establish an observed treatment effect.