This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Transcranial Direct Current Stimulation to Lower Neuropathic Pain in People With Multiple Sclerosis (NCT03219073), a randomized na study. The primary outcome is Cerebral Glucose Uptake in Patients With Multiple Sclerosis With Neuropathic Pain.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03219073 |
| Phase | NA |
| Condition | Multiple Sclerosis, Neuropathic Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Thorsten Rudroff |
| Results posted | Yes |
2. Clinical Question
Population
People with multiple sclerosis and neuropathic pain were the intended population. The primary outcome description says the study concerned people with multiple sclerosis who received brain stimulation or sham stimulation. The primary population description also states that the pilot study had only one subject with active transcranial direct current stimulation. The registry record reports enrollment of 1 overall, so it does not describe a study population large enough to characterize variation in outcomes.
Intervention
Active transcranial direct current stimulation was delivered through sponge surface electrodes. The anodal electrode was placed over the motor cortex contralateral to the participant’s worst somatic pain area. The study aimed to examine changes in brain activity following stimulation, with neuropathic pain outcomes also listed as secondary measures.
Comparator
The comparator was sham stimulation using the same device. The registry description says the electrodes were placed in the same positions as for active stimulation, but the stimulator was turned off after 90 seconds. The description notes that participants felt the initial itching sensation but received no current for the rest of the sham procedure.
Primary question
The primary question was whether active stimulation was associated with a change in whole or regional cerebral glucose uptake, assessed using positron emission tomography with a glucose analogue tracer. The primary outcome was defined as mean standardized uptake value, with a timeframe of 1 week. The registry record contains no posted primary outcome values or comparison between active and sham groups, so it cannot answer whether uptake differed between them.
3. Trial Design
The registry describes a randomized, double-masked, parallel-group study comparing active transcranial direct current stimulation with sham stimulation. The listed phase is NA. A randomized design ordinarily assigns participants to intervention groups by chance, while a parallel design keeps each participant in an assigned group rather than crossing participants between conditions. These are general definitions; the record does not describe the sequence-generation method, allocation concealment, or the roles covered by double masking.
The active intervention used a tDCS device to deliver direct current through two sponge surface electrodes. The anodal electrode was placed over the motor cortex contralateral to the worst somatic pain area. The sham procedure used the same electrode positions, with the stimulator turned off after 90 seconds; the registry description says the initial itching sensation was felt but no current was received for the remainder. Further details about treatment frequency, session duration, or adherence are not reported in the registry record.
Enrollment was 1, and the primary outcome description specifies that the pilot study had one subject with active stimulation. The record therefore does not provide an evaluable active-versus-sham primary outcome comparison. The study status is terminated. Its listed start date is 2018-02-01 and its primary completion date is 2018-06-16; the reason for termination is not reported in the registry record. The sponsor is Thorsten Rudroff. The dates and status describe the registry entry and do not explain why recruitment ended or whether any planned procedures were completed.
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
| Stage | SHAM tDCS | Active tDCS With a tDCS Device |
|---|---|---|
| STARTED | 0 | 1 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: For this pilot study we only had one subject with active transcranial direct current stimulation.
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: For this pilot study we only had one subject who received Active tDCS.
| Characteristic | Unit | Active tDCS With a tDCS Device |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | Years | 64 (SD 0) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Cerebral Glucose Uptake in Patients With Multiple Sclerosis With Neuropathic Pain, measured over 1 week.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of glucose uptake increase |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was cerebral glucose uptake in people with multiple sclerosis with neuropathic pain. The registry description identifies whole and regional brain glucose uptake measured using positron emission tomography with a glucose analogue tracer. The outcome variable is described as the mean standardized uptake value, and the unit is given as percentage of glucose uptake increase. The stated timeframe is 1 week.
Glucose uptake was chosen to assess brain activity and explore a possible mechanism of transcranial direct current stimulation. In general, a mechanistic endpoint is intended to characterize a biological process that may relate to an intervention, rather than directly measure a participant’s symptoms or daily functioning. This distinction matters: an imaging measure can address a question about brain activity, but by itself it does not establish whether pain changed or whether a change was important to participants.
The registry also lists change in neuropathic pain on a visual analog scale and change in the Neuropathic Symptom Inventory as secondary outcomes. It does not report values for these outcomes, the scoring details, or a primary-versus-secondary analysis plan. No numerical glucose uptake result, variability estimate, or comparison between groups is reported in the registry record. The endpoint description therefore explains what the study intended to measure, but not what effect was observed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is the scale of the completed study as recorded: enrollment was 1, and the primary outcome description says there was one subject receiving active stimulation. The study was terminated, and the registry record lists no analyses. It consequently does not provide a group comparison for cerebral glucose uptake or an estimate of the difference between active and sham stimulation. No primary outcome mean, standard deviation, confidence interval, or test result is reported in the registry record.
Without a comparative estimate, the record cannot establish the direction or magnitude of a treatment contrast. A single participant’s measurement, even if available, would not show how outcomes vary across participants or permit a reliable estimate of between-group uncertainty. The registry record does not report that participant’s primary outcome value in any case. The listing of an intended endpoint and a planned comparison should not be read as evidence that the comparison was completed or produced a result.
Randomization and masking describe design features, not findings. Random allocation can help make comparison groups similar on average when enough participants are enrolled and analyzed. Masking can reduce the influence of expectations on treatment delivery or outcome assessment, depending on who is masked. Those general benefits cannot substitute for outcome data. With enrollment of 1, the record offers no basis for evaluating whether allocation produced comparable groups, whether masking was maintained, or whether group outcomes differed.
The registry lists neuropathic pain on a visual analog scale and the Neuropathic Symptom Inventory as secondary outcomes, but reports no results for either. It also does not report confidence intervals or other measures of precision. A confidence interval, in general, describes a range of values compatible with the data and analysis under its assumptions; without a reported estimate and its uncertainty, precision cannot be assessed.
Thus, the posted record is informative about the study’s intended mechanistic question, intervention descriptions, and limited enrollment, but not about an observed effect. Its termination reason, detailed analysis plan, and explanation for the low enrollment are not reported in the registry record. Any sample-size planning values displayed with the posted material should be understood as planning illustrations, not as observed power or evidence that the trial tested its question adequately.
9. Statistical Methods Explained
The registry identifies the primary outcome as a continuous measure summarized by a mean, with standard deviation as the stated dispersion. These choices describe how a numeric outcome could be reported: the mean indicates a central value, while the standard deviation describes variability among individual measurements. They answer different questions. The standard deviation is not the uncertainty in the estimated mean, and neither quantity is available as a primary result in the registry record.
What a mean and standard deviation would describe
In general, a mean combines measured values into a single central summary. A standard deviation indicates how spread out those values are around that summary. When observations are scarce, both summaries are difficult to interpret as descriptions of a broader population: an individual value may not represent typical variation, and there may be too little information to estimate that variation. Here, the record gives enrollment of 1 and no outcome values, so no mean or standard deviation can be evaluated from the posted results.
A confidence interval is a general way to express the statistical uncertainty around an estimate. It depends on the estimated effect, the observed variability, the analysis method, and the amount of information in the data. A narrow interval would indicate greater precision under the method’s assumptions; a wide interval would indicate less. No confidence interval for the primary outcome is reported in the registry record. It would be inappropriate to infer precision from the study’s randomized or masked labels alone.
What a group comparison requires
An active-versus-sham contrast requires outcome information from both groups, along with a defined analysis. Randomization ordinarily supports a causal comparison by assigning participants to groups by chance, but it does not create observations or guarantee balance in a very small study. With enrollment of 1 and a primary outcome description specifying one active participant, the record does not supply an analyzable comparison between groups. The registry also lists zero analyses. A treatment effect, standard error, confidence interval, or p-value is therefore not reported in the registry record.
The record’s statistical planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It is described as based on the observed effect and as considering a stated fraction of that effect. These are assumptions for an illustration, not evidence about the study’s actual design justification. The registry record does not report a sample-size justification for the trial, and planning calculations are not observed power. The record does not report a usable observed effect estimate from which to assess the illustration.
Why variability and distribution matter
General statistical methods rely on assumptions about the outcome and its sampling distribution. A normal approximation can be useful when its assumptions are reasonable, but it may not represent the data well when observations are extremely limited or the outcome distribution is unusual. Over-dispersion is a general concern when observed variability exceeds what a model assumes; it can make model-based uncertainty too small if ignored. The registry does not report a distributional assessment or an over-dispersion analysis. With no primary outcome values or analysis, these issues cannot be checked for this study.
The imaging endpoint is described as mean standardized uptake value, while its unit is stated as percentage of glucose uptake increase. Interpretation would require clarity about the precise calculation, baseline or reference measurement, and any regional analysis definitions. Those details, as well as the analysis population and handling of missing imaging measurements, are not reported in the registry record. The endpoint description alone does not establish how a numerical result would have been derived.
Likewise, a p-value, if reported, would address compatibility between data and a specified null model under the analysis assumptions; it would not measure the size or practical importance of an effect. No p-value is reported. The key statistical limitation is therefore not a borderline finding or an imprecise estimate that can be quantified from the registry entry. It is the absence of a reported primary outcome analysis and the lack of a completed group comparison in the recorded enrollment.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary imaging outcome and two secondary outcomes: change in neuropathic pain on a visual analog scale and change in the Neuropathic Symptom Inventory. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase. General approaches to this issue include identifying a primary outcome in advance, adjusting inference across tests, or clearly labeling secondary analyses as exploratory. The registry record does not report a multiplicity adjustment or a detailed plan for managing multiple outcomes.
The record lists three outcome measures and zero analyses. It does not report which outcome assessments were completed, how many tests or regions were intended for the imaging endpoint, or whether any interim analyses were planned. These details are not reported in the registry record. No claim about selective reporting or interim monitoring can be made from the listing alone.
Missing-data handling is also not reported in the registry record. There is no description of an analysis population, such as whether analysis was intended to follow randomized assignment, nor a method for handling absent scans, incomplete questionnaires, or withdrawals. With enrollment of 1 and no posted outcome analysis, it is not possible to determine whether missing data affected the findings or whether all intended measurements were obtained.
These omissions limit reproducibility and interpretation, but they do not imply that any particular analysis method was used. The registry record does not report the statistical analysis plan, outcome-specific analysis populations, imputation methods, or rules for excluding measurements. No adjustment or missing-data procedure should be inferred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Active tDCS With a tDCS Device | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Active tDCS With a tDCS Device | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Active tDCS With a tDCS Device | 0 of 1 |
The adverse-event listing records 1 participant at risk in the active stimulation group. It reports 0 serious adverse events, 0 other adverse events, and 0 deaths. No serious adverse-event terms are listed. These are counts recorded for the enrolled group, not estimates of the frequency of adverse events in a broader population.
With only 1 participant at risk, the absence of a recorded event cannot rule out events that might occur in a larger group or with different exposure. It also does not establish that no event could occur; it indicates only that the registry record lists none for this participant and group. The record does not provide comparable adverse-event counts for a sham group, and enrollment of 1 does not allow a meaningful safety comparison between groups.
The record does not report details about how adverse events were collected, their observation period, severity grading beyond the serious-versus-other categories, or whether events were judged related to stimulation. Those details are not reported in the registry record. The event counts should therefore be read narrowly as the posted counts, rather than as a comprehensive safety assessment.
12. What the Result Does, and Does Not, Mean
The study’s stated scientific aim was to examine whether transcranial direct current stimulation changes whole or regional brain activity in people with multiple sclerosis and neuropathic pain. The proposed imaging measure was cerebral glucose uptake assessed by positron emission tomography. Neuropathic pain and symptom inventory changes were also listed as secondary outcomes. This mechanistic focus is distinct from a direct test of symptom improvement: the imaging endpoint concerns brain activity, while the secondary measures concern reported pain or symptoms.
The record does not report numerical results for the imaging endpoint or secondary outcomes. It therefore does not show whether glucose uptake changed, whether active and sham groups differed, or whether pain measures changed. It also does not provide estimates of effect size or precision. The title and objectives describe the question the investigators set out to study, not a demonstrated result.
The registry reports enrollment of 1, specifies one active participant in the primary outcome description, and gives the study status as terminated. No primary outcome analyses are listed. The termination reason is not reported in the registry record. These registry entries explain why the posted entry cannot support a reliable comparative conclusion, but they do not reveal whether the study ended because of recruitment, feasibility, funding, or another reason.
In general, a pilot study may be intended to explore feasibility or generate hypotheses rather than provide a definitive estimate. The record identifies this as a pilot study, but does not report a formal feasibility objective or decision criteria. Its limited enrollment means that the central mechanistic and clinical questions remain unanswered by the posted results. No conclusion about benefit, lack of benefit, or safety in a wider population follows from the absence of a reported analysis.
13. Why This Trial Matters Statistically
This record illustrates the difference between a registered research question and an answered research question. It describes a randomized, double-masked, parallel comparison and a biologically focused endpoint, but reports enrollment of 1, a terminated status, and zero analyses. The design labels and detailed intervention descriptions are useful context; they do not replace outcome data.
For biostatistical interpretation, the small recorded enrollment is not merely a caveat attached to an otherwise available estimate. The primary outcome comparison itself is absent. There is no reported group contrast whose magnitude or uncertainty can be judged. This is different from a completed trial with a nonsignificant result or a wide confidence interval: neither a null result nor a quantified imprecise result is reported in the registry record.
The example also shows why statistical planning illustrations must be kept separate from evidence. Planning assumptions can describe what a hypothetical future comparison might require under specified conditions, but they do not demonstrate that a trial had adequate power or that a treatment effect was observed. The registry describes an illustration based on an observed effect, but provides no numerical primary outcome result for evaluating such an effect.
Finally, mechanistic measurements and symptom outcomes answer different questions. An imaging endpoint can be informative about a proposed biological process, while pain scales address participants’ reported symptoms. A study would need outcome data and a clear analysis to connect these kinds of measures. In this record, the distinction is clear in the listed objectives, but the results needed to evaluate either question are not reported.
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 dominant limitation is enrollment of 1, together with the primary outcome description that identifies one active-stimulation subject. The registry reports no analyses, so there is no posted active-versus-sham estimate for the primary endpoint. Without a reported outcome value and comparison group result, the effect’s direction, magnitude, and precision cannot be assessed.
The study status is terminated, but the reason for termination is not reported in the registry record. Recruitment details, the number assigned to each group, treatment completion, and whether the sham procedure was delivered are also not reported in the registry record. The entry describes a sham intervention, but the enrollment and outcome information do not establish that a participant received it.
The primary endpoint description identifies mean standardized uptake value and a unit of percentage of glucose uptake increase, but operational details of the calculation and regional analyses are not reported in the registry record. Nor are baseline measurements, outcome values, or a statistical model. These missing details prevent an independent assessment of how the imaging contrast was defined or estimated.
The registry lists secondary pain and symptom outcomes, but supplies no results, scoring details, analysis populations, or missing-data procedures. It also does not report a detailed statistical analysis plan, multiplicity approach, or interim-analysis plan. The record does not state who was masked, how masking was maintained, or whether it was assessed. These are reporting limitations; they do not establish that a particular procedure was absent from the conduct of the study.
Finally, the adverse-event counts come from the single participant recorded at risk in the active group and do not provide a comparative safety assessment. No adverse-event collection window or attribution method is reported in the registry record. These constraints make the entry useful for describing the intended study and its limited recorded enrollment, but not for estimating efficacy or characterizing safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Transcranial Direct Current Stimulation to Lower Neuropathic Pain in People With Multiple Sclerosis — NCT03219073.
- Registry record last updated 2022-11-29; status last verified 2022-11.
- Results first posted 2022-11-29.
- 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.
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18. Record Summary
NCT03219073 is a randomized, double-masked, parallel study of active versus sham transcranial direct current stimulation for people with multiple sclerosis and neuropathic pain. Its primary outcome was cerebral glucose uptake measured by positron emission tomography, with a stated timeframe of 1 week. Pain on a visual analog scale and the Neuropathic Symptom Inventory were listed as secondary outcomes.
The registry lists enrollment of 1, status terminated, and zero analyses. The primary outcome description specifies one active-stimulation subject. No primary or secondary outcome results are reported in the registry record, and the reason for termination is not reported. The adverse-event listing records 0 serious events, 0 other events, and 0 deaths among 1 active-group participant at risk. These counts do not establish comparative safety or provide a dependable estimate for a larger population.