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 HDtDCS in Logopenic Variant PPA: Effects on Language and Neural Mechanisms (NCT03805659), a randomized na study. The primary outcome is Determine Changes in Language Performance After Stimulation Sessions.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03805659 |
| Phase | NA |
| Condition | Primary Progressive Aphasia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Medical College of Wisconsin |
| Results posted | Yes |
2. Clinical Question
Population
People with primary progressive aphasia, with the study focused on logopenic variant primary progressive aphasia (lvPPA). The registry lists an enrollment of 6. It does not report the number of participants who completed each period or contributed outcome data.
Intervention
High-definition transcranial direct current stimulation (HD-tDCS) directed to the left posterior temporo-parietal cortex. The listed description specifies sessions lasting 20 minutes, with an electric current intensity of up to 2mA, delivered once a day for 10 sessions over 2 weeks.
Comparator
Sham stimulation, described as sessions with no electric current. Participants were assigned to one of two sequences: HD-tDCS followed by Sham, or Sham followed by HD-tDCS. One sequence description specifies a washout period of 16 weeks before the later HD-tDCS period.
Primary question
Whether language performance changes after stimulation sessions, as assessed before and after the intervention periods. The registry identifies this as the primary outcome but states that no data were collected for it. Consequently, the record does not provide an estimate of the difference between HD-tDCS and Sham.
The clinical question concerns a language measure rather than a direct clinical diagnosis or a brain-imaging result. The study description also mentions brain imaging, language assessment, language training sessions, and both HD-tDCS and placebo therapy sessions. The registry does not provide a detailed account of how language training was incorporated into each sequence or how changes in language performance were quantified.
The planned crossover arrangement is intended to expose participants to both stimulation conditions in different periods. This lets a comparison potentially use measurements from the same person under each condition. However, the registry record does not report outcome values, participant-level paired comparisons, or an analysis accounting for period and sequence. The stated clinical question therefore remains unanswered by the posted primary-outcome results.
3. Trial Design
This was a randomized, quadruple-masked, crossover study listed as completed. The registry lists an enrollment of 6 and identifies the condition as primary progressive aphasia. The sponsor is the Medical College of Wisconsin. The record gives a start date of 2020-02-24 and a primary completion date of 2022-05-18. The study phase is listed as not applicable.
In a crossover design, participants receive more than one study condition in sequence. Here, the two conditions were HD-tDCS and Sham, and the listed sequences were HD-tDCS followed by Sham and Sham followed by HD-tDCS. Random allocation to sequence can help balance systematic differences in treatment order. It does not, by itself, resolve possible carryover from one period to another or changes over time.
The HD-tDCS description specifies stimulation of the left posterior temporo-parietal cortex for 20 minutes, at an electric current intensity of up to 2mA, once a day for 10 sessions over 2 weeks. Sham is described as no electric current, with sessions once a day for 10 sessions over 2 weeks. The Sham-then-HD-tDCS sequence description specifies a washout period of 16 weeks before HD-tDCS. The full timing and conduct of both sequences are not reported in the registry record.
Quadruple masking indicates that the registry classified the study as masking four roles, but the identities of those roles and the procedures used to preserve masking are not reported in the registry record. The record also does not report how randomization was generated or concealed. These details matter when evaluating whether participants, staff, and outcome assessors could have anticipated or recognized a condition.
Although the study is marked completed, completion does not mean that all planned outcomes were collected or that an analysis was reported. For the primary language outcome, the record explicitly states that no data were collected. The registry does not report period-specific participant counts, withdrawal information, or reasons for missing outcome data.
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: 5 of 6 subjects were randomized. 1 subject withdrew themselves prior to starting baseline procedures.
Overall Study
| Stage | HD-tDCS, Then Sham | Sham, Then HD-tDCS |
|---|---|---|
| STARTED | 2 | 3 |
| First Intervention (2 Weeks) | 2 | 2 |
| Assessment 1 Cognitive Testing (8 Weeks After First Intervention) | 2 | 2 |
| Washout (16 Weeks) | 2 | 2 |
| Second Intervention (2 Weeks) | 2 | 2 |
| Assessment 2 Cognitive Testing (8 Weeks After Intervention) | 2 | 2 |
| COMPLETED | 2 | 2 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | HD-tDCS, Then Sham | Sham, Then HD-tDCS |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: No data were collected for this outcome measure.
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 | HD-tDCS, Then Sham | Sham, Then HD-tDCS | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 3 | 5 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 1 | 2 |
| Age, Categorical: >=65 years | Participants | 1 | 2 | 3 |
| Age, Continuous | years | 70.0 (SD 8.49) | 66.3 (SD 3.06) | 67.8 (SD 5.17) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 3 | 5 |
| 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 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 3 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 2 | 3 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Determine Changes in Language Performance After Stimulation Sessions, measured over Language performance was assessed before and after 2-week intervention and during washout periods.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in language performance after stimulation sessions. The registry describes assessment at baseline and after the stimulation procedure; its timeframe also refers to assessment before and after a 2-week intervention and during washout periods. It does not identify a specific language test, scoring scale, summary measure, or direction of improvement.
Language performance is relevant to the study question because the intervention is being evaluated in people with lvPPA, a condition involving language deficits. A measured outcome can translate a broad question about language into an observable quantity that can be compared across conditions and time points. Repeated assessment around an intervention period may also help distinguish the participant’s starting performance from later performance.
For a crossover study, interpretation depends on knowing how the outcome was scored and how measurements from each period were compared. A comparison could account for measurements from the same participant, as well as the order and timing of the conditions. The registry record does not report the scoring details or the analysis approach, so it is not possible to determine how those features would have been handled.
Most importantly, the registry states that no data were collected for this outcome measure. There is therefore no posted primary-endpoint estimate, no measure of its uncertainty, and no result showing the direction or size of any change. The endpoint’s stated purpose can be described, but its observed result cannot be interpreted from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry reports no data for the primary language-performance outcome. There is no posted comparison of HD-tDCS with Sham, no estimate of change within either condition, and no uncertainty interval or significance test for the primary question. The record therefore does not establish whether the conditions differed in language performance or how precisely any difference might have been estimated.
The study is marked completed, and the registry lists enrollment of 6. Those details describe the status and registered enrollment, not the number of participants included in a particular outcome analysis. The primary outcome explicitly has no collected data, and participant counts for completion of the crossover periods are not reported in the registry record. The enrollment figure should not be treated as the analysis sample for an unreported outcome.
The adverse-event summaries do contain group counts, but they answer a different question from the language endpoint. They describe reported serious and other adverse events among participants listed at risk in each condition. They do not provide evidence about language benefit, and they should not be substituted for the primary efficacy outcome.
A crossover design can be statistically useful because each participant may contribute observations under both conditions. That potential advantage depends on complete measurements in both periods and an appropriate analysis that respects the pairing. It also depends on whether the outcome from one period could influence the next. The registry record does not report the participant-level outcome data or the analysis details needed to assess these issues.
The listed washout period in one sequence is 16 weeks. A washout is generally intended to reduce the influence of an earlier condition on a later period. Its presence in a design description does not demonstrate that carryover was absent, and the registry record does not report a carryover assessment. The record also does not state whether period effects or treatment-by-period patterns were evaluated.
No inferential analyses are reported for the registered outcomes. Without an estimate and its uncertainty, readers cannot assess whether the available information would distinguish a meaningful condition difference from ordinary sampling variation. Even a small estimated difference would need to be read alongside its precision and the measurement’s clinical meaning; neither is available for the primary outcome.
Accordingly, the defensible reading is limited: this completed randomized crossover study was registered to assess language performance after HD-tDCS and Sham, but the record reports no primary-outcome data. This absence is not evidence that the conditions were equivalent, and it is not evidence that either condition improved language performance. It means the posted registry results do not answer the primary statistical question.
9. Statistical Methods Explained
The design combines randomization, masking, and crossover treatment periods. Each feature addresses a different source of bias, and none guarantees an unbiased or precise result on its own. Randomization assigns participants to an order of conditions. Masking is intended to limit the influence of expectations or knowledge of assignment. Crossover treatment gives a participant experience under both conditions, which can permit a within-participant comparison when the outcome is measured in each period.
Why does a crossover design need period-aware analysis?
Measurements from the same person are usually related: a participant’s performance in one period may resemble that participant’s performance in another period more closely than it resembles another person’s performance. A paired analysis uses that relationship rather than treating all observations as independent. In general, this can improve efficiency when the outcome is available for both conditions and the within-person comparison is appropriate. The registry record does not report whether paired measurements were collected for the primary outcome, and it states that no data were collected for that outcome.
In crossover studies, treatment condition is not the only possible source of change. Performance may differ between periods because of time, repeated testing, training, or the sequence in which conditions occur. A treatment effect can therefore be difficult to separate from a period effect if the analysis does not account for design structure. The registry record does not report a statistical model, a period-effect assessment, or a sequence-effect assessment.
What is carryover, and why does washout matter?
Carryover occurs when effects of an earlier condition persist into a later period. A washout interval is intended to give those effects time to diminish before the next condition begins. The Sham-then-HD-tDCS sequence description specifies a washout period of 16 weeks. The record does not report whether the interval was the same for both sequences, whether participants’ outcomes were assessed during it, or whether carryover was tested. A stated washout interval is a design feature, not proof that carryover was absent.
What would an estimate and confidence interval contribute?
In general, an effect estimate expresses the size and direction of a contrast, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval. Statistical significance alone, when reported, does not explain the size or clinical importance of an effect. The registry record reports no primary-outcome estimate or confidence interval, so neither magnitude nor precision can be evaluated.
A p-value, in general, measures how incompatible the observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. No primary-outcome p-value is reported. Because the primary data themselves are reported as not collected, a recalculated comparison from summary statistics is not available.
Why can small samples make estimates uncertain?
With few participants, each observation can have substantial influence on an estimate, and estimates may vary considerably across repeated samples. This is a general statistical concern, not a claim about the size or direction of any effect in this trial. The registry lists an enrollment of 6, but that figure does not establish how many participants completed each period or contributed to any particular analysis. In this record, the lack of primary-outcome data is more fundamental than the question of precision: there is no posted primary estimate to assess.
Over-dispersion is a general issue for count outcomes when observed variability exceeds what a simple count model expects. If relevant, it can make standard errors and confidence intervals too small when ignored. The registry does not report a primary count outcome or model, so there is no basis for asserting that over-dispersion affected this study. More generally, choosing a model requires knowing the outcome’s scale, distribution, and repeated-measure structure; those details are not reported for the primary language measure.
How should multiplicity be understood?
Multiplicity arises when several outcomes, time points, or comparisons are tested. Repeated testing can increase the chance of at least one apparently unusual result, even when there is no underlying condition difference. Statistical plans may address this with a prespecified primary contrast, adjustment procedures, or a clear hierarchy of tests. The registry identifies a primary language outcome and lists secondary outcomes concerning resting-state language-network functional connectivity and neuronal frequency distribution and connectivity measures assessed by MEG. It does not report a multiplicity strategy or analysis results for these outcomes.
Planning calculations, when used, answer a design question under assumptions; they do not describe observed outcomes. A sample-size illustration based on an observed effect is not observed power and cannot replace an estimate with uncertainty. The registry record does not report the trial’s own sample-size justification. It also does not provide primary outcome data from which a trial-specific effect estimate could be assessed.
Overall, the design terms identify a randomized, masked, crossover comparison, but the registry does not report the statistical analysis plan, outcome data, or inferential results for the primary endpoint. General explanations of paired analysis, confidence intervals, carryover, and multiplicity describe issues relevant to this design; they cannot supply the missing trial-specific analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome concerning language performance and lists secondary outcomes concerning left temporo-parietal cortex functional connectivity and MEG measures. Having several outcomes or repeated measurements can create multiplicity: the more comparisons examined, the greater the chance that an apparently notable finding arises by chance. A prespecified testing hierarchy or adjustment can help control that risk. The registry record does not report whether multiplicity was addressed, which specific contrasts were planned, or whether secondary outcomes were analyzed.
The primary outcome timeframe refers to assessment before and after a 2-week intervention and during washout periods. The registry does not explain which time points would have been combined, prioritized, or compared. The record reports no primary-outcome data, so it is not possible to determine how missing measurements across time points affected the intended comparison.
Analysis populations are also not described. The record does not report whether analyses were intended to follow randomized sequence assignment, include only participants who completed both conditions, or use another population definition. It does not give period-specific completion counts, withdrawal details, or reasons for missing data. In general, excluding participants with incomplete observations can change the composition of an analyzed group; methods for handling missingness can also affect estimates. No trial-specific missing-data method is reported.
The posted record therefore does not establish how multiplicity, incomplete follow-up, or analysis-population choices were handled. These omissions limit interpretation independently of the absence of primary 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 |
|---|---|---|---|
| HD-tDCS | 1 | 4 | 25.0% |
| Sham | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HD-tDCS | 0 of 4 |
| Sham | 0 of 4 |
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 |
|---|---|
| HD-tDCS | 2 of 4 |
| Sham | 1 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | HD-tDCS | Sham |
|---|---|---|---|
| COVID-19 | Respiratory, thoracic and mediastinal disorders | 1 of 4 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HD-tDCS | Sham |
|---|---|---|---|
| Bleeding at electrode site | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 |
| Erythema at collar bone post MEG | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 |
| Headaches | General disorders | 0 of 4 | 1 of 4 |
| Urinary tract infection | Renal and urinary disorders | 1 of 4 | 0 of 4 |
| Fall | Social circumstances | 1 of 4 | 0 of 4 |
| Increased panic attacks | Psychiatric disorders | 1 of 4 | 0 of 4 |
Serious events with the highest arm-level rate: covid-19 (25.0%).
The registry lists serious and other adverse-event counts separately for HD-tDCS and Sham. For HD-tDCS, 4 participants were listed at risk for serious adverse events and 1 was listed as affected; for Sham, 4 were listed at risk and 0 were listed as affected. For other adverse events, the registry lists 4 at risk and 2 affected in HD-tDCS, and 4 at risk and 1 affected in Sham. Deaths are listed as 0 in both groups.
These counts describe the registry’s event summaries; they do not show that an event was caused by the stimulation condition. In a crossover study, participants may receive both conditions, so condition-level at-risk counts should not automatically be interpreted as separate groups of unique people. The record does not explain how events were attributed across periods or whether the same participant contributed events in both conditions.
COVID-19 is listed as the top serious adverse-event term, with a frequency of 25.0%. The record does not provide enough detail to infer causality or to determine the timing of that event relative to treatment. The small listed at-risk counts also mean that these summaries alone cannot characterize the full range or comparative frequency of safety outcomes with precision. They should be read as descriptive registry counts, not as a definitive comparison of risk.
12. What the Result Does, and Does Not, Mean
The record describes a randomized, quadruple-masked crossover study designed to compare HD-tDCS with Sham for language performance in people with lvPPA. It specifies stimulation conditions and lists language performance as the primary outcome. The study is marked completed, with enrollment listed as 6.
The primary result, however, is not reported as an estimate: the registry states that no data were collected for the primary outcome. There is no posted comparison, no measure of uncertainty, and no analysis showing whether language performance changed after either condition. As a result, the registry record cannot support a conclusion that HD-tDCS improved language performance, that it had no effect, or that it was equivalent to Sham.
The absence of a reported primary result should not be treated as a negative finding. A negative finding would require data and an analysis capable of distinguishing an effect from no effect with stated precision. Equivalence would require an appropriate design and analysis with a prespecified margin. Neither is reported in this record. The correct interpretation is that the primary question remains unanswered by the posted results.
The adverse-event counts provide descriptive information for the listed conditions, but they do not resolve the efficacy question. They also do not establish causality, and the registry does not describe how event attribution worked across crossover periods. The secondary outcomes are named, but no analysis results are reported for them.
General statistical reasoning can explain why crossover designs use paired comparisons, why carryover and period effects matter, and why confidence intervals are useful. Those concepts help identify what a complete report would need to convey. They cannot replace missing outcome data or establish what happened to participants’ language performance.
Thus, the registry record documents a study design and some safety counts, but it does not provide the primary outcome evidence needed to judge the language-performance comparison. Any inference about treatment effect, precision, or clinical importance would go beyond the reported results.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a crossover design with a very small registered enrollment and an unreported primary endpoint. Crossover designs can be attractive when outcomes are measured under both conditions in the same participants, because the comparison can account for stable differences between people. That strength depends on measurements being collected in both periods and analyzed with the repeated-measure structure in mind.
The registry lists an enrollment of 6, but states that no primary-outcome data were collected. This makes clear why enrollment alone is not enough to assess a trial’s evidential contribution. Readers need to know who contributed outcome observations, what was measured, how the comparison was estimated, and how uncertain that estimate is. Those elements are not available for the primary language outcome.
The record also illustrates the importance of distinguishing design features from results. Randomization and masking can reduce some risks of bias, while a washout period is intended to address carryover. Neither the presence of these features nor the completed status of the study demonstrates that the planned outcome was measured or that a treatment effect was observed.
Finally, a transparent account of missing data, analysis populations, and multiplicity is especially important when multiple periods, time points, and secondary measures are registered. Without those details and results, statistical interpretation must remain bounded. The main contribution of the record is therefore descriptive: it documents the intended comparison and makes visible the absence of primary efficacy data, rather than providing evidence for a comparative language effect.
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 primary limitation is explicit: no data were collected for the primary language-performance outcome. No treatment contrast, uncertainty interval, or statistical test is available. This prevents assessment of effect direction, magnitude, precision, or clinical relevance.
The registry lists enrollment of 6 but does not report how many participants completed each treatment period, whether all randomized participants received both conditions, or how many contributed to the adverse-event summaries. The number of participants available for any outcome analysis is therefore not reported in the registry record. Withdrawal reasons and missing-data handling are also not reported.
Several design and measurement details are absent. The registry does not identify the language instrument or scoring method, explain how repeated measurements were summarized, or report the planned model for the crossover comparison. Although the Sham-then-HD-tDCS sequence specifies a 16-week washout, the record does not report a carryover assessment or the handling of period and sequence effects.
The record identifies quadruple masking but does not specify the masked roles or procedures. It does not report randomization generation or concealment. It also does not state whether language training was standardized across conditions or how the mentioned imaging and training activities related to outcome collection.
Finally, the secondary outcomes are listed without results, and the registry does not report a multiplicity plan or the trial’s sample-size justification. These limitations mean that neither the primary comparison nor the wider pattern of registered outcomes can be evaluated from the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: HDtDCS in Logopenic Variant PPA: Effects on Language and Neural Mechanisms — NCT03805659.
- Registry record last updated 2024-06-11; status last verified 2024-05.
- Results first posted 2024-06-11.
- 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
This completed study evaluated HD-tDCS and Sham in a randomized, quadruple-masked crossover design focused on language performance in lvPPA. The registry lists enrollment of 6 and identifies language performance after stimulation sessions as the primary outcome.
The HD-tDCS description specifies stimulation of the left posterior temporo-parietal cortex, lasting 20 minutes at an electric current intensity of up to 2mA, once a day for 10 sessions over 2 weeks. Sham is described as no electric current. One sequence description specifies a 16-week washout before the later HD-tDCS period.
The registry states that no data were collected for the primary outcome. It reports descriptive adverse-event counts, but no primary efficacy estimate or analysis results for the listed secondary outcomes. Period-specific completion, analysis populations, missing-data procedures, and the statistical analysis plan are not reported in the registry record. The posted information therefore describes the study design but does not answer whether language performance differed between HD-tDCS and Sham.