Can Transcranial Direct Current Stimulation Improve Ambulation and Fatigue Resistance in People With MS?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Can Transcranial Direct Current Stimulation Improve Ambulation and Fatigue Resistance in People With MS? (NCT02987621), a randomized na study. The primary outcome is Leg Muscle Strength With and Without tDCS..

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, crossover study with an enrollment of 14. In a crossover design, participants receive more than one study condition, so each participant can contribute observations under both the intervention and comparator. This allows a comparison within the same person, although interpretation depends on the conduct and analysis of the repeated sessions. The registry identifies two treatment sequences: sham first, followed by tDCS, and tDCS first, followed by sham.

The sequence descriptions specify a minimum of 7 days between the sham and tDCS sessions and describe the order as counterbalanced. The record does not report how many participants were assigned to each sequence, how randomization was generated, or how allocation was concealed. It identifies masking as single, but does not state which people involved in the study were masked.

The registry status is completed. The recorded study start is 2016-11 and primary completion is 2018-06. The sponsor is Colorado State University. The registry record describes testing of leg muscle strength and fatigue resistance, with tDCS compared with sham. The brief summary describes two groups performing different tasks, while the primary outcome description specifies a crossover comparison for knee extensor strength. Further details resolving how participants were assigned to task procedures are not reported in the registry record.

The registry lists three outcome measures and no posted analyses. The primary outcome is leg muscle strength with and without tDCS; the record’s description includes maximal voluntary contractions and a sustained endurance task. No numerical primary outcome results are reported. The protocol’s rationale, a formal sample-size justification, and a detailed statistical analysis plan 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Crossover design

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: Crossover study

6. Primary Endpoint

The registry lists the primary outcome as Leg Muscle Strength With and Without tDCS., measured over At session 1 and minimum of 7 days later.

The primary endpoint is leg muscle strength measured in Newtons. The registry identifies the outcome parameter as a mean and reports standard error as the dispersion measure. The stated timeframe is at session 1 and a minimum of 7 days later. The comparison is between tDCS and sham stimulation in a crossover design.

The endpoint description says that knee extensor strength was tested with tDCS, described as less than 10V, and sham stimulation at 0V. Participants performed maximal voluntary contractions to identify the weaker leg as the more-affected leg; this was confirmed by self-report and used for the subsequent endurance task. The description also includes a sustained isometric contraction at 15% MVC until the participant voluntarily stopped, followed immediately by a post MVC. These details describe the testing procedures, but the registry does not give the observed strength values or state how the repeated measurements were combined into the primary analysis.

In general, a force measure expressed in Newtons provides a quantitative outcome that can be compared across study conditions. The clinical rationale in the registry is to examine leg muscle function in people with multiple sclerosis. However, the registry record does not establish that a change in this measure corresponds to a specific level of meaningful functional benefit. Without the condition-specific results and an estimate of the contrast, the magnitude and precision of the primary outcome cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, single-masked crossover design. Randomization concerns the assignment of participants to treatment sequences; in this study the listed sequences were sham followed by tDCS and tDCS followed by sham. The registry does not report the randomization method, allocation concealment, or the number assigned to each sequence. Single masking is recorded, but the identity of the masked party is not reported in the registry record.

What does a crossover comparison involve?

In general, a crossover study compares conditions within participants, rather than treating every observation as independent. Each participant may contribute a measurement during the tDCS condition and a measurement during the sham condition. An analysis that accounts for this pairing can use information about within-participant differences. The registry record does not report the statistical model or test used, nor does it give paired differences or a condition contrast.

The sequence matters because participants receive the conditions in an order. The listed sequences reverse which condition comes first, and the record describes the order as counterbalanced. A minimum of 7 days between sessions is stated. In general, a washout interval is intended to reduce the possibility that effects of an earlier condition influence later measurements. The record does not report evidence about carryover, a test of period effects, or an analysis accounting for treatment sequence. The existence of an interval alone does not demonstrate that carryover was absent.

How should the mean and standard error be read?

The primary outcome is specified as a mean, with standard error as the dispersion measure. In general, a mean describes the average observed value in a group or condition. Standard error describes the uncertainty in an estimated mean, rather than the spread of individual participant values. It is therefore distinct from a standard deviation. The registry record gives the intended summary format but does not report the actual means or standard errors, so those quantities cannot be interpreted for this study.

In general, a comparison between two condition means is most informative when paired with an estimate of the difference and its uncertainty. A confidence interval can show the precision of that contrast, while an inferential test may address compatibility with a null hypothesis. Neither a contrast estimate nor a confidence interval or test result is reported in the registry record. No statistical method should be inferred from the outcome’s mean and standard error labels alone.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If it is not handled appropriately, standard errors and inferential results may be too optimistic. This is a general consideration, not a reported feature of this study. The registry does not provide participant-level results or enough distributional information to assess over-dispersion, and it does not report whether any adjustment was considered.

What does a planning illustration mean?

The registry’s stated planning assumptions describe illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not findings from the trial. The registry record does not report a sample-size justification for the trial, and it does not provide the primary outcome estimate needed to interpret a planning calculation based on an observed effect. No planning count should be read as the number enrolled or as evidence about the study’s results.

The registry lists no posted analyses. It does not report whether the primary comparison was adjusted, whether repeated measurements were analyzed with a particular model, or whether any assumptions were checked. Those details are not recoverable from the measurement descriptions alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but provides no posted analyses and does not report a statistical analysis plan. It does not identify which outcomes, beyond the listed primary measure, were included in any inferential testing or how multiple comparisons were handled. When several outcomes or contrasts are tested, multiplicity can increase the chance of at least one apparently unusual result under a null model. In general, a prespecified strategy can clarify whether and how results are adjusted or prioritized. No such strategy is reported in the registry record.

The record does not report a missing-data method, an analysis population, or whether all 14 enrolled participants contributed measurements under both conditions. It also does not state how incomplete sessions, withdrawals, or unusable measurements were handled. In a crossover study, missing one condition can affect whether a participant contributes to a paired comparison. The registry’s enrollment count alone does not establish the number analyzed for the primary endpoint.

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not a reported trial analysis plan or evidence of adequate power. The record does not report a formal sample-size justification, the assumed effect used for the original design, or an analysis population definition. The actual analysis choices and their implications for multiplicity and missing observations 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 0% reporting threshold.

The adverse-event record lists four condition-specific groups: leg muscle strength with tDCS, leg muscle strength with sham, leg muscle endurance with tDCS, and leg muscle endurance with sham. For each listed group, 14 participants were at risk for serious adverse events and 14 were at risk for other adverse events. The registry records zero affected participants for each category in every group, and zero deaths in each group.

These figures describe what was entered in the registry for the listed study conditions. They do not provide event descriptions because no serious adverse-event terms are listed. The record also does not give further detail about how adverse events were defined, collected, or reviewed, or how complete the follow-up was for each participant.

In general, an observed count of zero does not establish that an event is impossible or that a treatment is free of risk. A small study may provide limited information about uncommon events, and the registry does not report enough detail to characterize the completeness of safety surveillance. The figures should therefore be read as the recorded event counts in this study, not as a general safety conclusion.

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

The record establishes that a completed randomized, single-masked crossover study enrolled 14 people with multiple sclerosis and compared tDCS with sham stimulation. It describes the primary measure as mean leg muscle strength in Newtons, with standard error as the dispersion measure, and gives procedural details for the stimulation and testing sessions. These registry entries define the research question and its measurement context.

The record does not report numerical primary outcome results. There is no condition-specific mean, standard error, estimated contrast, confidence interval, or p-value. As a result, it is not possible from the registry record to determine the observed direction or magnitude of the strength difference, or how precisely it was estimated. The trial title and stated rationale are not substitutes for results.

In general, a statistically detectable difference and a practically meaningful difference are distinct questions. Assessing either requires results and a context for interpreting the size of the measured change. The registry does not report a threshold for a meaningful strength difference or link the measured outcome to a functional threshold. It also does not report results for the other listed outcomes.

The crossover design means that the intended comparison uses repeated observations from participants under both stimulation conditions. In general, this can make within-person contrasts informative, but the interpretation depends on complete measurements and suitable analysis of pairing, sequence, and period. Those analysis details and the number of participants with usable data are not reported. The record therefore supports a description of what was intended and how it was measured, not an estimate of efficacy, effectiveness, or clinical importance.

The safety entries report zero affected participants in the listed serious and other adverse-event categories, but those counts should not be generalized beyond the recorded study experience. Overall, the posted information is informative about the design and procedures while leaving the primary statistical result unavailable.

13. Why This Trial Matters Statistically

This trial raises statistical issues that are important when evaluating small crossover studies. Its enrollment was 14, and the design compared tDCS and sham within participants using two treatment sequences. In general, a crossover design can make efficient use of participant-level comparisons, but the analysis must reflect the paired structure rather than treating all observations as unrelated. The registry record does not report whether or how that structure was modeled.

The minimum 7-day separation and the two sequence orders are relevant to interpretation. In general, treatment sequence, period effects, and carryover can affect a crossover contrast. A washout interval is part of the design, but the interval alone cannot establish the absence of carryover. The record does not report analyses of these issues, so readers cannot evaluate their influence on the estimated contrast.

Another statistical point is the difference between a measured endpoint and a reported result. The registry gives a specific force measure and its intended summary format, but not the outcome values or uncertainty. A clear measurement description cannot answer whether the conditions differed or how precise any estimated difference was. The absence of posted analyses is therefore consequential: it prevents evaluation of the primary contrast and of how repeated observations were handled.

Finally, the record distinguishes neither a formal sample-size justification nor an analysis population. Planning illustrations based on an observed effect are conceptually separate from trial design justification and from observed results. For this study, the registry does not report the original design assumptions or provide the primary estimate needed to interpret an illustration tied to the observed effect. These limitations make transparent reporting of the analysis and outcome estimates especially important for readers assessing a small crossover study.

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 most important limitation of the registry record for statistical interpretation is the absence of numerical outcome results. Although the primary measure and testing procedures are described, the record does not report condition-specific means, standard errors, a treatment contrast, confidence intervals, or inferential tests. It is therefore not possible to assess the estimated effect or its precision.

The enrollment was 14, but the number contributing complete measurements to both conditions is not reported. The record does not describe withdrawals, missing measurements, exclusions, or the analysis population. This matters in a crossover comparison because paired analyses generally require information from both conditions for a participant.

The design information is also incomplete for evaluating potential biases. The registry records single masking but not who was masked, and it does not report the randomization method, allocation concealment, or counts assigned to each sequence. It describes a minimum 7-day interval but does not report analyses of period effects or carryover. A statistical analysis plan, multiplicity strategy, and formal sample-size justification are not reported in the registry record.

The brief summary describes separate strength and fatigue task groups, while the primary outcome description also refers to strength testing and an endurance task. The registry does not provide enough detail to resolve how these descriptions correspond to the enrolled participants or how each outcome was analyzed. The adverse-event counts are recorded, but detailed definitions and follow-up procedures are not reported. These gaps limit interpretation of both the outcome and safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Can Transcranial Direct Current Stimulation Improve Ambulation and Fatigue Resistance in People With MS? — NCT02987621.
• Registry record last updated 2020-07-30; status last verified 2020-07.
• Results first posted 2020-02-05.
• 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

The registry record describes NCT02987621, a completed, randomized, single-masked crossover study sponsored by Colorado State University. It enrolled 14 people with multiple sclerosis and compared tDCS with sham stimulation in two treatment sequences, with a minimum of 7 days between sessions. The primary outcome is mean leg muscle strength in Newtons, with standard error as the dispersion measure.

The record details maximal voluntary contractions and stimulation procedures, including tDCS ramped to 2 mA and sham current turned off after 30 seconds. It does not report numerical primary outcome results or inferential analyses. The adverse-event entries list zero serious and other affected participants and zero deaths in each of four condition-specific groups. The registry does not report a formal sample-size justification, missing-data methods, or the statistical analysis plan.