Effects of Pregnenolone on Perceived Social Isolation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Pregnenolone on Perceived Social Isolation (NCT02826577), a randomized phase 2 study. The primary outcome is EEG Results.

2. Clinical Question

The research question focused on social threat processing in people with perceived social isolation. The study description proposed behavioral paradigms addressing attention to social threat, perception of others, and emotion regulation, together with high-density electrical neuroimaging. Eye movement tracking is listed as a secondary outcome. These measures were intended to characterize responses to social information and brain activity, rather than to establish a clinical benefit.

The registry record lists enrollment of 34. Its brief summary describes a planned group size of N = 24 for each of the pregnenolone 175mg, pregnenolone 400mg, and placebo groups. The record does not explain the difference between that proposed group size and the enrollment listing, nor does it report the numbers assigned to or assessed in each group. Without analyzed outcome data, the question about group differences remains unanswered.

3. Trial Design

NCT02826577 is recorded as a phase 2, randomized, double-blind, parallel study sponsored by the University of Chicago. The registry lists the condition as perceived social isolation and gives enrollment as 34. The record describes single-dose interventions of pregnenolone 175mg, pregnenolone 400mg, and placebo. It also lists matched healthy controls with no intervention, but does not explain how those controls fit into the randomized, parallel comparison.

The brief summary describes young adults high in perceived social isolation and proposes assessments two hours after oral administration. The primary outcome, however, is described as change from baseline EEG results at 8 weeks. How the planned acute assessments relate to the primary outcome timeframe is not reported in the registry record. The listed secondary outcome is eye movement tracking. The record does not give detailed measurement procedures, assessment schedules for the secondary outcome, or the number of participants contributing to any measure.

The study is marked terminated. Its primary outcome description states that no data were collected or analyzed because the principal investigator left the institution. Consequently, the registry does not report completed group comparisons or outcome estimates. Although the brief summary describes a proposed N = 24 in each of three drug groups, the listed enrollment is 34; assignment and completion counts are not reported in the registry record. The reason for termination is stated, but other operational details, such as when recruitment stopped or whether any participants received an intervention, are not reported.

Randomization and double masking are design features intended to reduce systematic differences between groups and influence on assessment. They do not by themselves establish that allocation occurred as planned, that masking remained intact, or that outcome data were available. Those implementation details are not reported in the registry record. No statistical analysis plan or description of the procedures used to compare groups is reported.

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: No participants started the trial and received the intervention.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No data was collected or analyzed due to Principal Investigator leaving the institution.

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: No data was collected or analyzed

6. Primary Endpoint

The registry lists the primary outcome as EEG Results, measured over 8 weeks.

The primary outcome is titled EEG Results and is defined as change from baseline EEG results at 8 weeks. The description focuses on evoked brain potentials: electrical brain responses associated with a specific cognitive event or stimulus. It says that electrical activity evoked by each type of stimulus would be averaged to calculate these potentials. The unit and a specific summary parameter are not reported.

EEG can be used in research on cognitive and emotional processing because it records electrical activity over time while a participant responds to stimuli. Evoked potentials are intended to capture responses linked to particular events, rather than an undifferentiated measure of brain activity. In this study, the stated research context was processing of social threat, perception of others, and emotion regulation. Those are the study aims; the registry does not report results connecting any brain measure to a change in perceived social isolation.

As a general statistical point, a change-from-baseline outcome compares a follow-up measurement with a participant’s starting measurement. Its interpretation depends on how the measurements are defined, how changes are summarized, and how groups are compared. The record does not specify the EEG summary measure, stimulus categories, handling of repeated responses, or comparison method. Most importantly, it states that no data were collected or analyzed for the primary outcome. Thus, there is no observed change estimate or group contrast to interpret.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, double-blind, parallel design, but does not report a statistical analysis plan. It also states that the primary outcome was not collected or analyzed. The methods discussion therefore describes general principles relevant to the stated design and EEG endpoint, not procedures confirmed to have been used in this study.

What randomization contributes

In general, random allocation is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. That rationale applies when participants are allocated as planned and the groups are analyzed appropriately. The registry record does not report the allocation sequence, concealment procedures, group assignment counts, or whether randomization was completed. The design label alone cannot establish how allocation worked in practice.

A parallel design assigns participants to a group and evaluates the groups over the study period. The registry lists three drug interventions and also describes matched healthy controls without intervention. The record does not explain whether the controls were part of the randomized design or how they would enter a statistical comparison. It does not report a contrast definition or identify which groups were intended to be compared for each outcome.

What masking can and cannot establish

Double masking is intended to limit the influence of treatment knowledge on participants and study personnel. In general, masking can reduce some sources of expectation and assessment bias, but it does not remove all possible bias and does not guarantee equal follow-up or complete data. The registry record does not describe who was masked, how masking was implemented, or whether it was maintained. Since the primary outcome was not analyzed, there is no reported analysis with which to assess the consequences of masking or departures from the planned procedure.

How a change outcome is interpreted

The primary endpoint is described as change from baseline EEG results at 8 weeks. In general, a change score represents a follow-up measure relative to a starting measure. Researchers may summarize such measures at the participant level and compare group summaries, but the specific summary and model for this study are not reported in the registry record. The endpoint description says that evoked electrical activity would be averaged for each type of stimulus. It does not specify the stimulus categories, the EEG processing procedures, or the exact value used for analysis.

Evoked potentials are responses linked to a stimulus or cognitive event. In general, averaging responses can help characterize a repeatable signal, while variation across people and measurements affects the precision of a group estimate. If measurements vary substantially more than an analysis model expects, standard errors and tests based on that model may not adequately reflect uncertainty; this is one reason analysts examine distributional assumptions and model fit. No such checks or EEG analysis details are reported for this study. There are also no posted estimates from which to assess variability.

Estimates, uncertainty, and tests

In general, an effect estimate describes the size and direction of a contrast, while its standard error reflects uncertainty under the chosen analysis. A confidence interval conveys a range of values compatible with the data and method. A p-value assesses how unusual data would be under a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. These quantities are useful only when tied to a defined outcome, comparison, analysis population, and statistical model. None of these efficacy results is reported in the registry record.

The record does not specify whether any planned comparisons would have been adjusted for baseline EEG, other participant characteristics, or repeated measurements. It does not report the significance threshold for the primary analysis, a model, a method for handling multiple outcomes, or an approach to missing data. The sample-size assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are assumptions for an illustration, not a report of the trial’s statistical plan. The record does not report that these assumptions governed the study’s design or analysis.

Why planning illustrations are not trial results

Sample-size planning asks how many participants would be needed under particular assumptions about an effect, variability, allocation, and statistical method. The registry record labels its planning assumptions as illustrations based on a fraction of an observed effect. No primary outcome effect was observed or analyzed in the record, so those illustrations cannot be interpreted as empirical results or as evidence that the trial had a particular level of power. Sample size and power calculations do not replace the estimate and uncertainty from an actual analysis.

In general, post hoc power calculated from an observed estimate does not provide a useful substitute for reporting that estimate and its confidence interval. Here, the record reports no primary estimate to interpret. The planned group size in the brief summary and the listed enrollment are not enough to determine how many participants would have contributed usable EEG data. The number analyzed, the amount of missing data, and the reasons for any missing measurements are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study description includes EEG activity across types of stimuli, several behavioral research aims, and eye movement tracking as a secondary outcome. When an analysis considers multiple outcomes, stimulus categories, time points, or group contrasts, the chance of finding an apparently notable result can increase if no approach to multiplicity is specified. General approaches include defining a primary contrast in advance or adjusting inference for a family of comparisons. The registry record does not report a multiplicity strategy, a hierarchy of secondary outcomes, or how stimulus-specific analyses would have been handled.

The primary outcome is described at 8 weeks, while the brief summary also refers to assessment two hours after administration. The relationship between those timeframes is not explained. A data-analysis plan specifying which measurements and time points would support the primary comparison is not reported in the registry record. The record also does not give an analysis population, such as whether all randomized participants or only participants with available measurements would be included.

Because the registry says no primary outcome data were collected or analyzed, it is not possible to characterize missingness as ordinary incomplete follow-up within an analyzed endpoint. The record does not report whether participants were enrolled, randomized, dosed, or assessed before termination, or whether any partial data existed for secondary outcomes. The reasons and amount of missing outcome data, if any, are not reported in the registry record. There is consequently no basis for evaluating imputation, complete-case analysis, or sensitivity analyses.

The adverse-event listing gives zero at risk and zero affected for the listed groups and categories. The record does not explain the meaning of those entries in relation to exposure or collection, so they should not be treated as proof that no adverse events occurred. The methods for adverse-event monitoring and analysis are not reported.

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

The record establishes that a randomized, double-blind phase 2 study of pregnenolone in the context of perceived social isolation was registered, with a planned EEG endpoint and a listed eye movement tracking outcome. It also identifies the study as terminated and states that no primary outcome data were collected or analyzed because the principal investigator left the institution. These registry entries describe the study and the absence of an efficacy result; they do not demonstrate an effect or a lack of effect.

In particular, there is no reported estimate for change from baseline EEG results at 8 weeks. No group comparison, confidence interval, or p-value is reported for that endpoint. There is also no posted result for eye movement tracking. The registry therefore cannot support a conclusion about whether the planned pregnenolone groups differed from placebo on the listed measures, or how precisely any such difference might have been estimated.

The brief summary describes a proposed N = 24 in each of the three drug groups, and the registry lists enrollment of 34. Neither figure reveals the number of participants with analyzable data in each group. The relationship of the matched healthy controls to the randomized study is also unclear. The record does not report participant flow or the outcome population, so neither planned enrollment nor total enrollment can be used to infer an analysis denominator.

As a general principle, absence of a reported result is not evidence that the result was zero. It may reflect that an outcome was not measured, not analyzed, or not entered into the registry. In this case, the record explicitly says that primary outcome data were not collected or analyzed. That limits interpretation to the design and reporting status rather than treatment effects. The adverse-event entries likewise lack enough context to establish the presence or absence of events among exposed participants.

The research question remains statistically unresolved in the registry record. Any planning illustrations tied to an observed effect should be understood as hypothetical planning calculations, not as evidence about the observed response in this study.

12. Why This Trial Matters Statistically

This study illustrates why registered design details and analyzed results answer different questions. Randomization, masking, and a defined EEG endpoint describe how investigators planned to investigate a question. They do not provide an estimate of the intervention contrast. The registry record marks the study terminated and states that the primary outcome was not collected or analyzed, so the planned design cannot be translated into a measured effect.

It also highlights the importance of aligning the endpoint definition, assessment schedule, and analysis plan. The primary outcome is change from baseline EEG results at 8 weeks, while the brief summary describes study assessments two hours after administration. The registry does not explain how these timeframes relate. Without a clearly reported endpoint and analysis schedule, readers cannot know which measurements would have contributed to the primary comparison even if results were available.

Enrollment and intended group size also have distinct meanings. The record lists enrollment of 34 and describes N = 24 for each drug group in its brief summary, but does not report allocation or analysis counts. The difference cannot be resolved from the registry information. This is a reminder that a total enrollment entry is not a substitute for participant flow or outcome-specific denominators.

Finally, planning calculations rely on assumptions and are not evidence of precision in an unreported analysis. The record has no observed primary effect to support interpretation of an effect-based planning illustration. Statistically, the central limitation is not a small or uncertain estimate but the absence of an analyzed estimate altogether. Clear reporting of whether outcomes were collected, why analyses were not completed, and which participants contributed data is essential for readers to distinguish an inconclusive result from a result that was never obtained.

13. 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 central trial-specific limitation is explicit: the primary outcome description says that no data were collected or analyzed because the principal investigator left the institution. There is therefore no primary endpoint estimate to interpret and no statistical comparison to evaluate. The terminated status reinforces that the planned study did not yield a reported primary analysis, but the registry does not provide further details about when or how termination affected recruitment, treatment, or follow-up.

Several design details remain unclear in the registry record. The brief summary describes N = 24 for each pregnenolone and placebo group, while enrollment is listed as 34. Assignment counts, participant flow, and the numbers completing assessments are not reported. Matched healthy controls are described as receiving no intervention, but their role relative to the randomized parallel groups is not explained. The eligibility criteria beyond young adults with high perceived social isolation are not reported.

The primary outcome definition provides a broad description of evoked brain potentials but no unit or specific parameter. It describes averaging activity by stimulus type without reporting the stimulus categories, EEG processing choices, or planned statistical model. The brief summary refers to assessment two hours after administration, whereas the primary endpoint timeframe is 8 weeks; the relation between these is not reported. The registry also does not provide the analysis plan, multiplicity handling, missing-data approach, or analysis populations.

Eye movement tracking is listed as a secondary outcome, but no results are reported. Adverse-event entries list zero at risk and affected, yet the record does not explain collection or exposure context. These limitations mean the registry record supports description of the intended research question and its status, but not an assessment of efficacy, precision, or safety findings.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Effects of Pregnenolone on Perceived Social Isolation — NCT02826577.
• Registry record last updated 2024-05-16; status last verified 2024-05.
• Results first posted 2024-05-16.
• 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.

17. Record Summary

NCT02826577, titled Effects of Pregnenolone on Perceived Social Isolation, is listed as a phase 2 randomized, double-blind, parallel study sponsored by the University of Chicago. The registry lists perceived social isolation as the condition and enrollment of 34. The study is marked terminated.

The planned interventions were single doses of pregnenolone 175mg, pregnenolone 400mg, and placebo. The brief summary describes young adults with high perceived social isolation and proposed assessments after administration. Matched healthy controls with no intervention are also described, but their role in the randomized comparison is not reported. Eye movement tracking is listed as a secondary outcome.

The primary outcome was change from baseline EEG results at 8 weeks, measured as evoked brain potentials. The registry record states that no primary outcome data were collected or analyzed because the principal investigator left the institution. It does not report efficacy estimates, statistical tests, or participant analysis counts.