Flexibility, Alcohol Misuse, and Excitation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Flexibility, Alcohol Misuse, and Excitation (NCT06634771), a randomized na study. The primary outcome is Change in Proportion of Errors.

2. Clinical Question

The registry frames the behavioral question around habitual action selection: after a previously correct response becomes incorrect, do participants continue making that response? The primary measure focuses on perseverative errors for a devalued familiar set. The study also planned to examine biological and functional-connectivity outcomes, but those measures do not replace the primary behavioral question.

Interpretation must account for the early termination and incomplete enrollment across the planned arms. The reported group summaries describe only the participants and arms with posted outcome values; they cannot establish whether stimulation changed the outcome or whether any change differed by alcohol-use history.

3. Trial Design

NCT06634771, titled “Flexibility, Alcohol Misuse, and Excitation,” was a randomized, triple-masked, parallel-group study sponsored by the University of North Carolina, Chapel Hill. Its phase is listed as NA. The registry lists enrollment of 7 and a terminated status. The recorded start date is 2024-07-18 and the primary completion date is 2025-01-24.

The study compared 10 Hz active tACS with sham tACS. The planned groups separated controls, current high-risk drinkers, and current high-risk drinkers with adolescent binge drinking. The registry states that termination occurred before enrollment into the active current-high-risk-drinker arm, the active arm for current high-risk drinkers with adolescent binge drinking, or the sham arm for that latter group. The results therefore do not cover every planned population and treatment combination.

Participants were to complete behavioral training, an MRI session, and a stimulation session during behavioral testing with EEG recordings before and after stimulation. The study description also includes a repeat MRI session and finger-prick blood samples at the first and last visits. These procedures indicate that the research aimed to connect behavior with neural and biological measures; they do not establish that every planned procedure or measure was completed for every enrolled participant.

The posted primary outcome is continuous: the mean change in the proportion of perseverative errors. Results are reported for the two control groups and the sham group among current high-risk drinkers. The active current-high-risk-drinker group and both adolescent-binge-drinking groups have no participants with outcome values. The registry reports no posted analyses. Detailed information about the randomization procedure, allocation concealment, masking implementation, and analysis plan is 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

Analysis population for the primary outcome, as defined in the registry: Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms.

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.

Population: Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Change in Proportion of Errors, measured over Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after.

The primary endpoint is change in the proportion of errors that were perseverative during the reversal test in the HABIT task. Participants first learn stimulus-response pairings. During the reversal test, the correct response for a familiar set changes, so a previously correct button press is no longer correct. The endpoint is the proportion of errors for the devalued familiar set that consist of repeating that previously correct response.

This measure is used to represent persistence in a learned response after the task rules change. It focuses on a specific form of error rather than counting all errors as equivalent. That distinction is relevant to the study’s question about habitual action selection and behavioral flexibility. The registry describes the outcome as a mean change from pre-stimulation assessment to post-stimulation assessment, with the pre-stimulation session occurring up to 2 weeks before and the post-stimulation assessment immediately after stimulation.

The reported group values are changes in the measure, not raw post-stimulation scores. The registry gives the unit as proportion of perseverative errors and the summary statistic as a mean with standard deviation. It does not state in the available record how the change was signed, such as whether it was calculated as post-stimulation minus pre-stimulation or the reverse. Therefore, the signs should be read as the posted changes without assigning a direction of improvement or worsening.

The endpoint is behavioral. Although the study also sought to examine excitability and other neural or biological measures, those measures are distinct from the primary endpoint and do not determine the interpretation of its group summaries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous and is summarized as a mean change with a standard deviation. A mean describes the average observed change within a group. A standard deviation describes how dispersed individual observations are around that group mean. It is not a confidence interval and does not, by itself, quantify the precision of the mean. In the posted results, standard deviations appear for the two control groups but not for the high-risk-drinker sham group.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimate under a stated statistical model and procedure. It is useful because an estimate alone does not show how precisely the data locate the underlying quantity. The registry does not report confidence intervals for the primary endpoint. With so few observations in the groups that have values, uncertainty would be important to communicate, but an interval cannot be recovered from the information posted without making additional assumptions or calculations.

Why is a treatment comparison different from group summaries?

A treatment comparison targets the contrast between outcomes under active and sham stimulation in a defined population. Separate group means are descriptive summaries; they are not themselves an inferential comparison. A formal analysis would need to specify how the outcome is modeled, which participants are included, how the treatment groups are compared, and how uncertainty is quantified. The registry does not post an analysis for the primary endpoint, and its record indicates that the two-arm continuous-endpoint comparison was skipped because values were missing or not estimable. The summaries therefore should not be treated as a tested treatment effect.

Randomization is intended to support fair comparisons by assigning participants to groups according to a random process. The registry identifies the study as randomized, but details of the sequence generation, concealment, and implementation are not reported in the registry record. Randomization also does not guarantee balanced groups in a very small study. The posted group sizes and missing planned arms make it especially important not to assume that descriptive differences represent causal effects.

How should the sample-size illustrations be read?

General sample-size calculations estimate how many participants might be needed under specified assumptions to detect an effect with a chosen error rate and allocation scheme. They are planning illustrations, not observed power and not proof that a study was adequately powered. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The illustrations are not the trial’s own design justification. The record does not report the protocol’s sample-size justification.

Because the two-arm comparison for this continuous endpoint is not estimable from the posted values, an observed effect cannot serve as a sound basis for a meaningful planning illustration for that comparison. No sample-size output should be interpreted as an observed property of the trial or as evidence about whether the intervention effect is real. The registry does not report a protocol-based target or the assumptions used when the study was designed.

Why can a proportion outcome require care?

In general, a proportion is bounded and its distribution can depend on the number of trials or opportunities contributing to it. A mean and standard deviation may not fully describe the shape of the data, particularly when observations are concentrated near a boundary or have unequal precision. Over-dispersion occurs when variability exceeds what a chosen model assumes; if present, it can make model-based uncertainty estimates too small unless the model accounts for it. These are general considerations, not claims about the distribution in this trial. The registry does not report participant-level task counts, a distributional assessment, or a model specification for the primary endpoint.

Repeated measurement also matters conceptually because the endpoint is a change from pre-stimulation to post-stimulation. An analysis could use change scores or model measurements over time, but the registry does not state which approach was used. The posted group summaries alone do not reveal whether baseline values differed or how such differences were handled. The registry record also does not report adjustments for covariates, treatment-by-population interactions, or other modeling choices.

Finally, the number of planned outcomes raises a general issue of multiplicity: testing many outcomes or comparisons can increase the chance of at least one apparently notable result. The registry lists 8 outcome measures, including 6 secondary outcomes, but does not report a multiplicity procedure or a statistical analysis plan. No conclusions about statistical significance or confirmatory status can be drawn from outcome counts alone. The absence of posted analyses means there are no reported inferential results to interpret across these outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and identifies 6 secondary outcomes, including changes in inflammatory markers and functional connectivity. It reports no analyses. A statistical analysis plan, including any hierarchy among outcomes or comparisons, is not reported in the registry record. It is also not reported whether the investigators planned to adjust for multiple testing, designate some outcomes as exploratory, or control a family-wise error rate. The presence of several outcomes does not show that each was tested or that any result was statistically significant.

Missingness is a direct concern for the primary endpoint because several planned groups have no participants with outcome values. The registry states that the study terminated before enrollment into the active current-high-risk-drinker group and both adolescent-binge-drinking groups. The listed results consequently do not cover all planned comparisons. The record does not report whether any enrolled participants had missing primary measurements, why any individual measurement might be missing, or how missing observations were handled in an analysis.

Analysis populations are also not described in sufficient detail to determine whether results were intended to include all randomized participants, only participants with available outcome data, or another defined set. The record does not report exclusions after randomization, adherence criteria, or a treatment of protocol deviations. No imputation method or sensitivity analysis for missing data is reported. These absences prevent assessment of whether the posted summaries represent a prespecified analysis population or how robust an analysis would be to incomplete observations.

Because there are no posted analyses, multiplicity and missing-data methods cannot be evaluated through reported estimates. The absence of those details should be treated as uncertainty about the analysis, not evidence that a particular method was or was not used outside the registry record.

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.

The registry separates participants at risk from participants affected by serious and other adverse events. In the active control group, 3 participants were listed as at risk for serious adverse events and 0 as affected; for other adverse events, 3 were at risk and 0 were affected. In the sham control group, the corresponding counts are 3 at risk and 0 affected for serious events, and 3 at risk and 0 affected for other events. In the current-high-risk-drinker sham group, 1 participant was listed at risk and 0 affected for both categories.

The active current-high-risk-drinker group and both adolescent-binge-drinking groups have 0 participants listed at risk. Those rows do not provide meaningful exposure-based reassurance about safety in those populations, because no participants were enrolled in those arms. The record lists 0 deaths, and no serious adverse-event terms are listed.

These figures describe the registry’s posted counts; they do not establish that an intervention is risk-free. The small number of participants and the lack of enrollment in several planned groups mean that uncommon events or risks in those populations cannot be assessed from these results. The registry does not provide additional event narratives or a detailed account of monitoring in the information reported.

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

The posted results document outcome summaries for a limited set of enrolled groups in a study that was terminated. They show a mean change of 0.090 in the active control group and -0.030 in the sham control group, each with 3 participants, and a mean change of 0.057 in the current-high-risk-drinker sham group, with 1 participant. They also show that no primary outcome values are posted for the active current-high-risk-drinker group or either planned group for current high-risk drinkers with adolescent binge drinking.

Those figures do not answer whether active tACS changes perseverative errors relative to sham. The registry posts no inferential comparison, confidence interval, or p-value for the primary endpoint. The group summaries do not establish that a difference is caused by stimulation, nor do they establish whether response varies with alcohol-use history. The study’s stated interest in prefrontal excitability, neural connectivity, and biological measures likewise cannot be resolved from the primary outcome summaries.

The results also do not show that the intervention has no effect. A lack of an estimable comparison is different from a precise estimate centered on no effect. The small groups, absent values in planned arms, and missing inferential results leave substantial uncertainty. The posted summaries should be read as descriptive observations from the enrolled participants, not as a conclusive test of the study’s research questions.

More broadly, the registry record does not report the detailed statistical plan, methods for missing data, or an explanation of the termination. Those omissions limit assessment of how the investigators intended to analyze the outcomes and why the trial ended. The record supports a cautious account of what was observed, but not a general claim about stimulation effects in controls or people at higher risk of alcohol use.

13. Why This Trial Matters Statistically

This trial illustrates how study design and enrollment determine what statistical questions can be answered. The research planned comparisons across control participants, current high-risk drinkers, and current high-risk drinkers with adolescent binge drinking. Termination before enrollment into several planned arms left those comparisons without outcome data. A study can be randomized and masked yet still yield no estimable treatment contrast for a population that was not enrolled.

The record also distinguishes descriptive results from an inferential analysis. A mean and standard deviation describe the observations in a group; they do not, on their own, quantify the active-versus-sham effect or its uncertainty. This distinction is particularly important when group sizes are small and one group has only a single participant, for whom no standard deviation is reported. The available summaries should not be made to carry more inferential weight than they can support.

The endpoint itself raises useful measurement questions. It is a proportion of task errors with a specific behavioral definition, measured as change across sessions. Interpreting such a measure requires clarity about the sign of the change, how the task observations contribute to the proportion, and how repeated measurements are handled. The registry record does not provide all of those analytical details.

Finally, the study lists multiple behavioral, biological, and connectivity outcomes but posts no analyses. This makes transparent reporting of outcome priorities, missing-data methods, and multiplicity procedures especially relevant. The record is a useful example of why results should be read alongside enrollment status and analysis availability: counts and means can be informative descriptions while remaining insufficient to answer the causal or mechanistic questions that motivated a trial.

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 that the trial was terminated after enrollment of 7 participants, before participants entered several planned arms. The posted results therefore do not represent the full set of intended populations and comparisons. In particular, no outcome values are reported for active tACS among current high-risk drinkers or for either arm among current high-risk drinkers with adolescent binge drinking.

Even among groups with primary outcome values, the sample is very small. The two control groups each have 3 participants, while the current-high-risk-drinker sham group has 1 participant. Its standard deviation is not reported. These data provide limited information about variability and do not support a stable estimate of a treatment contrast. The registry reports no confidence intervals or inferential analyses for the endpoint.

The record does not report the detailed statistical analysis plan, the treatment of missing observations, the analysis populations, or whether any outcome or participant was excluded. It also does not explain the reason for termination in the information available. The sign convention for the change measure is not stated in the endpoint description, which limits interpretation of whether positive or negative changes correspond to a particular behavioral direction.

Although the study was registered as randomized and triple-masked, the procedures for randomization and masking are not described in detail in the registry record. The record lists several secondary biological and functional-connectivity outcomes, but no analyses for them are posted. These limitations mean that neither the primary treatment question nor the broader mechanistic questions can be resolved from the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Flexibility, Alcohol Misuse, and Excitation — NCT06634771.
• Registry record last updated 2026-03-27; status last verified 2026-01.
• Results first posted 2026-03-27.
• 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.

18. Record Summary

NCT06634771 was a randomized, triple-masked, parallel-group study of 10 Hz active tACS versus sham tACS. It was sponsored by the University of North Carolina, Chapel Hill, and is listed as terminated. Enrollment was 7; the recorded start date was 2024-07-18 and the primary completion date was 2025-01-24.

The primary outcome was change in the proportion of perseverative errors during the HABIT reversal test. The registry posts descriptive values for both control groups and the sham group among current high-risk drinkers. Several planned arms have no enrolled participants with outcome values. No analyses are posted, and an active-versus-sham comparison for the continuous primary endpoint is not estimable from the registry results.

The posted adverse-event counts include no affected participants and no deaths in the groups with participants at risk. Because enrollment was limited and planned arms were not populated, these safety counts and outcome summaries should be interpreted as limited descriptive evidence rather than a comprehensive assessment of efficacy or safety.