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 BreEStim and tDCS for Neuropathic Pain Management - Healthy Subjects (NCT03302780), a randomized na study. The primary outcome is Electrical Pain Threshold (EPT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03302780 |
| Phase | NA |
| Condition | Pain Management |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The University of Texas Health Science Center, Houston |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers enrolled in the record for NCT03302780. Although the broader study description discusses neuropathic pain after spinal cord injury, amputation, or brain injury, this record covers healthy volunteers, not those patient populations.
Intervention
Active tDCS applied to the current dominant primary motor cortex (M1), followed by BreEStim delivered transcutaneously to the median nerve on the current dominant side. The registry description specifies 20 minutes of active tDCS and 20 minutes of BreEStim, with BreEStim described as 160 stimulations.
Comparator
Sham tDCS to the current dominant M1, followed by BreEStim to the median nerve on the current dominant side. The described sham tDCS and BreEStim sessions are each 20 minutes, and BreEStim is described as 160 stimulations.
Primary question
How does electrical pain threshold (EPT), a measure of the electrical current at which pricking pain is first evoked, vary from baseline to the recorded post-stimulation time points under the active-tDCS and sham-tDCS conditions? The study hypothesis is that a single combined session would have an additive analgesic effect. That is a hypothesis, not a result: the registry record does not report a numerical EPT comparison or an analysis of that hypothesis.
3. Trial Design
This completed study is registered as a randomized, single-masked crossover study of healthy volunteers. The registry lists enrollment as 6. Its two described treatment conditions pair BreEStim with either active tDCS or sham tDCS. In both conditions, tDCS is applied to the current dominant primary motor cortex (M1), then BreEStim is applied to the median nerve on the current dominant side.
The treatment descriptions specify 20 minutes of tDCS followed by 20 minutes of BreEStim. The active condition uses active tDCS; the comparator condition uses sham tDCS. The record describes BreEStim as 160 transcutaneous stimulations in each condition. Because the design is crossover, the treatment conditions are intended to be compared within participants rather than solely between separate groups. The registry does not report the order in which participants received the conditions, whether order was balanced, or any washout interval. Those details should not be inferred from the design label.
Single masking is reported, but the record does not identify which participants, investigators, or other personnel were masked. The study phase is listed as NA. The status is COMPLETED, with a start date of 2016-04-06 and a primary completion date of 2016-05-26. The sponsor is The University of Texas Health Science Center, Houston.
The broader study description refers to people with spinal cord injury, brain injury, or amputation, while also stating that those populations are covered by separate records. The healthy-volunteer record should therefore be interpreted as a study of the sensory endpoint in this population, not as evidence about pain outcomes in those patient groups.
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 and BreEStim; Then M1 tDCS and BreEstim | M1 tDCS and BreEStim; Then Sham tDCS and BreEstim |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 34 (24 to 45) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Electrical Pain Threshold (EPT), measured over baseline, 10 minutes after tDCS, 10 minutes after BreEstim.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mA |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is Electrical Pain Threshold (EPT), measured in mA. It is described as the lowest electrical current that first evokes a sensation of pricking pain. EPT is a quantitative sensory test: it turns a sensory response into a measurable threshold that can be compared across assessment times or conditions.
In general, a threshold measure can help characterize sensitivity to a standardized stimulus. Assessing EPT in healthy volunteers allows the study to examine sensory responses to the stimulation procedures without treating the measure as a clinical pain outcome in people with neuropathic pain. The record lists assessments at baseline, 10 minutes after tDCS, and 10 minutes after BreEstim. The sequence is relevant because tDCS precedes BreEStim in both arm descriptions.
The registry specifies that the outcome is summarized as a mean with standard deviation. Those summary statistics describe the center and spread of measured values, but they do not by themselves establish a treatment effect. A comparison, its uncertainty, and the analysis approach would be needed to assess how the conditions relate to EPT. The registry record does not report a reduced numerical comparison across the listed time points, so the direction and magnitude of any change cannot be determined from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies EPT as the primary outcome and lists measurements at baseline, 10 minutes after tDCS, and 10 minutes after BreEstim. It does not report numerical EPT means or standard deviations for those assessments, nor does it report an analysis comparing the active-tDCS and sham-tDCS conditions. The outcome has several time points and was not reduced to one comparison in the registry record. Consequently, the posted results do not establish whether EPT changed, whether any change differed by condition, or how precisely such a difference was estimated.
This absence of a reported comparison is not evidence that the conditions produced identical values. It also does not establish that the study hypothesis was supported. Without outcome estimates and uncertainty measures, readers cannot assess the size, direction, or precision of a treatment contrast. The registry lists no outcome analyses. No p-value or confidence interval for the primary endpoint is reported in the registry record.
In general, a mean describes the average observed measurement, while a standard deviation describes variation among measurements. Neither directly communicates the uncertainty in a comparison. A confidence interval is a range of values compatible with the data and analysis under its assumptions; its width helps show how precisely an effect is estimated. No such interval is reported for EPT here. A p-value, if reported, would address compatibility with a specified statistical null model, but would not by itself express the size or clinical importance of an effect. No primary-outcome p-value is reported.
The crossover design can support within-participant comparisons, which in general may account for stable differences between people. But interpreting a crossover comparison also depends on details such as treatment order, possible carryover, and the timing of assessments. The registry does not report order, washout, or an analysis accounting for these issues. It is therefore not possible to evaluate those design features from this record.
The enrollment entry is 6. That number gives context for the scale of the study, but it does not substitute for endpoint estimates or their uncertainty. The safety entries report no adverse events in the listed categories, but those counts do not answer the EPT question. Overall, the record describes the question and procedures, while leaving the main numerical efficacy result and its statistical precision unreported.
9. Statistical Methods Explained
Randomization and crossover address different aspects of a trial design. Randomization assigns treatment condition or sequence using a chance-based process, helping limit systematic allocation differences. A crossover design exposes participants to more than one condition, allowing comparisons within the same participant. In general, within-participant comparisons can reduce the influence of stable characteristics that differ from person to person. The registry identifies the study as randomized and crossover, but does not report the assigned sequences or the procedure used to generate them.
What does the crossover design imply?
In a crossover study, measurements from the same participant are related rather than independent. Statistical methods should account for that pairing; treating repeated observations as if they came from unrelated participants can misstate uncertainty. A crossover analysis may also need to consider period effects, treatment order, and carryover, meaning an effect of an earlier condition that remains during a later condition. These are general design considerations, not claims about what occurred in this study. Treatment order, washout timing, and methods for addressing period or carryover effects are not reported in the registry record.
The described sequence within each condition is tDCS followed by BreEStim. The EPT timeframe includes baseline, 10 minutes after tDCS, and 10 minutes after BreEstim. These repeated assessment times raise a question about which contrast is intended to answer the primary question: change from baseline, a difference between conditions at an assessment, or a pattern across time. The registry does not report a single numerical comparison or a statistical model specifying the contrast.
What do mean and standard deviation convey?
The endpoint is continuous and is summarized as a mean with standard deviation. In general, the mean gives a measure of the center of observed values. The standard deviation describes their dispersion around that center. A standard deviation is not a confidence interval and does not by itself show how precisely a treatment difference is estimated. To interpret a contrast, readers would need the relevant condition-specific estimates, the comparison, and an uncertainty measure, such as a confidence interval. Those primary-outcome analysis results are not reported in the registry record.
How should significance tests and intervals be read?
In general, a p-value evaluates how unusual data would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. A confidence interval communicates uncertainty around an estimate and may show which effect sizes remain compatible with the data under the analysis assumptions. Neither a p-value nor a confidence interval for the primary EPT comparison is reported in this record. No conclusion about statistical significance or precision can therefore be drawn from the posted outcome information.
The registry includes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are described as planning illustrations based on an observed effect, not as the trial's own design. They should not be read as observed power. The registry record does not report a sample-size justification for the trial or the numerical planning results in the information. No new sample-size calculation can be inferred from the design details alone.
Why does dispersion matter?
In general, greater variation among measurements makes an average difference harder to estimate precisely. Standard statistical methods often rely on assumptions about the distribution and variability of observations. If data are more variable than a model allows, uncertainty can be understated. In count outcomes, over-dispersion means variability exceeds what a basic count model expects; that concept is not directly the issue for this continuous EPT endpoint, but illustrates why a model's assumptions should fit the data. The registry does not report diagnostics or detailed modeling choices for EPT.
Randomization, masking, and the measurement definition describe important parts of the study, but they do not supply the missing numerical outcome analysis. The analysis population, missing-data approach, handling of repeated observations, and any adjustment for multiple comparisons are not reported in the registry record. Those omissions limit independent assessment of the inferential methods.
10. Multiplicity, Missing Data and Analysis Populations
The primary EPT outcome is listed at baseline, 10 minutes after tDCS, and 10 minutes after BreEstim. Comparing multiple assessments or contrasts can create a multiplicity issue: in general, the more inferential tests conducted, the greater the chance of finding a nominally notable result by chance if no adjustment or prespecified testing strategy is used. The registry does not report a multiplicity strategy, a hierarchy of comparisons, or which time-point contrast was designated for the primary inference.
The registry lists 2 outcome measures and 0 analyses. It identifies EPT as primary, but does not provide a numerical result for it. No analysis population is defined in the record, and the handling of missing outcome values is not reported in the registry record. The record also does not describe whether all enrolled participants contributed measurements at each listed time point, or how incomplete crossover observations would be handled.
In general, missing-data methods can affect estimates when the chance of missingness is related to observed or unobserved outcomes. A complete-case analysis, imputation, or model-based approach each relies on assumptions; the appropriate interpretation depends on what was planned and what data were available. None of those choices should be presumed for this study. Interim analyses, protocol deviations, and analysis-set definitions are also not reported in the registry record. With no documented analysis strategy or endpoint estimates, the strength and robustness of any treatment comparison cannot be evaluated from the posted results.
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 |
|---|---|---|---|
| Sham tDCS and BreEStim | 0 | 6 | 0.0% |
| Active tDCS (M1) and BreEStim | 0 | 6 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sham tDCS and BreEStim | 0 of 6 |
| Active tDCS (M1) and BreEStim | 0 of 6 |
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 |
|---|---|
| Sham tDCS and BreEStim | 0 of 6 |
| Active tDCS (M1) and BreEStim | 0 of 6 |
The registry lists serious adverse events, other adverse events, and deaths separately for the sham-tDCS-and-BreEStim condition and the active-tDCS-and-BreEStim condition. For each condition, 6 participants are listed as at risk. The recorded counts are 0 serious adverse events, 0 other adverse events, and 0 deaths in each condition. No serious adverse event terms are listed.
These entries are counts within the registry's stated at-risk groups. They are not an estimate of comparative safety, and a zero count does not show that an event is impossible or that the intervention is free of risk. In general, the ability to detect uncommon events depends on the amount and duration of observation, as well as how events are defined and collected. The registry record does not provide further detail about adverse-event collection, observation duration, or specific event definitions.
Because the study is crossover, the same people may contribute exposure to more than one condition; the registry's at-risk entries should not be added to infer a count of distinct participants. The adverse-event figures describe what is recorded for each condition, not a statistical comparison of safety between them. They do not provide information about EPT or the hypothesized analgesic effect.
12. What the Result Does, and Does Not, Mean
The record describes a randomized crossover study in healthy volunteers comparing BreEStim paired with active tDCS against BreEStim paired with sham tDCS. Its primary endpoint is EPT, with assessments listed at baseline, 10 minutes after tDCS, and 10 minutes after BreEstim. This establishes the measurement and treatment question addressed by the study record.
The registry record does not report the numerical EPT results or an analysis comparing conditions. It therefore does not show the direction or magnitude of any difference, whether there was a change from baseline, or the precision of a comparison. The stated hypothesis about an additive analgesic effect should not be confused with a finding. The available record cannot establish that the hypothesis was supported or refuted.
The results also should not be generalized to patients with neuropathic pain after spinal cord injury, brain injury, or amputation. The record explicitly covers healthy volunteers, while those other populations are addressed by separate records. EPT is a sensory threshold measure; it is not itself a report of clinical pain relief in those patient populations.
The safety counts are limited to the adverse-event entries in the registry. They report zero events in each listed category for each condition, but do not prove absence of risk. The enrollment entry and the absence of a posted outcome analysis further constrain what can be learned from this record. In general, a treatment conclusion requires interpretable outcome estimates, uncertainty, and sufficient detail about the analysis. Those elements are not available for the primary endpoint in the registry record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how design and reporting determine what can be concluded. A randomized crossover design can be useful when an outcome is measured under more than one condition in the same participants. In general, this design can make within-person comparisons more informative by controlling for stable individual differences. It also requires attention to treatment order, period effects, and possible carryover, which are not described in the registry record.
The outcome is a quantitative sensory threshold measured at several time points. That creates a need to distinguish the planned primary contrast from other possible time-point comparisons and to account for repeated observations. Without the numerical estimates and analysis details, the design description alone cannot answer whether the intervention conditions differed or how precisely any difference was estimated.
The record also illustrates why a hypothesis and an outcome result are not interchangeable. The stated expectation of an additive analgesic effect identifies the scientific motivation, but it does not establish that an effect was observed. Likewise, the adverse-event entries address safety reporting and do not substitute for the primary EPT analysis.
Finally, the population boundary matters. This record concerns healthy volunteers, while the broader clinical motivation refers to neuropathic pain in other populations that are covered separately. Clear interpretation requires keeping the population, sensory endpoint, treatment comparison, and missing analysis results distinct. The registry's limited reporting makes these distinctions especially important.
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 principal limitation for interpretation is that the registry record does not report numerical EPT results or a statistical comparison. Although it identifies the outcome, measurement unit, summary type, and assessment times, it does not provide estimates from which to judge direction, magnitude, or precision. The record also lists 0 analyses.
The registry describes a crossover design but does not report treatment order, washout timing, or methods for addressing period and carryover effects. It identifies the study as single-masked without specifying who was masked. The analysis population, handling of missing measurements, and approach to repeated observations are not reported in the registry record. The record also does not describe a multiplicity strategy for the several listed assessment times.
The study population is healthy volunteers. Results from this record, even if numerical results were available, would not directly answer whether the intervention changes clinical neuropathic pain in people with spinal cord injury, brain injury, or amputation. Those populations are addressed by separate records according to the study description.
The enrollment entry is 6, and the record contains no primary-outcome analysis with which to assess statistical precision. The reported zero adverse-event counts should also be interpreted narrowly: they are registry counts for the listed categories, not proof that adverse events cannot occur. Further details about event collection and observation are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BreEStim and tDCS for Neuropathic Pain Management - Healthy Subjects — NCT03302780.
- Registry record last updated 2021-04-27; status last verified 2021-04.
- Results first posted 2020-12-03.
- 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
NCT03302780 is a completed randomized, single-masked crossover study in healthy volunteers, sponsored by The University of Texas Health Science Center, Houston. It compares BreEStim paired with active tDCS to BreEStim paired with sham tDCS. The primary outcome is EPT in mA, assessed at baseline, 10 minutes after tDCS, and 10 minutes after BreEstim.
The registry lists enrollment as 6 and reports 0 serious adverse events, 0 other adverse events, and 0 deaths in each condition. It does not report a numerical EPT comparison or an analysis of the primary outcome. The treatment hypothesis is therefore not a reported finding, and the effect and its precision cannot be assessed from the posted results.