Investigation of Low-intensity Focused Ultrasound Parameters: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Low-intensity Focused Ultrasound Parameters (NCT05134233), a na na study. The primary outcome is Waveforms.

2. Clinical Question

3. Trial Design

The registry lists “Investigation of Low-intensity Focused Ultrasound Parameters” as a completed study sponsored by Virginia Polytechnic Institute and State University. The study began on 2022-01-14, and the primary completion date is 2024-03-11. Enrollment is recorded as 23. Phase and allocation are listed as NA; masking is listed as none; and the design model is single group. These features identify an investigation of stimulation parameters, rather than a randomized comparison of separate intervention and control groups.

The intervention is a device, low-intensity focused ultrasound. The registry description says participants underwent structural imaging, fMRI and CT, used to align LIFU and transcranial magnetic stimulation (TMS) devices. The stated purpose of the stimulation procedures was to temporarily change brain activity. EMG recorded hand muscle contractions. The arm is called Parameter Trials, with approximately 36 parameter combinations tested per study session and 6 sessions expected. Responses were recorded using TMS and EMG.

The primary outcome was measured throughout study participation, described as an average of 4 weeks per participant. This repeated testing context matters: multiple measurements or parameter conditions within a participant are not automatically independent observations. The registry entry does not report the detailed sequence of settings, the number of usable measurements, or how repeated observations were handled statistically.

The record identifies one participant data set with artifacts that could not be removed while leaving usable MEP data. It does not specify how this affected the analysis population or the handling of other missing or unusable observations. No separate control arm, randomization scheme, or masking procedure is described. Although the status is completed, numerical outcome analyses 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One participant data set had artifacts that could not be removed while leaving usable MEP data.

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 Waveforms, measured over Outcome measured throughout study participation - an average of 4 weeks per participant..

The primary outcome is “Waveforms,” measured as a mean in percentage of baseline MEP mV. The description says waveform peak changes were to be observed for each variable LIFU application. MEP refers to the motor-evoked-potential measurement used in the study’s response assessment, while EMG records muscle activity. The listed unit expresses the waveform measure relative to a baseline MEP value; it is not a direct clinical outcome such as improvement in symptoms or function.

Continuous waveform measurements can help describe the magnitude and variation of a physiological response across stimulation settings. A mean gives a measure of the central response, while the listed standard deviation describes spread among the observations included in that summary. Neither measure alone identifies whether a setting caused a change. Interpretation also depends on the number and quality of usable observations, the baseline definition, repeated measurements within participants, and the statistical method used to compare parameter conditions.

The outcome timeframe is throughout study participation, described as an average of 4 weeks per participant. The record does not report numerical means, standard deviations, confidence intervals, or an analysis comparing settings. It also does not describe a clinically meaningful threshold for waveform change. Consequently, the endpoint definition explains what was intended to be measured, but the registry record does not provide the numerical results needed to estimate the observed response or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how measurements are converted into estimates and how much uncertainty accompanies those estimates. The registry record identifies the primary outcome as a continuous mean with standard deviation, but it reports no outcome analyses. The methods below are general explanations of what would matter for this type of parameter study; they are not a description of an analysis confirmed by the registry.

What does a mean describe?

For a continuous measure, a mean summarizes the center of a set of observations. In this study, the intended observations are waveform measurements expressed in percentage of baseline MEP mV. A mean can be useful for describing the average response at a parameter condition, but it can conceal variation among participants and conditions. It also depends on which observations are included and on how repeated measurements are summarized.

The standard deviation describes how dispersed individual observations are around their mean. A larger spread can arise from genuine differences between participants, variation across repeated measurements, measurement noise, or a mixture of these sources. A standard deviation is not the same as the uncertainty in the mean. That uncertainty also depends on the effective amount of independent information and on the analysis structure. The registry reports the intended dispersion statistic but provides no numerical standard deviation.

Why does the repeated-measures structure matter?

The registry describes parameter combinations tested over sessions, with responses recorded using TMS and EMG. When one participant contributes observations under multiple conditions, those measurements are likely to share participant-specific features. General statistical practice accounts for that dependence, for example by using a model that represents within-participant correlation or by defining a justified participant-level summary. The record does not say which method, if any, was used.

Ignoring dependence can affect standard errors and confidence intervals because the number of measurements is not necessarily the same as the amount of independent information. Conversely, an analysis that appropriately uses repeated observations can characterize within-participant patterns, provided its assumptions and data structure are suitable. The registry does not provide the observation-level structure, model specification, or diagnostics needed to assess these issues.

What would an estimate and confidence interval contribute?

An estimate describes the effect or response targeted by an analysis. A confidence interval conveys the uncertainty around that estimate under the model and its assumptions. A narrow interval indicates greater statistical precision for the specified estimand than a wide interval, but neither interval width nor statistical significance alone determines clinical importance. The registry record reports no numerical estimate or confidence interval for the waveform outcome, and it identifies no threshold for a meaningful waveform change.

A p-value, if used, would address compatibility between the observed data and a specified null model, given the analysis assumptions. It would not measure the probability that the null hypothesis is true, nor would it describe the size of a response. No p-value or hypothesis test is reported in the registry record. The primary analysis plan and the choice of contrasts among parameter settings are also not reported.

How should multiplicity be considered?

Testing multiple parameter combinations can raise a multiplicity issue if many comparisons are examined and only selected findings are emphasized. General approaches include identifying a primary contrast in advance, controlling an error rate across a defined family of tests, or clearly labeling exploratory comparisons. The registry describes approximately 36 parameter combinations per study session and 6 expected sessions, but it does not report a multiplicity strategy or the number of analyses performed. Zero analyses are listed, so no inferential results are available to evaluate for multiplicity.

What do the planning illustrations mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record specifies that non-time-to-event planning values are participants per arm. These are assumptions for planning calculations, not a report of the trial’s design rationale and not observed power.

Those assumptions describe a two-arm framework, whereas this study is listed as single group with no randomized comparator. A two-arm planning illustration therefore should not be read as the actual design or as evidence that the study was powered for its parameter comparisons. The protocol’s sample-size justification and the method used to choose the study enrollment are not reported in the registry record. No numerical planning results are needed to distinguish a planning calculation from an observed analysis.

Finally, the study notes that artifacts prevented one participant data set from retaining usable MEP data. General analysis practice would describe quality-control rules, exclusions, missingness, and any sensitivity analyses. Those details are not reported in the registry record. Without a stated analysis population and method, the reported endpoint definition alone cannot establish how the collected measurements were summarized.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a prespecified hierarchy of outcomes, or a strategy for handling multiplicity. This matters because the study description involves multiple stimulation parameter combinations. If multiple contrasts are tested, the interpretation of nominal statistical tests can depend on how the comparisons were selected and whether any adjustment or exploratory labeling was used. The registry record does not identify the comparisons or report inferential results.

Missing-data information is limited. The primary outcome description notes that one participant data set had artifacts that could not be removed while leaving usable MEP data. The record does not explain whether that data set was excluded from all analyses, whether any portion remained usable for another purpose, or whether other measurements were missing or unusable. The reasons for missingness beyond the stated artifacts, and any imputation or sensitivity analysis, are not reported in the registry record.

The analysis population is also not defined. Enrollment is listed as 23, but the registry does not state the number contributing usable primary-outcome data or the criteria for inclusion in an analysis. The single-group design does not involve a reported intention-to-treat comparison, and no alternative analysis population is specified. These gaps prevent assessment of whether the analyzed observations represent all enrolled participants or a selected subset. They also limit assessment of the potential effects of missing measurements on estimates.

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 5% reporting threshold.

The registry lists 23 participants at risk for serious adverse events and records 0 affected, with no serious adverse-event terms listed. It also lists 23 at risk for other adverse events and records 0 affected. Deaths are recorded as 0. These are the event figures posted for the Parameter Trials group.

A zero count means that the registry reports no affected participants in the listed categories; it does not establish that the procedure has no risk. Safety interpretation depends on the scope and duration of monitoring, how events were defined and collected, and whether all events were reported. The registry entry does not provide detailed event definitions, monitoring procedures, or a narrative explaining the zero counts. The outcome timeframe describes the primary waveform measure, not necessarily the full safety-monitoring period.

These safety figures should also be kept separate from the primary waveform endpoint. They describe adverse-event reporting, not the size or direction of a physiological response. The posted safety counts alone do not support broader conclusions about safety beyond the categories and reporting recorded in the registry.

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

The study addresses a statistical and measurement question: how waveform responses recorded during LIFU parameter testing are described across variable stimulation applications. It is not listed as a randomized trial with a control group. The registry therefore does not support a causal comparison of LIFU with a separate comparator, and the primary outcome is a physiological measurement rather than a reported clinical outcome.

The registry record identifies a mean waveform measure, its unit, a standard deviation as the intended dispersion measure, and a measurement period described as an average of 4 weeks per participant. It also describes imaging, device alignment, TMS and EMG measurements, parameter combinations, and an artifact-related data limitation. These registry entries clarify what the study set out to measure and some of the conditions under which observations were collected.

However, the record reports zero analyses and no numerical primary-outcome results. It therefore does not show the observed mean response, variation, uncertainty, or differences among settings. It is not possible from the registry record to determine whether waveform values changed, how large any change was, or whether observed patterns were statistically distinguishable from variation. The completed status does not fill this results gap.

Nor can a waveform measurement alone establish a clinical benefit or harm. The registry’s summary mentions possible areas of future interest, but no clinical effectiveness endpoint is reported in the primary outcome information. The reported event counts describe registry safety reporting and should not be treated as proof of no risk. Overall, the record provides a design and endpoint description, but not the analysis results needed to draw conclusions about response magnitude, precision, or clinical relevance.

13. Why This Trial Matters Statistically

Parameter studies can be statistically challenging because they may involve many related measurements rather than a single observation per participant. Describing the unit of analysis, the dependence among repeated observations, and the planned contrasts is important for interpreting both estimates and uncertainty. This study’s registry description makes the repeated parameter-testing context visible, but does not report the analysis approach or numerical results.

The distinction between a physiological endpoint and a clinical outcome is also important. Waveform measures can characterize a recorded response, but the meaning of a change depends on the endpoint’s interpretation and its relationship to outcomes that matter to participants. The registry defines the waveform measure and its scale, but does not report a clinically meaningful threshold or a clinical outcome analysis.

Data quality can affect the analysis population and precision. The record explicitly notes one participant data set with artifacts that could not be removed while retaining usable MEP data. Reporting how such observations were handled, alongside the number of usable measurements and the method for repeated observations, would help readers judge the robustness of estimates. Those details are not reported in the registry entry.

Finally, planning calculations and completed-study results answer different questions. The assumptions listed for sample-size illustrations do not establish the trial’s design justification or its observed statistical power. For this single-group parameter investigation, separating planning assumptions from empirical results is particularly important. The registry’s lack of outcome analyses makes that distinction central: the record defines a potentially informative measurement question, but does not provide results with which to quantify the response.

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 statistical interpretation is the absence of numerical outcome analyses in the registry record. Although the primary endpoint and its intended summary statistics are identified, the record does not report means, standard deviations, estimates, confidence intervals, or tests. The size and precision of waveform responses therefore cannot be evaluated.

The study is listed as single group, with allocation NA and no masking. No separate randomized comparator is described. This design is suited to investigating parameter responses as described in the record, but it does not provide a like-for-like controlled comparison from which to estimate a treatment contrast. The record also does not specify the order of parameter conditions or whether order effects were considered.

Approximately 36 parameter combinations per session and 6 expected sessions are described, but the number completed and the number of usable observations are not reported. The method for handling within-participant repeated measurements is not reported, nor are the planned contrasts or multiplicity procedures. These omissions limit evaluation of statistical assumptions and uncertainty.

The record notes artifacts in one participant data set that could not be removed while leaving usable MEP data. It does not detail the impact on analysis inclusion, other missing measurements, or sensitivity analyses. Eligibility criteria, participant characteristics, and a protocol-based sample-size justification are also not reported in the registry record. These limitations mean the available entry is more informative about intended procedures than about the representativeness, robustness, or inferential strength of any findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigation of Low-intensity Focused Ultrasound Parameters — NCT05134233.
• Registry record last updated 2025-01-23; status last verified 2024-12.
• Results first posted 2025-01-23.
• 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

NCT05134233 is a completed, single-group device study titled “Investigation of Low-intensity Focused Ultrasound Parameters,” sponsored by Virginia Polytechnic Institute and State University. Enrollment is listed as 23. The study description covers imaging and alignment of LIFU and TMS devices, parameter testing, and EMG recording of hand muscle contractions.

The primary outcome is Waveforms, a continuous mean measured in percentage of baseline MEP mV, with standard deviation listed as the dispersion measure. The timeframe is throughout study participation, described as an average of 4 weeks per participant. The registry notes artifacts in one participant data set that prevented retaining usable MEP data. It lists no primary-outcome analyses, and numerical results are not reported in the registry record.