Treating Primary Progressive Aphasia (PPA) Using tDCS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treating Primary Progressive Aphasia (PPA) Using tDCS (NCT04566731), a randomized na study. The primary outcome is Western Aphasia Battery Aphasia Quotient (WAB-AQ).

2. Clinical Question

The study asks whether adding real rather than sham stimulation to mCILT is associated with a different pattern of language performance. Its primary measure is change in WAB-AQ score, with the registry describing baseline-to-12-week assessment and baseline-to-24-week assessment when available. The study also plans to examine brain imaging and network properties in relation to severity and performance changes, but those questions are distinct from the primary outcome comparison.

The registry describes a randomized crossover study, so participants were assigned to treatment sequences rather than only to a single parallel-group treatment. The summary describes the intended sequence as real stimulation plus therapy and sham stimulation plus therapy, or the reverse. This design can support within-person comparisons, but interpretation depends on the recorded outcome data and analysis. The posted information does not include numerical WAB-AQ changes, an estimated treatment contrast, or a confidence interval. It therefore does not establish the size or precision of any difference between the stimulation conditions.

3. Trial Design

The registry describes a randomized crossover study of tDCS paired with modified constraint-induced language therapy. Its enrollment is 23, and its status is completed. The participants described in the study summary have non-fluent/agrammatic or semantic-variant primary progressive aphasia. The listed treatment sequences are tDCS plus CILT followed by sham tDCS plus CILT, and the reverse sequence. Each participant’s sequence allows the study to compare performance across treatment conditions, subject to the assumptions and analysis appropriate for a crossover design.

The intervention description specifies 10 daily sessions of stimulation, paired with therapy. For the real stimulation condition, the arm description gives a session duration of 20 minutes and a current of 1.5 mA, with electrodes positioned over F7 and O1 using the 10-20 EEG mapping system. The sham condition is also described as paired with language therapy and uses the stated electrode positions. The description of the real-treatment arm ends mid-sentence in the registry record, so further details of its therapy procedure are not reported in the registry record.

The study summary says language testing and imaging were planned before and after treatment, immediately after treatment, and during follow-up up to 24 weeks. The primary outcome timeframe is stated as baseline to 12 weeks and baseline to 24 weeks when available. The registry labels masking as triple, while the brief summary describes the study as double-blind. The precise roles covered by the masking label are not reported in the registry record. The protocol’s allocation procedures, sequence-generation details, washout arrangements, and rationale for the chosen sample size 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: A total of 3 participants did not qualify at the time of enrollment due to low MMSE scores (2) and diagnosis change that no longer met our PPA criteria (1). A total of 2 participants dropped out of the study before they were randomized due to travel concerns.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 24 week follow-up data are not available for individuals randomized to the tDCS + CILT first, then Sham tDCS + CILT group because there is no 24 week follow-up for the first arm. 24 week follow-up data are not available for individuals randomized to the Sham tDCS + CILT first, then tDCS + CILT group because there is no 24 week follow-up for the first arm.

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.

6. Primary Endpoint

The registry lists the primary outcome as Western Aphasia Battery Aphasia Quotient (WAB-AQ), measured over Baseline to 12 weeks; baseline to 24 weeks when available.

The primary outcome is change in Western Aphasia Battery Aphasia Quotient (WAB-AQ) score. The registry describes the measure as an assessment of overall aphasia recovery, recorded as a score on a scale. Scores range from 0-100, with higher scores representing better outcomes. The listed severity categories are 0-25 for very severe, 26-50 for severe, 51-75 for moderate, and 76-above for mild; a score of 93 or higher is considered recovered.

Using change in a language score gives the study a way to describe performance over time, rather than relying only on a single post-treatment score. The stated comparisons begin at baseline and extend to 12 weeks, with baseline-to-24-week data included when available. In general, baseline-adjusted or change-based comparisons can help account for where participants started, although the exact model used is not reported in the registry record.

The registry identifies the outcome as a mean with standard deviation, but the registry entries do not include the observed means, standard deviations, changes, or comparison estimates. Numerical outcome results and their uncertainty are therefore not reported in the registry record. The description of what WAB-AQ measures should not be mistaken for evidence of a change in this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized crossover design with two treatment conditions: tDCS plus language therapy and sham tDCS plus language therapy. In a crossover trial, participants receive conditions in sequence, so each participant may contribute measurements under more than one condition. General statistical rationale: comparing measurements within the same person can reduce the influence of stable differences between people. The comparison still needs an analysis that accounts for the paired structure and the order in which conditions were received. The analysis method used for this trial is not reported in the registry record.

What does a crossover comparison need to account for?

General statistical explanation: a crossover design can be affected by period effects, meaning outcomes may change over time for reasons separate from the treatment condition. Sequence can also matter if the order of conditions is associated with outcome patterns. Carryover is a further concern when an effect from an earlier condition could remain during a later period. These are issues to consider in crossover studies, not claims that they affected this trial. Details of washout, period or sequence effects, and carryover assessment are not reported in the registry record.

The brief study summary describes assessments before and after treatment, immediately after treatment, and during follow-up up to 24 weeks. The primary outcome timeframe is baseline to 12 weeks and baseline to 24 weeks when available. These timepoints raise an interpretive question: the treatment contrast could be defined at a particular time or across multiple times. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. The exact timepoint-specific comparisons and their statistical model are not reported in the registry record.

What does the outcome scale represent?

WAB-AQ is a continuous score on a scale from 0-100, with higher scores indicating better outcomes. The registry gives severity bands and identifies a score of 93 or higher as recovered. The primary outcome is described as a mean with standard deviation. General statistical explanation: a mean summarizes the center of a set of scores, while a standard deviation describes variation among scores around that mean. These summaries do not by themselves show the difference between treatment conditions, account for repeated measurements, or convey the uncertainty of a treatment contrast. The posted primary outcome estimates are not reported in the registry record.

A treatment effect estimate would describe the comparison the analysis targets, such as a contrast in change between conditions. A confidence interval would communicate the precision of that estimate under the model. A p-value, if used, would summarize how compatible the observed data are with a null hypothesis and the assumptions of the test. These quantities answer different questions: an estimate describes direction and magnitude, an interval describes uncertainty, and a p-value does not measure clinical importance. None of those numerical primary-outcome results is reported in the registry record.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration computed from an observed effect, rather than the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. General statistical explanation: a planning calculation explores how a proposed effect and design assumptions relate to the amount of information a study might need. It is not an observed result and should not be called observed power. No calculated sample-size values are included in the registry record, and the original sample-size rationale is not reported in the registry record.

The record gives enrollment as 23, but enrollment alone does not establish how many participants contributed data to each outcome analysis or how many had complete follow-up. The analysis population, exclusions, and participant flow are not reported in the registry record. This matters because estimates and their precision depend on the data actually analyzed and on how missing measurements are handled.

How should multiple outcomes and timepoints be read?

The listed primary measure is one scale, but it has multiple assessment times, and the record explicitly says the primary outcome has several categories or time points. If several comparisons are examined, general statistical explanation: the chance of at least one apparently notable result can increase when many tests are considered. A prespecified primary comparison, or an adjustment strategy, can clarify interpretation. Whether the trial used a multiplicity plan, which comparisons were prespecified, and whether any adjustment was made are not reported in the registry record.

The study also describes brain imaging and network analyses, alongside behavioral testing. Those planned analyses may address questions about brain properties and response, but the fact that they are described does not provide their results or establish their relationship to WAB-AQ. The statistical methods for the imaging and network analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described as WAB-AQ change, but the record says that it has several categories or time points and is not reduced to one comparison. The stated timeframe includes baseline to 12 weeks and baseline to 24 weeks when available. Without a single reported contrast, readers cannot tell which timepoint or comparison is intended to carry the primary interpretation. The protocol’s hierarchy of comparisons, any prespecified testing sequence, and any adjustment for multiple comparisons are not reported in the registry record.

General statistical explanation: examining multiple outcomes or timepoints can make a chance finding more likely if each is treated as a separate test. Prespecifying a primary comparison or using an appropriate multiplicity method can help keep the interpretation aligned with the study question. This general issue does not indicate that a particular result in this trial is false or that a particular adjustment was needed; the registry information does not document the analysis plan.

Some follow-up data are explicitly unavailable. The outcome description says 24-week follow-up data are not available for individuals randomized to tDCS plus CILT first, then sham tDCS plus CILT, because there is no 24-week follow-up for the first arm. It also says 24-week follow-up data are not available for individuals randomized to sham tDCS plus CILT first, then tDCS plus CILT. These statements should be read as limits on the listed follow-up data, not as evidence about why individual measurements are missing.

The methods for handling missing observations, the number of participants analyzed at each timepoint, and the analysis population are not reported in the registry record. Nor are interim analyses, imputation procedures, or sensitivity analyses reported in the registry record. These omissions limit assessment of how missing data and the multiple timepoints affected the reported findings. No numerical primary outcome findings are available to evaluate alongside those design questions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hip replacement (5.6%), chest pain (5.6%).

The registry lists 18 participants at risk for serious adverse events in each treatment group. It records 1 participant affected in the tDCS plus CILT group and 1 in the sham tDCS plus CILT group. It lists 18 at risk for other adverse events in each group, with 4 affected in the tDCS plus CILT group and 3 in the sham tDCS plus CILT group. Deaths are recorded as 0 in both groups.

The top serious adverse-event terms listed are Hip replacement and Chest pain, each shown as 5.6%. The registry entries do not state which treatment group each term occurred in or provide further event-level context, so these terms should not be assigned to a group based on the summary. The counts also do not establish whether an event was caused by stimulation, therapy, the underlying condition, or another factor. Causal attribution is not reported in the registry record.

General statistical explanation: safety counts are descriptive summaries. In a crossover study, the meaning of a group label can depend on how the registry organized treatment periods and sequences. The listed at-risk counts and affected counts should therefore be read as reported, not as a complete account of event timing or exposure. The registry entries do not provide event definitions, severity details beyond the serious/non-serious grouping, exposure-adjusted rates, or statistical comparisons. These figures do not answer the primary WAB-AQ question.

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

This record describes a trial designed to compare real and sham tDCS, each paired with language therapy, in people with primary progressive aphasia. It identifies WAB-AQ change as the primary outcome and describes follow-up assessments, a randomized crossover structure, and planned imaging and network analyses. Those details explain the question the investigators intended to study; they are not themselves evidence of a treatment effect.

The registry entries do not contain numerical WAB-AQ results. There is no reported change by condition, comparison estimate, confidence interval, or p-value in the information. Consequently, the direction and size of any difference and the precision of the estimate cannot be assessed from this record summary. The outcome’s severity ranges and recovery threshold describe the scale, not what participants achieved in the trial.

General statistical explanation: even a measured difference would need to be interpreted in relation to its uncertainty, the crossover analysis, missing data, the chosen timepoint, and any multiplicity considerations. A point estimate alone does not show how stable the result is; a confidence interval helps show precision, while statistical significance alone would not establish the importance of a difference. In this case, those numerical results are not reported in the registry record, so such interpretation is not possible.

The safety section gives counts of affected participants and lists serious-event terms, but it does not establish that an event was caused by a study intervention. Nor do those counts substitute for the primary outcome. The registry entries do not support a conclusion about whether the treatment conditions did or did not produce a meaningful difference in language scores. They support a careful description of the trial’s design and the limits of the posted results.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its randomized crossover design asks participants to contribute information under both real and sham stimulation conditions, with language therapy paired with each. General statistical rationale: within-person comparisons can help separate treatment-condition differences from stable variation between people. That advantage relies on appropriate handling of repeated observations and the order of treatment periods, making the analysis central to interpretation.

The clinical question is represented by a continuous language score measured over time. Repeated assessments can describe whether scores change after treatment and at follow-up, but they also create choices about which timepoint and contrast should anchor the primary conclusion. The registry record identifies baseline-to-12-week and baseline-to-24-week timeframes and notes that the outcome includes several categories or time points. This makes transparent reporting of the target comparison and multiplicity approach especially important.

The record also describes imaging and network analyses in addition to language performance. Statistically, these questions differ: a behavioral outcome comparison estimates changes in a clinical measure, while network analyses seek associations between brain properties and severity or performance changes. Findings from one type of analysis would not automatically establish findings in the other. Numerical results and detailed methods for these analyses are not reported in the registry record.

The key lesson for reading this page is to separate design information from evidence of an outcome. The registry describes a completed study and gives its planned measure and safety counts, but the numerical primary outcome comparison is not reported in the registry record. That distinction matters because a detailed design can explain what a study set out to test without revealing the estimate, uncertainty, or robustness of its result.

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 main limitation for interpreting this trial from the posted information is that numerical primary outcome results are not reported in the registry record. Although WAB-AQ is identified as the primary measure, there are no displayed changes by condition or numerical treatment contrast, and no confidence interval or p-value. The record also notes multiple outcome categories or timepoints without reducing them to one comparison, limiting identification of a single result to interpret.

The outcome description flags missing 24-week follow-up data for both treatment sequences, including the stated lack of a 24-week follow-up for the first arm in the sequence that begins with tDCS plus CILT. The extent of missingness at other timepoints, reasons for missing data, and methods used to handle missing observations are not reported in the registry record. The number enrolled is not enough to determine the number contributing to each analysis.

The registry calls the study randomized and crossover, but the methods needed to evaluate the implementation and analysis are not reported in the registry record. These include sequence-generation details, allocation concealment, washout arrangements, the handling of period and sequence effects, and any assessment of carryover. The registry labels masking as triple, while the summary calls the study double-blind; the roles covered by masking are not reported in the registry record.

The listed intervention description for the real-treatment arm is incomplete, and further details of the therapy procedure are not reported in the registry record. The sample-size rationale, analysis populations, multiplicity plan, and interim analyses are also not reported in the registry record. These limits do not show that the design or conduct was inadequate; they restrict what can be assessed from the available record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treating Primary Progressive Aphasia (PPA) Using tDCS — NCT04566731.
• Registry record last updated 2025-11-13; status last verified 2025-10.
• Results first posted 2025-11-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This completed randomized crossover study examines tDCS paired with modified constraint-induced language therapy versus sham tDCS paired with the same therapy in people with primary progressive aphasia. The registry lists enrollment of 23 and identifies WAB-AQ change as the primary outcome, with baseline-to-12-week and baseline-to-24-week assessment when available.

The study summary describes language testing and imaging, while the primary outcome description gives the score range and interpretation. The record notes that the primary outcome includes multiple categories or timepoints and is not reduced to one comparison. Numerical WAB-AQ findings, the analysis model, and the methods for handling missing data are not reported in the registry record.

Safety counts are listed for serious and other adverse events in both treatment groups, with 0 deaths recorded in each. These descriptive counts do not establish causation and do not answer the primary outcome question.