Feasibility of Gamma Transcranial Alternating Current Stimulation to Reduce Beta-amyloid Load and Improve Memory: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility of Gamma Transcranial Alternating Current Stimulation to Reduce Beta-amyloid Load and Improve Memory (NCT04646499), a na na study. The primary outcome is Side Effects.

2. Clinical Question

3. Trial Design

The registry classifies this as a completed, single-group study of transcranial alternating current stimulation. It records 14 participants enrolled, an allocation description of NA, and no masking. These features describe a feasibility-oriented study without a separate control arm in the registry record. The record does not identify a randomized comparison or a blinded outcome assessment.

The intervention is named transcranial alternating current stimulation, and the group description specifies gamma stimulation. The condition is mild cognitive impairment. The registry lists the study start as 2021-01-18 and primary completion as 2021-12-31. The phase is recorded as NA. Although the study is marked completed, that status does not itself establish that all outcome data were analyzed or reported.

Side effects are the primary outcome. The listed secondary outcomes concern beta-amyloid load change, memory recall change, paired-associates change, fluency change, and tau change. The registry records seven outcome measures and five analyses, but the specific analytic procedures and the results for the secondary outcomes are not reported in the registry record.

The primary outcome population is described as participants who completed the full protocol. The number in that analysis population and the reasons any participants may not have completed the protocol are not reported in the registry record. No separate comparator is available for distinguishing intervention-related change from time trends, expectations, repeated testing, or other influences. The study design therefore supports a descriptive account of the outcomes observed in this group, but not a controlled estimate of the intervention’s effect relative to an alternative.

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

Analysis population for the primary outcome, as defined in the registry: Only data from participants who completed the full protocol were analyzed.

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 Side Effects, measured over Average of all post-tACS sessions, up to 1 month.

The primary endpoint is an average rating of side effects across the symptoms listed in the registry: headache, neck pain, scalp pain, tingling, itching, burning sensation, increased sleepiness, trouble concentrating, acute mood change, and phosphenes. The scale runs from 0, described as not noticeable, to 10, described as not tolerable. The timeframe is the average of post-stimulation sessions, up to one month. The registry says the average rating across all measures was reported as an indicator of side effects.

This type of outcome is relevant to a feasibility study because participants’ reported experiences can describe tolerability during the intervention period. A combined average offers a summary across the listed symptoms, though it does not show whether a particular symptom was more common or more bothersome than others. Nor does a group average describe the full range of individual experiences. The registry’s analysis population is limited to participants who completed the full protocol; the number included is not reported in the registry record.

The numerical mean and standard deviation for this endpoint are not reported in the registry record. Thus, the direction and typical level of the recorded ratings, their variation among participants, and the precision of the group estimate cannot be assessed from the recorded outcome details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary represent?

The primary outcome is a continuous rating summarized by a mean and standard deviation. In general, a mean is an average of measured values, and the standard deviation describes how much individual observations vary around that average. These are descriptive summaries: they tell readers about the observed data, but do not by themselves show whether a treatment caused a difference or whether an estimate is precise enough to support a particular conclusion.

The outcome description combines ratings across a list of symptoms and across post-stimulation sessions, with the timeframe extending up to one month. The registry says the average rating across all measures was used as an indicator of side effects. It does not provide the numerical average or standard deviation. It also does not clarify the exact calculation sequence used to combine symptoms and sessions, beyond the description of an average across all measures. The numerical endpoint results and further calculation details are not reported in the registry record.

What can a single-group design estimate?

The registry classifies the study as single-group, with allocation listed as NA and masking listed as none. In general, a single-group study can describe measurements collected among participants receiving the intervention. If measurements are made at more than one time, a within-group change may also be described when the relevant results are reported. Such a change is not equivalent to a comparison with an untreated or alternative-treatment group. Without a concurrent comparator, it is difficult to distinguish an intervention-associated change from time effects, repeated measurement, expectations, or other factors.

No randomized comparison is recorded, and the registry explicitly identifies that the arms are not a like-for-like control comparison. Therefore, the design does not provide a controlled estimate of the difference between gamma stimulation and another condition. The record’s classification does not reveal whether any other design features were used beyond those listed; further details are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval expresses a range of values compatible with the observed data and a specified statistical model. Its width reflects uncertainty, including the amount of information in the data and the variability of the outcome. A standard deviation is not a confidence interval: it describes variation among observations rather than directly expressing uncertainty in the estimated mean. The registry record does not report a confidence interval or a numerical standard deviation for the primary outcome, so neither the estimate’s precision nor the observed variability can be assessed from the listed endpoint details.

The enrollment count is 14, but the primary analysis is restricted to full-protocol completers. Since the number of completers is not reported in the registry record, the effective analysis sample size for the primary endpoint cannot be established from the enrollment figure. In general, fewer analyzed observations can make an estimate less precise, while substantial variation in ratings can also limit precision. The actual magnitude of either issue cannot be determined without the outcome and analysis-population results.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. This is a planning exercise, not a report of the study’s observed power and not a description of the single-group design’s actual allocation. The illustration assumes a two-arm comparison, whereas this study is recorded as single-group. Its assumptions should not be mistaken for the study’s own design or for evidence that a particular effect was detected.

In general, sample-size planning asks how many observations a hypothetical study would need under stated assumptions. A planning result depends on the assumed effect, variability, significance level, and analysis method. It does not establish that the planned study enrolled that number, nor does it guarantee a meaningful result. The registry record does not report a sample-size justification for the trial itself, and no numerical planning results are included in the registry record for this explanation. The stated assumptions alone are insufficient to evaluate a proposed sample size or infer an observed effect.

What analytic details are absent?

The registry records seven outcome measures and five analyses, but the detailed statistical methods are not reported in the registry record. In particular, the record does not state which comparisons or models were used for each outcome, whether estimates were adjusted, or how any repeated observations were handled. The primary endpoint is described as a mean with standard deviation, but no inferential procedure is specified in the available record. These omissions limit reproducibility and make it difficult to assess whether the analysis matched the outcome structure.

In general, statistical interpretation depends on more than an outcome label. The analysis population, handling of missing observations, assumptions of the model, and method for expressing uncertainty all affect what a result means. Those details should be distinguished from general statistical principles: they cannot be attributed to this study unless documented. For this study, the listed outcome definitions and design classifications are available, while the numerical primary result and detailed analysis plan are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Gamma Stimulation Group")
n   <- c(13)
m   <- c(0.53)
sp  <- c(0.65)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Gamma Stimulation Group  13  0.530  0.650  0.137  0.923

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes involving beta-amyloid load, tau, and memory recall, paired associates, and fluency. It also records seven outcome measures and five analyses. The record does not state how the analyses correspond to the outcomes, whether a hierarchy of outcomes was prespecified, or whether any adjustment for multiple comparisons was used. Those details are not reported in the registry record.

In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance. A prespecified outcome hierarchy or an adjustment procedure can help make interpretation more transparent, but the appropriate approach depends on the study aims and analysis plan. No particular multiplicity method can be attributed to this study from the recorded information.

The primary endpoint analysis is described as including only participants who completed the full protocol. The count of those participants, the amount of missing outcome data, and the reasons for any missingness are not reported in the registry record. The record does not explain whether incomplete observations were excluded, imputed, or handled by another method. Consequently, the potential influence of missing data on the primary estimate cannot be assessed.

In general, restricting analysis to completers can yield a group that differs from all enrolled participants if completion is related to outcomes or participant characteristics. This is a methodological consideration, not evidence that such a difference occurred in this study. The registry also records 13 participants at risk for the listed adverse-event categories, but that safety denominator should not be assumed to be the primary endpoint analysis population.

The record does not report an intention-to-treat analysis or another named analysis population. It also does not report interim analyses or stopping rules. These omissions leave important aspects of the analysis and reporting process unclear; they do not establish that a particular procedure was or was not used outside the registry description.

12. 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.

The registry lists 13 participants at risk in the Gamma Stimulation Group for serious adverse events and 0 participants affected. It also lists 13 participants at risk for other adverse events and 0 affected. Deaths are recorded as 0. No serious adverse-event terms are listed. These are the event counts recorded for the group, not a comparison with a control group.

Zero recorded events in these categories means that the registry lists none among the participants counted at risk. It does not establish that the possibility of an event is absent, and it cannot by itself describe the range of experiences among participants. In general, event counts from a limited group may provide imprecise information about uncommon events. No confidence interval or further safety analysis is reported in the registry record.

The adverse-event denominator is distinct from the primary outcome’s stated population of full-protocol completers. The number of primary outcome participants is not reported in the registry record, so the safety counts should not be used to fill that gap. The registry does not list serious-event terms, but that should be interpreted as no terms listed in the record, rather than as a detailed narrative account of all safety monitoring. Timing, event definitions beyond the registry categories, and attribution to the intervention are not reported in the registry record.

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

This record describes a completed feasibility study of gamma-band transcranial alternating current stimulation in people with mild cognitive impairment. Its primary outcome concerns participants’ ratings of side effects over post-stimulation sessions, up to one month. The recorded design is single-group and unmasked, with no separate comparator identified. These registry entries establish the study’s focus and structure, but they do not establish an efficacy result.

The project summary describes aims related to beta-amyloid load and memory performance. The registry lists beta-amyloid load change, memory recall change, paired-associates change, fluency change, and tau change as secondary outcomes. Numerical findings for those measures are not reported in the registry record. The numerical mean and standard deviation for the primary side-effect endpoint are also not reported in the registry record. It is therefore not possible to describe the direction, magnitude, or precision of the measured outcomes from these details.

The registry records 14 enrolled participants, while the primary analysis is described as limited to full-protocol completers. The number of completers is not reported in the registry record. Safety counts are recorded separately for 13 participants at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. Those counts describe the listed safety categories in this group; they do not provide a controlled estimate or show that events cannot occur.

In general, a single-group feasibility study can contribute descriptive information about study procedures and measured experiences. It cannot, without an appropriate comparator, isolate the effect of an intervention from other influences. The posted registry entries leave the outcome estimates and much of the analysis approach unspecified. The appropriate reading is therefore limited: the record identifies the questions and measurement plan, but does not report the numerical evidence needed to judge the primary outcome or the listed biomarker and memory outcomes.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between its stated scientific aims and its primary endpoint. The project summary concerns lowering beta-amyloid load and improving memory, while the primary outcome is a side-effect rating. The registry lists biomarker and memory changes as secondary outcomes. Keeping those roles separate matters: a tolerability measure and a cognitive or biomarker measure answer different questions and should not be treated as interchangeable evidence.

The single-group design also shapes what can be learned. Descriptive outcome data can characterize observations in the treated group, but without a control group they do not establish what would have happened under another condition. This limitation is especially important when interpreting changes over time, because the design does not separate an intervention-associated change from other possible influences.

Reporting the analysis population is another key statistical issue. The registry says that only full-protocol completers contributed to the primary analysis, but does not report their number. Enrollment is recorded as 14. Without the number analyzed and information about missing observations, readers cannot determine how the analyzed group relates to everyone enrolled or assess the possible impact of incomplete data.

Finally, the registry identifies multiple outcome measures and analyses but does not report detailed methods or numerical results. Transparent estimates, uncertainty measures, and analysis-population details would be needed to assess the magnitude and precision of the outcomes. The recorded safety counts provide a limited descriptive account, not a comparative safety estimate. These features make the study useful to consider as a feasibility design while also making careful boundaries around interpretation essential.

15. 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 for statistical interpretation is that the registry record does not report the numerical result for the primary endpoint. Without the mean and standard deviation, it is not possible to assess the group’s average side-effect rating or the variability of individual ratings. The numerical results for the listed secondary outcomes are also not reported in the registry record, so no conclusion about observed memory or biomarker changes can be drawn from these details.

The study is recorded as single-group, with no masking and no separate comparator. As a result, any within-group changes, if available elsewhere, would not by themselves isolate an intervention effect. The registry’s design information also does not describe the timing or analytic handling of baseline measurements, and further details are not reported in the registry record.

The enrollment count is 14, but the primary endpoint analysis included only participants who completed the full protocol. The number of completers, reasons for non-completion, and extent of missing outcome data are not reported in the registry record. This makes it difficult to assess the analysis denominator and the potential for selection related to completion.

The registry records seven outcome measures and five analyses but does not give detailed analysis methods, multiplicity procedures, or uncertainty estimates. It also does not report whether analyses were adjusted or how repeated measurements were handled. The safety record lists 13 participants at risk and no events in the specified categories, but does not provide a comparator or further event-level detail. These limitations apply to interpretation of the registry record and should not be mistaken for evidence that any unreported procedure or outcome was absent from the broader study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility of Gamma Transcranial Alternating Current Stimulation to Reduce Beta-amyloid Load and Improve Memory — NCT04646499.
• Registry record last updated 2023-07-27; status last verified 2023-07.
• Results first posted 2023-07-27.
• 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.

19. Record Summary

NCT04646499 is recorded as a completed, single-group study of gamma-band transcranial alternating current stimulation in people with mild cognitive impairment. Enrollment was 14. The study was unmasked, with allocation listed as NA. The registry records a start date of 2021-01-18 and a primary completion date of 2021-12-31.

The primary outcome was a mean side-effect rating across listed symptoms and post-stimulation sessions, up to one month; only full-protocol completers were analyzed. Its numerical result and the number of completers are not reported in the registry record. Secondary outcomes included beta-amyloid, tau, and memory measures, but their numerical results are also not reported in the registry record. Safety listings record 0 serious events, 0 other events, and 0 deaths among 13 participants at risk for each event category.