Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury (NCT03100370), a randomized na study. The primary outcome is Fugl-Meyer Arm (FMA) Motor Score.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, triple-masked crossover study of transcutaneous spinal direct current stimulation combined with robotic-assisted arm training in adults with acquired brain injury. The listed conditions are anodal stimulation with training, cathodal stimulation with training, and sham stimulation with training. Listed treatment sequences vary the order in which these conditions are received. In a crossover design, participants may receive more than one condition, so an arm label can refer to a sequence rather than an independent group of people. The registry record does not provide enough detail to reconstruct how each participant’s sequence related to the posted outcome summaries.

The brief summary describes 20 minutes of stimulation at 2.5 milliamps, combined with high-intensity robotic-assisted arm training five days a week for 2 consecutive weeks. The arm descriptions specify the cervical spine as the stimulation site. Some sequence descriptions identify the stimulation condition, while other listed sequences have no accompanying description. Details about the treatment periods, interval between periods, or handling of possible carryover are not reported in the registry record.

The study is marked terminated. Enrollment is reported as 9, while the primary outcome description says data were collected for 7 participants in each arm. In a crossover study, these arm-level figures should not be interpreted as separate, non-overlapping groups or added together to infer the number of participants. The registry record does not explain the relationship between enrollment and the outcome-specific counts.

The reported primary measure is a baseline Fugl-Meyer Arm Motor Score, rather than a change score or a post-treatment measurement. Although the study’s stated purpose is to compare stimulation polarities alongside training, no inferential analyses are posted for the primary outcome. The reason for termination and the reason no comparative analyses appear 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.

First Intervention (2 Weeks)

Reasons for not completing this period:

Washout (30 Days)

Second Intervention (2 Weeks)

Washout (30 Days)

Analysis population for the primary outcome, as defined in the registry: Data were collected for 7 participants in each arm

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: Baseline characteristics data were collected for all 9 participants that were enrolled. 8 of the 9 participants were assigned to and received any intervention.

6. Primary Endpoint

The registry lists the primary outcome as Fugl-Meyer Arm (FMA) Motor Score, measured over baseline.

The primary measure is the Fugl-Meyer Arm Motor Score, an impairment measure for the upper limb. The registry describes it as a stroke-specific, performance-based index grounded in the sequential stages of motor return described by Twitchell and Brunnstrom. It scores 33 upper-limb items on an ordinal scale: 0 means the task cannot be performed, 1 means it can be performed partially, and 2 means it can be performed fully. The stated total range is 0-66, with 0 described as poor and 66 as normal.

A structured performance measure can describe upper-limb motor impairment in a consistent way, while the item scores retain ordered categories rather than representing equal increments by definition. The registry identifies the score as a mean with standard deviation and reports it at baseline. A mean gives a summary of the recorded scores, while the standard deviation describes how dispersed those scores are around the mean. The scale description helps readers understand what the score represents; it does not establish that a change in score occurred.

For the clinical question about stimulation conditions, a baseline score alone cannot indicate whether scores differed after treatment or whether any condition was associated with a change. The registry record does not report a post-treatment Fugl-Meyer comparison, a change from baseline, or a primary endpoint analysis. It also does not report a threshold for interpreting the clinical importance of a score difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists the primary measure as a continuous outcome summarized by a mean and standard deviation. That choice describes the format of the reported summary, not necessarily the full statistical model used to compare treatment conditions. The registry record does not report a primary outcome analysis, model specification, treatment contrast, or inferential test. The distinctions below are general statistical explanations and should not be read as claims about analyses that were conducted for this trial.

What does a mean and standard deviation describe?

A mean is a measure of the center of a set of scores. A standard deviation describes how much scores vary around that center. These summaries can be useful for describing the baseline Fugl-Meyer scores, but they do not by themselves give the uncertainty around a comparison between conditions. The reported standard deviations are not standard errors or confidence intervals. Treating them as if they were would misstate what the registry reports.

The Fugl-Meyer score is composed of ordinal item ratings. Summing ordered item scores produces a total that is often summarized using means and standard deviations, as this registry does. That reporting format does not change the underlying item-level scoring description, and it does not show whether the statistical assumptions for a particular comparative analysis were assessed. Such assessments are not reported in the registry record.

Why does the crossover design matter?

In a crossover design, the same participant may receive multiple conditions at different times. Observations from that participant are therefore related rather than independent. A comparative analysis would generally need to account for this within-participant relationship. It may also need to consider treatment sequence and period, and whether effects from an earlier condition could persist into a later period. These are general considerations for crossover studies; the registry record does not report the model or procedures used to address them.

The listed sequences differ in the order of anodal, cathodal, and sham stimulation with training. The posted baseline summaries do not identify a sequence-specific analysis or show how observations across conditions were paired within participants. It would therefore be inappropriate to treat the three arm summaries as if they necessarily came from separate randomized groups. The outcome description reports 7 participants in each arm, while enrollment is listed as 9, and the record does not explain this presentation.

What can a confidence interval add?

In general, a confidence interval gives a range of estimates compatible with the data under the chosen method and its assumptions. It communicates precision as well as direction and size. A narrow interval indicates greater precision than a wide interval, all else equal, while an interval spanning values on both sides of a null contrast may leave the direction of the effect uncertain. These are general principles; no confidence interval for a primary treatment contrast is reported in the registry record.

A p-value, in general, describes how surprising data at least as incompatible with a specified null hypothesis would be under that hypothesis and the analysis assumptions. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. No primary comparison p-value is posted. The baseline summaries alone cannot be used to infer one.

Why can over-dispersion matter?

Over-dispersion is a general issue when the observed variability in data is greater than a model assumes. If a model understates variability, standard errors can be too small and uncertainty can appear narrower than it is. This concern is most directly discussed for count outcomes or other models with a specified variance structure; the primary endpoint is a score summarized as a mean and standard deviation. The registry record does not report a model or a variance assessment, so over-dispersion should not be asserted as a problem in this trial.

How should sample-size illustrations be understood?

Planning calculations are not observed power and do not recover the trial’s original design rationale. The stated planning assumptions describe an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also specify that the effect to detect is a stated fraction of the observed effect. These assumptions are general planning inputs, not evidence that the trial used them prospectively.

The record indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Consequently, no planning illustration based on a comparative effect can be interpreted as an estimate of the trial’s achieved power. The sample-size justification, if any, is not reported in the registry record. The trial’s enrollment figure should not be used to infer the rationale for its design.

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("tsDCS- Anodal Stimulation & Robotic Arm Training (", "tsDCS- Cathodal Stimulation & RAT", "tsDCS- Sham Stimulation & RAT")
n   <- c(7, 7, 7)
m   <- c(42, 40, 42.8)
sp  <- c(13.8, 12.8, 12.7)
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  tsDCS- Anodal Stimulation & Robotic Arm Training (  7  42.000  13.800  29.237  54.763
CARM  tsDCS- Cathodal Stimulation & RAT  7  40.000  12.800  28.162  51.838
CARM  tsDCS- Sham Stimulation & RAT  7  42.800  12.700  31.054  54.546

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies 28 outcome measures and reports 25 secondary outcomes. The primary measure is the baseline Fugl-Meyer Arm Motor Score. The record does not report a multiplicity strategy, such as a hierarchy of outcomes, an adjustment across comparisons, or a designated primary contrast among the stimulation conditions. Without that information, the effect of multiple testing on any interpretation of secondary results cannot be assessed.

The record lists several secondary measures, including the Jebsen Taylor Hand Function Test, Action Research Arm Test, Motor Activity Log, pinch strength, and quantitative movement measurement. It also lists participants with adverse effects related to stimulation as an outcome. The presence of multiple outcomes creates a general interpretive concern: considering many comparisons can make chance findings more likely unless the analysis plan addresses multiplicity. This is a general statistical point, not a claim that a particular false-positive result occurred in this trial.

No analyses are posted for the primary endpoint. The registry record does not report an analysis population, a missing-data method, or how unavailable measurements were handled. It also does not report whether all randomized participants completed each treatment period or provide a participant flow account that would explain the outcome-specific counts. The enrollment figure and the per-arm data collection statements should therefore be read as separate reported details, not reconciled by assumption.

In a crossover study, missing observations can affect paired comparisons differently from analyses of independent groups. If a participant lacks measurements for a condition or period, the available within-participant information may be incomplete. This is a general design consideration; the registry record does not say whether such missingness occurred or how it was treated. It also does not report an intention-to-treat or other analysis-population definition.

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.

The adverse-event entries list zero serious events, zero other adverse events, and zero deaths for the anodal stimulation with robotic arm training condition, the cathodal stimulation with training condition, and the sham stimulation with training condition. Each entry reports 7 participants at risk for the serious and other event summaries. These are the counts in the registry record; they should not be read as a guarantee that no event occurred outside the recorded definitions or reporting period.

The registry lists an outcome concerning participants with adverse effects related to transcutaneous spinal direct current stimulation. The posted group summaries report zero affected participants in each category. The record does not give serious adverse event terms, and it does not provide further detail about event definitions, monitoring procedures, exposure duration, or the timing of safety assessments. Those details are not reported in the registry record.

Zero recorded events in these entries is a descriptive finding, not proof that the conditions carry no risk. Safety estimates based on a small study may be imprecise, and the crossover design means group labels do not necessarily represent independent sets of participants. The registry’s figures should be interpreted as the event counts it records for the listed conditions, not as a broad safety conclusion.

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

The registry record describes a randomized, triple-masked crossover study of anodal, cathodal, and sham transcutaneous spinal direct current stimulation paired with robotic-assisted arm training. Its primary outcome entry reports baseline Fugl-Meyer Arm Motor Scores, summarized as means and standard deviations. The reported values describe the participants’ baseline scores in the listed conditions; they are not measurements of improvement following a condition.

The primary outcome results do not establish whether either active stimulation polarity changes upper-limb motor impairment, whether an active condition differs from sham, or whether the conditions produce equivalent results. The record does not report a post-treatment primary outcome comparison, an estimated treatment effect, a confidence interval, or an inferential test. It therefore does not support a conclusion about the comparative effect or precision of the stimulation conditions.

The study status is terminated. The reason for termination is not reported in the registry record. The posted safety entries show zero serious events, zero other events, and zero deaths in each listed condition, but those records do not demonstrate the absence of all possible adverse effects or quantify safety with high precision.

More broadly, the absence of posted comparative analyses should not be interpreted as evidence that the interventions have the same effect, nor as evidence that one is superior. It means the registry record, as reported, does not supply the analysis needed to answer that question. The posted baseline and safety summaries remain descriptive information, with limits on what can be inferred from them.

14. Why This Trial Matters Statistically

This trial illustrates why the design and timing of an outcome matter as much as its name. The Fugl-Meyer Arm Motor Score is relevant to upper-limb impairment, but the posted primary measure is explicitly at baseline. A baseline score can characterize participants before treatment; it cannot by itself show the change associated with a treatment period or the contrast between stimulation conditions.

The crossover structure also makes a simple reading of arm summaries potentially misleading. When participants can receive multiple conditions, observations are linked within people and can reflect treatment sequence or period. A suitable comparison needs to represent those relationships. Because the registry record does not report such a model or a comparative analysis, the baseline summaries cannot substitute for it.

The record further shows why enrollment and outcome-specific counts need contextual explanation. Enrollment is 9, whereas the primary outcome description reports 7 participants in each arm. In a crossover trial, these statements cannot be resolved by adding arm counts or assuming independent groups. The record does not explain the counts, underscoring the importance of clear participant flow and analysis-population reporting.

For biostatistical interpretation, the case highlights the difference between descriptive summaries and evidence about a treatment contrast. It also shows the value of reporting methods for missing data, multiplicity, crossover effects, and uncertainty. These details are not reported in the registry record for the primary comparison, limiting the conclusions that can be drawn even though means, standard deviations, design, and safety counts are available.

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.

The central limitation is that the primary outcome is reported at baseline, with no post-treatment comparison or change analysis. The registry record does not provide an estimated contrast between anodal, cathodal, and sham stimulation, nor does it report an uncertainty interval or inferential test. The posted results therefore do not answer the trial’s comparative question.

The record identifies a crossover design and lists multiple treatment sequences, but it does not report the analysis model, handling of sequence and period, or assessment of possible carryover. Some sequence descriptions lack intervention details. The relationship between enrollment of 9 and the statement that data were collected for 7 participants in each arm is also not explained. These reporting gaps prevent a fuller assessment of how the design and outcome data relate.

The registry record does not report the reason for termination, a sample-size justification, a missing-data approach, or an analysis-population definition. It does not report a multiplicity plan for the numerous outcome measures. Planning assumptions are described, but the record notes that values are missing or not estimable for a two-arm comparison of the continuous primary endpoint. Those assumptions cannot be treated as the trial’s prospective design rationale or as evidence of observed power.

Finally, the adverse-event entries are descriptive counts, and the registry record does not supply further detail about event definitions, monitoring, or assessment timing. The small outcome-specific counts and absence of comparative analysis limit precision and generalizability. These limitations concern what the registry record reports; they do not establish why the study ended or what unreported analyses may have been conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury — NCT03100370.
• Registry record last updated 2023-05-25; status last verified 2023-05.
• Results first posted 2023-05-25.
• 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

The registry record describes a randomized, triple-masked crossover study of anodal, cathodal, and sham transcutaneous spinal direct current stimulation combined with robotic-assisted arm training in adults with acquired brain injury. It reports enrollment of 9 and a terminated status. The primary outcome is the baseline Fugl-Meyer Arm Motor Score, summarized as a mean and standard deviation, with data reported for 7 participants in each arm.

No primary comparative analysis is posted. The record does not report a post-treatment contrast, confidence interval, or inferential test, and the reason for termination is not reported in the registry record. Safety summaries list zero serious events, zero other events, and zero deaths in each condition. The primary outcome values should therefore be read as descriptive baseline information, not evidence about treatment effects.