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 Median Nerve Stimulation Pilot (NCT04731714), a randomized na study. The primary outcome is Change in Tic Frequency From When MNS is Turned Off.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04731714 |
| Phase | NA |
| Condition | Tourette Syndrome, Tic Disorders, Tic Disorder, Chronic Motor or Vocal |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The record concerns participants in a study of Tourette syndrome and tic disorders. The primary outcome population is described as all participants in the study, with each participant contributing observations from rhythmic-stimulation blocks. Detailed eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The intervention of interest was rhythmic median nerve stimulation (MNS), a pulsed electrical stimulation approach. The study description says the investigation was intended to examine stimulation’s action on tic symptoms and gather early evidence, rather than evaluate a specific device for future use.
Comparator
Arrhythmic MNS served as the comparison condition. Participants were assigned to one of two sequences: rhythmic stimulation followed by arrhythmic stimulation, or arrhythmic stimulation followed by rhythmic stimulation. Sessions were at least a week apart.
Primary question
The primary endpoint compared mean tic frequency during on and off stimulation epochs on the rhythmic MNS day. The registry record describes an expert rater who was blind to condition and time point, and an analysis that accounted for a possible within-day carryover effect. The record does not report the estimated contrast, its confidence interval, or a significance result, so the direction and precision of the observed primary outcome cannot be assessed from this record.
3. Trial Design
This completed pilot, registered as NCT04731714, was randomized, triple-masked, and used a crossover model. Enrollment was 34. The record lists Tourette syndrome, tic disorders, and chronic motor or vocal tic disorder among the conditions. The study was sponsored by Washington University School of Medicine. Its start date was 2021-07-15, and primary completion was 2022-04-27.
Participants completed two stimulation sessions at least a week apart. The sequence was either rhythmic MNS followed by arrhythmic MNS, or arrhythmic MNS followed by rhythmic MNS. This arrangement means the comparison is within a crossover study, rather than a simple parallel-group comparison in which each participant receives only one condition. The record does not report how the random sequence was generated or whether sequence allocation was concealed.
The primary outcome was assessed on the rhythmic MNS day. The record describes four one-minute blocks for each participant, with two on and two off blocks in random order. An expert rater blind to condition and time point assessed tic frequency. The analysis compared the on and off epochs and included a factor for a possible within-day carryover effect.
The registry labels masking as triple, but the identities of the masked roles are not reported in the registry record. The study description characterizes the work as a pilot and a non-significant risk device study. It also states that the study was not intended to evaluate a specific device for future use. The eligibility criteria, detailed participant flow, and reasons for any missing observations 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.
Before assignment: 2 potential participants did not meet study inclusion criteria at screening and therefore were excluded prior to study arm assignment.
Overall Study
| Stage | Experimental: Rhythmic MNS, Then Arrhythmic MNS | Experimental: Arrhythmic MNS, Then Rhythmic MNS |
|---|---|---|
| STARTED | 16 | 16 |
| Completed Study Visit 1 | 16 | 16 |
| Completed Study Visit 2 | 16 | 16 |
| COMPLETED | 16 | 16 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants in the study, 4 blocks for each participant (2 on, 2 off, in random order)
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 | Experimental: Rhythmic MNS, Then Arrhythmic MNS | Experimental: Arrhythmic MNS, Then Rhythmic MNS | Total |
|---|---|---|---|---|
| Participants analysed | 16 | 16 | 32 | |
| Age, Continuous | years | 36.81 (SD 16.81) | 31.25 (SD 16.16) | 34.03 (SD 16.51) |
| Sex: Female, Male: Female | Participants | 4 | 7 | 11 |
| Sex: Female, Male: Male | Participants | 12 | 9 | 21 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 | 15 | 31 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 15 | 14 | 29 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 16 | 16 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Tic Frequency From When MNS is Turned Off, measured over During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Tic frequency (number of tics in 40 s) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in tic frequency in relation to turning MNS off. The operational comparison was mean tic frequency during the on versus off one-minute stimulation epochs on the rhythmic MNS day. The registry describes four blocks per participant, with two on and two off blocks in random order. Tic frequency was assessed by an expert rater blind to condition and time point.
The reported unit is the number of tics in the last 40 seconds of a block. Although the description refers to tic frequency per minute, it explains that the analysis used the last 40 seconds of each block to minimize possible carryover effects, following the approach of a cited prior study. The results were back-transformed to the number of tics in that interval. The registry identifies the reported summary as a least-squares mean with a 95% confidence interval.
This endpoint is used to quantify a short-term change in observed tic frequency across stimulation-on and stimulation-off epochs. Repeated blocks allow the comparison to draw on observations from both conditions within a participant. That structure can account for some stable differences between participants, while the analysis also included a factor for possible carryover within the day. These design features do not, by themselves, establish that the observed contrast is free of all bias or carryover.
The numerical least-squares means, contrast, and confidence interval are not reported in the registry record. Consequently, the size, direction, and precision of the primary endpoint result cannot be described from the available record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record provides an account of how the primary outcome was measured and analyzed, but it does not report the primary outcome estimate. It therefore does not establish whether mean tic frequency was higher, lower, or similar in the on and off epochs, nor does it show how precisely that comparison was estimated. A conclusion about statistical evidence for a difference cannot be drawn from the methodological description alone.
The endpoint is a count of tics over the last 40 seconds of each block, expressed as a back-transformed result. The record says a logarithmic transformation was used for tic count in the mixed models. The analysis included a factor for possible within-day carryover. These details matter because counts can be skewed and because observations taken close together may not be independent. They describe the stated analysis; they do not replace the missing estimate or uncertainty interval.
The record identifies a 95% confidence interval as the dispersion measure for the least-squares mean. General statistical context: a confidence interval communicates uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true effect lies within the reported interval, and its width is relevant to how precisely an effect has been estimated. Here, no interval endpoints are reported, so precision cannot be evaluated.
The comparison is within a crossover design, with rhythmic and arrhythmic stimulation delivered in different sessions and order randomized. This structure can help distinguish condition differences from stable participant-level differences. However, crossover interpretation depends on the adequacy of the period between sessions and on how effects from an earlier condition may persist. The record states that sessions were at least a week apart and that the primary model included a possible within-day carryover factor. It does not report an assessment of between-session carryover or a detailed rationale for the interval.
The trial’s stated purpose included replication, investigation of a hypothesized electrophysiological mechanism, assessment of the duration of effect after stimulation, and examination of individual characteristics associated with improvement. These are aims described by the investigators, not findings established by the record. The primary endpoint description is limited to tic frequency during on and off blocks on the rhythmic MNS day. Numerical results for that endpoint and the other stated aims are not reported in the registry record.
The record labels the trial a pilot and lists enrollment as 34. It does not report a sample-size justification or enough primary outcome results to assess whether the study could distinguish a meaningful effect from uncertainty. Any planning illustration based on an observed effect is not a measure of observed power, and it is not the trial’s own design justification. The posted material should be read as evidence about the stated design and analysis, not as a complete account of the strength or direction of the primary result.
9. Statistical Methods Explained
The primary analysis is described as a mixed models analysis. General statistical context: mixed models can represent repeated observations from the same participant while accounting for their correlation. This is useful when an outcome is measured in multiple blocks, because observations from one person may be more alike than observations from different people. The registry record does not provide the model formula, the full set of covariates, or details about how the repeated-measures covariance was specified.
Why use a mixed model for repeated blocks?
Each participant contributed observations from on and off blocks on the rhythmic MNS day. Treating every block as fully independent could understate the relationship among observations from the same participant. A mixed model can account for that clustering and estimate an average condition contrast while representing participant-level variation. The record says the primary population was all participants in the study, with four blocks for each participant, two on and two off, in random order. It does not state whether every participant contributed complete data to the analysis.
The sequence of on and off blocks was randomized, which helps avoid systematically placing one condition earlier or later within the session. The record also says the model included a factor for possible within-day carryover. General statistical context: a carryover term can account for the possibility that an earlier block’s stimulation may influence the outcome in a later block. Including such a term does not show that carryover was present or absent; the registry does not report its estimate or a separate test of carryover.
Why transform a count outcome?
The endpoint is tic frequency, a count outcome. The registry says the analysis used a logarithmic transformation for tic count. General statistical context: count data often have a right-skewed distribution, particularly when many observations are small and some are larger. A logarithmic transformation can make a model’s distributional assumptions more plausible and can reduce the influence of unusually large values. Whether those assumptions were adequately met cannot be determined from the registry description, because diagnostic results are not reported.
The record states that results were back-transformed to the number of tics in the last 40 seconds of stimulation blocks. General statistical context: back-transformation translates estimates from a transformed scale into a scale that is easier to interpret in the original measurement units. Because transformation changes the scale, the back-transformed estimate is not necessarily interpreted in exactly the same way as an untransformed arithmetic mean. The record labels the primary summary as a least-squares mean, but does not give the numerical estimates or explain any additional detail about how the reported summary was derived.
What does the confidence interval add?
The registry identifies a 95% confidence interval as the uncertainty measure. General statistical context: an interval places a range around an estimate to show the uncertainty associated with the fitted model and its assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that spans values representing materially different effects leaves more uncertainty about the result. No confidence interval endpoints are reported in the registry record, so neither the range nor the precision can be assessed.
The record also does not report a p-value or a conclusion about statistical significance for the primary endpoint. A significance test and a confidence interval are related ways to describe uncertainty, but neither can be reconstructed from the methodological description alone. No estimates should be inferred from the study aims or from the fact that the trial was completed.
How should the crossover structure be considered?
In a crossover study, participants experience more than one condition, and the comparison may be informed by within-participant observations. This can reduce the influence of stable differences between participants. It also makes order and time effects important: the response to a condition could depend on which condition came first, or an effect could persist into a later period. The study used two stimulation sessions at least a week apart, with the order of rhythmic and arrhythmic MNS varied between the two sequences.
The registry description of the primary model specifically mentions a possible within-day carryover effect. It does not describe a between-session carryover analysis, a period effect, or a sequence effect. Those elements are not reported in the registry record and should not be assumed to have been tested or ruled out. The record also does not state the exact timing of outcome assessments beyond the described stimulation blocks.
The trial’s masking label is triple. General statistical context: masking can reduce the influence of expectations or knowledge of assignment on participant reports, investigator behavior, or outcome assessment. The primary description identifies the expert rater as blind to condition and time point. The other masked roles and the practical success of masking are not reported in the registry record. A blindedness assessment is listed among secondary outcomes, but its results are not reported.
Overall, the stated methods identify a repeated-measures comparison, a mixed model, a logarithmic transformation, back-transformed results, and an adjustment for possible within-day carryover. These choices explain the intended analytical approach. They do not supply the missing numerical result or demonstrate that model assumptions, masking, or crossover conditions were satisfactory.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 11 outcome measures and 8 analyses. The primary endpoint is identified as change in tic frequency during the rhythmic MNS session. Secondary outcomes include change in tic severity after stimulation ends, participant and investigator CGI-I ratings, therapeutic effect and discomfort ratings using the CGI Efficacy Index, a visual analog rating of premonitory urge severity, and a blindedness assessment. The record does not report how the family of outcomes or analyses was handled statistically.
Multiplicity arises when several outcomes, time points, or analyses are examined. General statistical context: testing multiple questions can increase the chance that at least one result appears statistically significant by chance. Methods such as prespecifying a primary outcome, adjusting significance thresholds, or distinguishing confirmatory from exploratory analyses can help readers interpret a collection of results. The registry identifies a primary outcome, but a multiplicity adjustment or a broader statistical analysis plan is not reported in the registry record. The individual estimates and test results for the other outcomes are also not reported.
The primary population is described as all participants in the study, with four blocks per participant. The record does not report how missing block observations were handled, whether any imputation was used, or whether analyses excluded participants with incomplete data. A participant flow account and the reasons for missing observations are not reported in the registry record. The phrase “all participants” identifies the stated target population for the endpoint, but does not establish that all enrolled participants contributed complete observations.
The record does not report an intention-to-treat definition, a per-protocol population, sensitivity analyses, or a plan for handling protocol deviations. It also does not report the trial’s sample-size justification or interim-analysis plan. These omissions limit assessment of how prespecified the analyses were and how robust the conclusions would be to alternative handling of missing data or multiple comparisons.
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 |
|---|---|---|---|
| Experimental: Rhythmic MNS | 0 | 32 | 0.0% |
| Experimental: Arrhythmic MNS | 0 | 32 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Experimental: Rhythmic MNS | 0 of 32 |
| Experimental: Arrhythmic MNS | 0 of 32 |
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 |
|---|---|
| Experimental: Rhythmic MNS | 4 of 32 |
| Experimental: Arrhythmic MNS | 3 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Experimental: Rhythmic MNS | Experimental: Arrhythmic MNS |
|---|---|---|---|
| Nervous system disorders | 2 of 32 | 3 of 32 | |
| Headache | Nervous system disorders | 1 of 32 | 0 of 32 |
| Itch | Nervous system disorders | 1 of 32 | 0 of 32 |
The registry lists serious adverse events for rhythmic MNS and arrhythmic MNS separately. In each group, 32 participants were recorded as at risk, and no serious adverse events were recorded. Deaths were recorded as 0 for each group. The record lists 4 other adverse events for rhythmic MNS and 3 for arrhythmic MNS.
These are registry counts, not evidence by themselves that an event was caused by stimulation. The record does not give the event descriptions for the other adverse events, their timing, severity, relatedness assessments, or participant-level details. It also does not provide a narrative explaining how adverse events were collected or whether the same participant could contribute events in both crossover conditions.
General statistical context: a count of zero serious events does not prove that a risk is absent, particularly when the amount of observation is limited. The reported counts should be interpreted as events recorded under the registry’s categories and reporting practices. They do not establish comparative safety or quantify a rate of harm. The crossover design and the matching at-risk counts do not make the groups independent parallel arms. No broader safety conclusion is supported by these figures alone.
12. What the Result Does, and Does Not, Mean
The registry record documents a pilot study designed to compare rhythmic with arrhythmic median nerve stimulation and to assess tic frequency during stimulation-on and stimulation-off blocks. It gives useful detail about the crossover sequences, the repeated-block outcome, the blinded expert rating, and the mixed-model approach. It also reports the adverse-event counts in the two stimulation categories.
However, the primary endpoint’s numerical estimates and confidence interval are not reported in the registry record. Without them, the observed direction, size, and precision of the on-versus-off difference cannot be described. A claim that the primary outcome favored either condition, or that the comparison was statistically significant or not significant, would go beyond the reported information.
The investigators’ stated aims included replication of earlier findings, examination of a proposed electrophysiological mechanism, assessing how long an effect might last after stimulation, and exploring participant characteristics associated with improvement. Those aims explain why the study was conducted; they are not evidence that any of those effects or mechanisms were demonstrated. Numerical results for these questions are not reported in the registry record.
The study is identified as a pilot, and its description says it was not intended to evaluate a specific future-use device. It was intended to investigate the action of pulsed electrical stimulation on tic symptoms and gather early evidence. Consequently, the record should not be treated as a definitive evaluation of a clinical device or as a complete basis for judging the magnitude or durability of any effect.
The reported safety counts should likewise be interpreted narrowly. They record no serious adverse events and deaths of 0 in either stimulation group, alongside other adverse-event counts. They do not establish that the conditions are free of risk, nor do the counts alone establish a causal difference. Overall, the registry record is informative about design and planned measurement, but the missing outcome estimates prevent a statistical reading of the primary result.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that are especially relevant to short-term stimulation studies. The primary endpoint was measured repeatedly within participants, with on and off epochs arranged in random order. That structure makes the within-participant relationship among observations important, and the registry’s use of a mixed model reflects the need to account for repeated data rather than treating every block as unrelated.
The endpoint is a count, and the record reports use of a logarithmic transformation followed by back-transformation. This makes the distinction between the model’s analysis scale and the clinical measurement scale important for interpretation. Reporting both the method and the uncertainty around the back-transformed estimate would be needed to judge how large and precise the observed contrast was. The registry identifies a 95% confidence interval but does not provide its endpoints.
The crossover design also makes order and carryover relevant. Randomizing the order of on and off blocks and including a possible within-day carryover factor are explicit design and analysis features. At the session level, the order of rhythmic and arrhythmic stimulation varied, with sessions at least a week apart. The registry does not report an analysis of between-session carryover, so that aspect cannot be evaluated from the record.
Finally, the study had multiple outcomes and analyses, including symptom, urge, therapeutic-effect, discomfort, and masking measures. Understanding how those questions were prioritized and whether multiplicity was addressed would help distinguish the primary confirmatory question from exploratory aims. The registry identifies a primary endpoint, but does not report a multiplicity plan or numerical results. The statistical interest of this pilot lies in its repeated-measures and crossover structure; judging the evidence it produced requires outcome estimates and analysis details that are not reported in the registry record.
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 consequential limitation for interpreting the posted results is that the primary estimate and its confidence interval are not reported in the registry record. The record therefore does not permit assessment of the observed direction, magnitude, or precision of the primary comparison. It also does not report a primary-outcome p-value or a statistical conclusion.
The registry gives a brief description of the model but not its complete specification. It does not report the model formula, covariance structure, diagnostic checks, or estimates for the possible within-day carryover factor. Although the primary endpoint population is described as all participants, the handling of missing blocks and incomplete participant data is not reported. This leaves uncertainty about the analyzed observations and the influence of missing data.
The crossover structure makes period, sequence, and between-session carryover relevant considerations. The record reports the two treatment sequences and that sessions were at least a week apart, and it mentions a within-day carryover factor in the primary model. It does not report an analysis or rationale concerning between-session carryover, period effects, or sequence effects. The adequacy of the interval between sessions therefore cannot be judged from the record.
Masking is labeled triple, and the primary outcome description states that the expert rater was blind to condition and time point. The masked roles and the results of the listed blindedness assessment are not reported in the registry record. The record also lists multiple outcomes and analyses without reporting a multiplicity strategy, full statistical analysis plan, sample-size justification, or interim-analysis plan. These reporting gaps limit assessment of prespecification and robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Median Nerve Stimulation Pilot — NCT04731714.
- Registry record last updated 2023-10-05; status last verified 2023-09.
- Results first posted 2023-10-05.
- 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.
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18. Record Summary
NCT04731714 is a completed randomized, triple-masked crossover pilot sponsored by Washington University School of Medicine. Enrollment was 34. Participants were assigned to rhythmic MNS followed by arrhythmic MNS, or the reverse sequence, with sessions at least a week apart.
The primary outcome compared tic frequency during on and off epochs on the rhythmic MNS day. It was assessed by an expert rater blind to condition and time point. The described mixed model included a possible within-day carryover factor and used a logarithmic transformation for tic count; results were back-transformed to the number of tics in the last 40 seconds of blocks.
The primary estimates and confidence interval are not reported in the registry record. The record also does not report how missing observations or multiplicity were handled. Serious adverse events and deaths were recorded as 0 in both stimulation groups; other adverse events were recorded as 4 for rhythmic MNS and 3 for arrhythmic MNS.