Transmagnetic Stimulation Pilot in Early Stage Alzheimer's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transmagnetic Stimulation Pilot in Early Stage Alzheimer's Disease (NCT05292222), a na na study. The primary outcome is Change in Connectivity Measure of the TGd Parcellations..

2. Clinical Question

This clinical question is primarily about change within the treated group. It is not a randomized comparison of stimulation against another intervention. Consequently, even if a before-and-after change were reported, the study structure alone would not distinguish an intervention-related change from other explanations, such as natural variation or changes over time. No such observed outcome is available in the registry record, so the direction and size of change cannot be assessed.

The registry summary presents the study as a pilot using resting-state functional MRI to target dysfunctional large-scale brain networks in early-stage Alzheimer disease. That rationale describes the intended approach, not a demonstrated effect. The record does not provide further detail about participant-level eligibility, the criteria used to identify network targets, or the clinical outcomes beyond the connectivity measure.

3. Trial Design

This is a completed, single-group pilot study of intermittent theta burst stimulation in people with early-stage Alzheimer disease. The registry records an enrollment of 15. It lists allocation as not applicable and masking as none. All subjects were to receive the intervention; the record does not describe a separate control arm or a randomized assignment.

The intervention description specifies a total of 5 treatments over a 2-week period. Stimulation was directed to the right TGd region and two additional sites within large-scale brain networks. The official title identifies resting-state functional magnetic resonance imaging as the guide for targeting. Details about how the target sites were selected, the stimulation settings, treatment delivery procedures, and adherence are not reported in the registry record.

The primary outcome is a continuous connectivity measure: change in the number of abnormal connections of the TGd parcellation. The registry describes assessment at 9 weeks and states that the measure is calculated from the difference between follow-up and baseline. It identifies the mean as the reported summary and standard deviation as the measure of dispersion. Although the outcome description states that higher values indicate more abnormal connections, the exact sign convention for the change score is not reported.

The record gives a study start date of 2022-06-17, a primary completion date of 2023-11-07, and a status of completed. These are administrative study dates; they do not establish when each participant received treatment or completed follow-up. The record does not report participant flow, withdrawals, protocol deviations, or the number contributing data to the primary outcome.

There is no statistical analysis listed in the registry record. The analysis plan, including any model specification, adjustment strategy, confidence interval procedure, and handling of repeated measurements, is not reported. The enrollment figure is not accompanied by a reported sample-size justification. Therefore, it should not be interpreted as evidence that the study was designed to attain a particular precision or probability of detecting a specified effect.

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: 4 participants screen failed with a low MMSE, 1 participant withdrew before receiving any treatment.

Overall Study

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 Change in Connectivity Measure of the TGd Parcellations., measured over 9 weeks.

The primary endpoint is change in the number of abnormal connections in the TGd parcellation, measured from baseline to follow-up at 9 weeks. The registry describes the outcome as a continuous measure, summarized by its mean and standard deviation. The parcellation is said to have 378 possible connections, with a range of 0-378. Higher values indicate more abnormal connections of the parcellation before and after treatment.

Connectivity measures can represent patterns of relationships among brain regions. In this study, counting abnormal connections offers a way to describe the targeted network feature numerically rather than relying only on a general characterization of connectivity. Assessing change from baseline is intended to capture whether the measured count differs at follow-up from its starting value. This explanation of the measure is general; it does not establish that a change occurred in this study.

The endpoint description does not state whether the change score is calculated as follow-up minus baseline or baseline minus follow-up. That distinction matters when interpreting the sign: a positive or negative value could have different meanings under different conventions. The record also does not report the observed mean change, its standard deviation, or a confidence interval. The stated range and interpretation of higher raw values do not substitute for those results.

The endpoint is a connectivity measure, not a direct report of symptoms, daily functioning, or quality of life. The registry record does not report a relationship between this measure and a clinical outcome. Accordingly, the measure can describe the prespecified imaging question, but the record does not support conclusions about changes in participants' clinical condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: a change in the number of abnormal connections of the TGd parcellation. The registry identifies the mean as the summary measure and the standard deviation as the measure of dispersion. In general, a mean describes the average value across observations, while a standard deviation describes how dispersed individual values are around that average. Neither one is reported as an observed result in the registry record.

What does a change score represent?

In general, a change score is formed by comparing a participant's follow-up measurement with that participant's baseline measurement. It can be useful when the scientific question concerns how a measure evolves within participants. The registry says the primary outcome is the difference between follow-up and baseline, but it does not specify the subtraction order. That omission prevents interpreting the sign of a hypothetical change value. The record also does not state whether the reported mean would be calculated from individual change scores or through another model-based approach.

Why does variability matter?

General explanation: variability describes how much measurements differ among participants. A standard deviation is one common way to summarize that spread for a continuous measure. When individual responses vary considerably, an average alone may conceal that heterogeneity. Conversely, a small spread can indicate that observations are clustered closer to the mean. The endpoint description names a standard deviation, but the value is not reported, so the observed variability cannot be assessed.

A confidence interval is a general method for communicating uncertainty around an estimate. Its interpretation depends on the statistical procedure and assumptions used to construct it. A confidence interval would help readers judge the precision of a mean change estimate, but no interval or method for calculating one is listed in the registry record. A p-value, if one had been reported, would address a different question under a specified statistical model; it would not by itself show the size or clinical importance of a change. No p-value or hypothesis test is reported.

What does the single-group structure mean for analysis?

With one group receiving the intervention, a natural descriptive analysis could compare baseline and follow-up measurements within that group. This is a general description of possible analytic approaches, not a claim about what was done. Such analyses can characterize change over time, but they do not create the counterfactual comparison needed to estimate what would have happened to the same participants without the intervention. The registry lists no analysis, so the actual statistical procedure is not reported.

For a continuous repeated measure, possible approaches in general include summarizing individual change scores or modeling measurements over time. These choices can differ in their assumptions and in how they handle participants with incomplete measurements. The record does not specify which approach was used, whether baseline values were included as covariates, or whether any adjustment was made for other variables. No model diagnostics, assumptions checks, or sensitivity analyses are listed.

How should planning illustrations be understood?

The registry's planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also state that the effect to detect is a stated fraction of the observed effect. Those are assumptions for a planning illustration, not a description of this study's design: this trial is single-group and has no like-for-like control comparison. The registry does not report the study's own sample-size justification. Any illustration based on the observed effect should be treated as a planning exercise rather than observed power or evidence that the trial had a particular probability of detecting an effect.

General explanation: a sample-size calculation depends on assumptions about the effect to be detected, variability, significance level, allocation, and analysis method. If those assumptions change, the resulting planning estimate can change. Such estimates are prospective planning aids; they do not show what the trial actually observed. The available record does not state a design-based sample-size target or the rationale for enrolling 15 participants.

Why does over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. When a model understates variability, standard errors can be too small and uncertainty can appear narrower than it is. The relevance of this issue depends on the outcome distribution and analysis method. The registry record does not report a model or diagnostic assessment, so there is no basis to determine whether over-dispersion was evaluated or relevant to the analysis.

The count of abnormal connections is bounded by the stated range of 0-378. General statistical methods may account for bounded or count-valued outcomes differently from methods designed for measurements that can take any value on a continuous scale. The registry nevertheless identifies the outcome as continuous and the summary as a mean with standard deviation. It does not report whether the outcome was modeled as continuous, count-valued, or otherwise transformed for analysis. No additional distributional assumptions should be inferred.

Finally, the record's absence of an analysis entry means the statistical plan cannot be reconstructed from the registry information. The exact estimand, handling of incomplete follow-up, confidence interval method, and any prespecified decision threshold are not reported in the registry record. These details would be needed to evaluate how closely an eventual analysis followed the intended plan.

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("Intermittent Theta Burst Stimulation")
n   <- c(10)
m   <- c(0.5)
sp  <- c(25)
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  Intermittent Theta Burst Stimulation  10  0.500  25.000  -17.384  18.384

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no analyses. It does not report a statistical analysis plan or state whether additional outcomes were considered in the full study protocol. Therefore, it is not possible to determine whether there were multiple hypotheses, whether any multiplicity adjustment was planned, or how the primary endpoint was prioritized relative to other measures.

Multiplicity is a general concern when many statistical tests are conducted: the chance of at least one apparently notable result can increase as the number of tests grows. Methods to address multiplicity depend on the number and relationship of the questions and on the analysis plan. The registry record does not provide enough information to assess whether multiplicity arose or how it was handled.

Missing-data methods are not reported in the registry record. The record does not state how many participants completed the 9-week assessment, whether any primary outcome measurements were unavailable, or how incomplete observations would be handled. It also does not describe an imputation approach, a complete-case analysis, or sensitivity analyses. The difference between the enrollment of 15 and the safety denominator of 10 does not establish the number with missing primary outcome data; those figures refer to different reported information.

The analysis population is also not described. The registry does not say whether outcome analyses would include all enrolled participants, only those who received treatment, or only those with both baseline and follow-up measurements. No exclusions or protocol deviations are reported. These omissions make it difficult to assess the representativeness of any analyzed group, even if an outcome estimate were available.

Because the primary result and analysis details are absent, readers cannot evaluate the impact of missingness, the number of tests, or the choice of analysis population on the findings. These are not necessarily flaws in conduct; they are limitations of what the registry record reports.

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.

Most frequent non-serious adverse event terms

The registry lists one safety group, titled Intermittent Theta Burst Stimulation. For serious adverse events, it records 10 participants at risk and 0 affected. For other adverse events, it records 10 participants at risk and 10 affected. It also records 0 deaths. No serious adverse-event terms are listed.

These figures are counts among the participants identified as at risk in the safety record. The registry separately records enrollment of 15, but it does not explain why the safety denominator is 10 or whether all enrolled participants were included in safety monitoring. The difference between those totals should not be interpreted as a particular pattern of withdrawal, exposure, or missingness; the reason is not reported in the registry record.

General explanation: an observed count of zero serious events means no serious events were recorded among the participants included in that category. It does not establish that the risk is absent, particularly when the group is small, and it does not describe events that may not have been captured or reported. The record does not provide event definitions, severity grading details, timing, duration, relatedness assessments, or a breakdown of the other adverse events.

The figures are descriptive safety information and do not establish a comparison with another treatment or with no treatment. The record contains no separate control group. The safety counts should therefore be read as the reported experience in the listed group, without extrapolating to a broader population or making a treatment recommendation.

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

The registry record documents a completed pilot study that enrolled 15 participants with early-stage Alzheimer disease and planned intermittent theta burst stimulation guided by resting-state functional MRI. It describes a primary imaging outcome based on change in the number of abnormal TGd parcellation connections at 9 weeks. It does not report the observed change, its standard deviation, or an analysis of that outcome.

As a result, the record does not show whether the connectivity measure increased, decreased, or remained similar from baseline to follow-up. It does not quantify the size or precision of any change, and it does not report a statistical test. A statement about the planned measurement is not a result. The endpoint's stated range and interpretation of higher values do not reveal the participants' actual measurements.

The study also cannot provide a randomized estimate of the difference between stimulation and a comparator because no control group is described. General interpretation: a change measured before and after an intervention in a single group may be informative descriptively, but it cannot by itself determine what would have happened over the same period without the intervention. This design limitation is separate from the absence of a reported endpoint result.

The safety record reports 0 serious adverse events among 10 participants at risk, 10 participants affected by other adverse events among 10 at risk, and 0 deaths. These are descriptive counts, not comparative risk estimates. They do not, by themselves, establish the likelihood of events outside the recorded group or provide enough detail to characterize the non-serious events.

The registry's completed status should not be taken to mean that all intended outcomes or analyses are available in the record. The primary result, participant flow, missing-data approach, and analysis population are not reported in the registry record. Interpretation must remain limited to the design and information actually recorded.

14. Why This Trial Matters Statistically

This study is statistically notable because it connects an imaging-guided intervention with a network-level measurement in a pilot setting. The primary endpoint is defined as a change in abnormal connections of the TGd parcellation, making the measurement specific to the target described in the registry. That specificity can help frame a future research question, while also making clear that the outcome is an imaging measure rather than a direct clinical outcome.

The single-group design illustrates an important distinction between measuring change and estimating a comparative treatment effect. A baseline-to-follow-up measure can describe what happened over time in the observed group. Without a concurrent comparator, it cannot separate a possible intervention effect from other explanations. The distinction is relevant to all before-and-after studies, regardless of the biological rationale for an intervention.

The record also highlights why reporting the estimate and its uncertainty matters. An endpoint definition alone cannot show whether a change was large or small, consistent or variable, or estimated precisely. Here, the primary result and analysis are not reported. Enrollment of 15 and a completed status do not fill that gap; neither establishes the observed outcome or its precision.

Planning illustrations can be useful for considering how assumptions relate to a future study, but they are not substitutes for a prespecified design rationale or observed findings. The record's stated planning assumptions involve two arms, while the trial itself is single-group. Keeping those purposes distinct helps avoid interpreting planning calculations as properties of this study's design or as evidence of observed efficacy.

Finally, the safety information demonstrates the importance of denominators and context. The registry reports 10 participants at risk in its safety group, distinct from the total enrollment of 15, without explaining the difference. Reporting participant flow and outcome availability would help readers understand which group contributed to each analysis. These are reporting and interpretive considerations, not conclusions about study conduct.

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 most immediate limitation is that the primary outcome result is not reported in the registry record. The record names the measure, scale, and timeframe, but does not give the mean change or standard deviation. This prevents assessment of the outcome's direction, magnitude, and variability. It also means that no confidence interval or test result can be interpreted.

The single-group design has no separate control arm and no randomized comparison. Any within-group change, if reported, would be difficult to distinguish from changes over time or other influences. The record does not describe masking, and it lists masking as none. The implications of that design for measurement or conduct cannot be assessed further from the registry information.

Several details needed to understand the endpoint are absent. The subtraction order for the change score is not stated, so the sign of a reported value would be ambiguous without clarification. The record does not give the method for selecting the two additional stimulation sites, further technical treatment details, or participant-level eligibility criteria. It also does not report how many participants completed the 9-week assessment.

The analysis plan and analysis population are not reported. There is no information about missing-data handling, adjustment for other variables, model assumptions, or sensitivity analyses. The record lists no analyses and does not provide a sample-size justification. Thus, neither the inferential approach nor the intended precision can be evaluated.

The safety denominator is 10, whereas enrollment is 15. The registry does not explain the difference, and it does not describe the non-serious adverse events beyond the count affected. This limits interpretation of both the safety counts and participant accounting. These constraints reflect information absent from the registry record; they do not establish that particular procedures or analyses were or were not conducted outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transmagnetic Stimulation Pilot in Early Stage Alzheimer's Disease — NCT05292222.
• Registry record last updated 2025-01-07; status last verified 2023-11.
• Results first posted 2025-01-07.
• 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

NCT05292222 is a completed single-group pilot study of resting-state functional MRI-guided intermittent theta burst stimulation in early-stage Alzheimer disease. The registry records enrollment of 15, no masking, and no separate comparator group. The intervention description specifies a total of 5 treatments over a 2-week period, including stimulation to the right TGd region and two additional sites within large-scale brain networks.

The primary outcome is change in the number of abnormal TGd parcellation connections at 9 weeks, summarized as a mean with standard deviation. Its observed result and statistical analysis are not reported in the registry record. The record also does not report the analysis plan, missing-data approach, or outcome analysis population.

For safety, the registry reports 0 serious adverse events among 10 participants at risk, 10 affected by other adverse events among 10 at risk, and 0 deaths. The reason the safety denominator differs from enrollment is not reported.