Napping, Sleep, Cognitive Decline and Risk of Alzheimer's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Napping, Sleep, Cognitive Decline and Risk of Alzheimer's Disease (NCT03256539), a randomized na study. The primary outcome is Number of Participants Enrolled to the Study.

2. Clinical Question

In statistical terms, the central registered question was whether participants could be enrolled into this pilot study, rather than whether a treatment effect on cognition or sleep could be established. The registry record lists secondary outcomes for actigraphy-assessed sleep and cognitive function assessed by a standard neurocognitive battery, but it does not report results for those outcomes.

3. Trial Design

The registry record identifies NCT03256539 as a randomized, double-masked, parallel-group study sponsored by the University of California, San Francisco. The phase is listed as NA. The study compared a behavioral sleep intervention with a behavioral placebo intervention. In a parallel-group design, participants are assigned to one study arm and the arms are followed as separate groups; this is a general description of the design label, not a claim about the details of implementation.

The record lists enrollment as 15. The posted arm results give a value of 8 for the Sleep Intervention and 7 for the Placebo Intervention. Those are arm-level enrollment counts; they do not provide information about participant characteristics, adherence, or completion. The primary outcome timeframe is up to 24 weeks following study initiation.

The recorded start date is 2021-08-12, the primary completion date is 2024-01-31, and the status is TERMINATED. The reason for termination and whether the recorded dates represent actual rather than planned milestones are not reported in the registry record. The brief description says the study aimed to pilot test a program intended to improve cognition through improvement of the 24-hour sleep-wake cycle, and to explore preliminary effects on sleep, napping, and cognition.

Randomization describes how assignment is intended to reduce systematic differences between groups, while masking is intended to limit the influence of knowledge of assignment. The registry record identifies the study as double-masked but does not say which people were masked or how masking was maintained. The randomization procedure, allocation concealment, and detailed study schedule 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:

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 Number of Participants Enrolled to the Study, measured over Up to 24 weeks following study initiation.

The primary endpoint is the number of participants enrolled in the study, measured in participants. Its stated timeframe is up to 24 weeks following study initiation. The posted arm values are 8 for the Sleep Intervention and 7 for the Placebo Intervention. This endpoint is a recruitment count: it records enrollment, rather than a change in sleep, napping, cognition, or Alzheimer’s disease status.

In a pilot study, an enrollment endpoint can describe whether recruitment occurred and provide a practical measure relevant to feasibility. That is a general explanation of the role such an endpoint can serve; the registry record does not report a recruitment target, a prespecified threshold for feasibility, or a formal criterion for interpreting the enrollment count.

Enrollment alone cannot establish whether participants completed treatment, followed the intervention, or posted outcome measurements. It also cannot estimate an intervention effect on sleep or cognition. Those questions would require results for relevant outcomes and an analysis that compares the groups. Such a comparison is not reported for the primary endpoint in the registry record. The record lists actigraphy-assessed sleep and neurocognitive function as secondary outcomes, but does not provide their results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design is randomized, double-masked, and parallel-group. Randomization is a method for assigning participants to study arms using chance. In general, its purpose is to reduce systematic differences in participant characteristics between groups, although random assignment does not guarantee that groups will be identical, especially in a pilot study. The registry record does not report the randomization sequence method, allocation concealment, or procedures used to implement assignment.

Masking means that some people involved in a study are kept unaware of treatment assignment. In general, masking can reduce the risk that expectations influence care, measurement, or interpretation. The record labels the study double-masked, but does not identify which participants, researchers, assessors, or other personnel were masked. It also does not report whether masking was assessed or maintained. The parallel-group label indicates that the arms were treated as separate groups rather than as a crossover comparison; details of the schedule are not reported.

The primary endpoint is the number of participants enrolled, a count. A count records how many events of a specified kind occur, here enrollment. The arm values are 8 and 7. The registry also states that a two-arm comparison was not estimable for a binary endpoint. A binary outcome generally classifies each participant into one of two categories, such as whether an event occurred. The record does not explain why the comparison note uses a binary classification when the primary outcome title and unit describe an enrollment count. That distinction matters because the analysis method depends on how an endpoint is defined and recorded.

No effect estimate or inferential analysis for the primary comparison is reported. General methods for comparing groups depend on the outcome scale, study design, and assumptions about the observations. For example, a count analysis may need to account for how variable counts are relative to their average; over-dispersion is the general situation in which count variability exceeds what a simpler model expects. The registry record does not report a count model, a binary model, an adjustment strategy, or any other statistical model. It would therefore be inappropriate to infer which method was planned or to recreate a sponsor analysis.

A confidence interval is a general way to express uncertainty around an estimated effect. Its width depends on the amount and variability of the data and on the analysis assumptions. A p-value, in general, describes how incompatible observed data are with a specified null model, under that model’s assumptions. Neither a confidence interval nor a p-value for an arm comparison is reported in the registry record. Because the comparison is listed as not estimable, the posted arm counts should not be converted into an unadjusted effect or treated as a significance test.

The registry record describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed trial findings. They do not represent the trial’s original design or its observed power. The record does not report the trial’s own sample-size justification, and no planning result should be interpreted as proof that an analysis had a particular probability of detecting an effect.

Planning calculations based on a fraction of an observed effect are conditional on that chosen effect size and the assumptions of the calculation. In general, an observed effect from a small pilot can be imprecise, and using it as a planning input does not remove that uncertainty. Equal allocation and a normal approximation are assumptions in the planning description, not evidence about how participants were actually allocated or about the behavior of any outcome data. The registry does not report an interim-analysis plan, stopping boundaries, or a detailed statistical analysis plan.

Outcome timing and missingness also affect interpretation. The primary endpoint has a timeframe of up to 24 weeks following study initiation, but the record does not specify when each participant was enrolled or how the timeframe was applied to individuals. It does not report whether enrollment counts were checked against another source, how incomplete records were handled, or how missing outcome assessments would be treated. These omissions limit what can be learned about the construction of the posted results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Sleep Intervention", "Placebo Intervention")
n      <- c(8, 7)
events <- c(8, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Sleep Intervention  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  Placebo Intervention  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and identifies two secondary outcomes: sleep assessed by actigraphy and cognitive function assessed by a standard neurocognitive battery. It does not report results for those secondary outcomes. It also lists zero analyses. A multiplicity plan describing how to interpret several outcome tests together is not reported in the registry record.

As a general statistical issue, testing several outcomes can increase the chance of observing an apparently unusual result even when no real effect exists. Researchers may address that issue by identifying a primary outcome, controlling error rates, or describing outcomes as exploratory. The study description does identify enrollment as primary and describes sleep and cognition effects as preliminary areas of exploration, but a formal testing hierarchy or adjustment method is not reported in the registry record. No multiplicity adjustment should be assumed.

Missing-data methods and the amount of missing outcome data are not reported in the registry record. The record does not state how incomplete observations, withdrawals, or participants without follow-up measurements were handled. An analysis population, such as an intention-to-treat or per-protocol population, is also not reported. The enrollment counts do not establish how many participants contributed to any secondary outcome analysis, and no such analysis results are posted.

These gaps do not show that data were missing or that a particular analysis population was used. They mean the registry record does not describe those matters. Without outcome-level data, analysis populations, and missing-data procedures, the robustness of any treatment comparison cannot be assessed.

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 posted safety figures record zero serious adverse events in the Sleep Intervention group, with 8 at risk, and zero in the Placebo Intervention group, with 7 at risk. The figures also record zero other adverse events in each group, with 8 and 7 at risk respectively, and zero deaths in each group. These are the safety counts reported in the registry record.

A zero count means no events of that category were recorded in the posted figures for the stated group. In general, observing no events does not establish that an event is impossible or that the risk is absent. Safety estimates can be uncertain when few participants are observed, and the record does not provide confidence intervals or a comparative safety analysis.

The registry record does not report the adverse-event collection period, definitions, severity grading rules, relatedness assessments, or the method used to collect events. It also does not describe safety monitoring procedures. These limitations matter because event counts depend on how events are defined and how completely they are collected. The figures should be read as recorded counts, not as proof that either intervention is free of risk.

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

The results establish that the registry record posts enrollment counts of 8 for the Sleep Intervention arm and 7 for the Placebo Intervention arm. They do not provide an estimable statistical comparison for the primary endpoint. The record also identifies secondary outcomes related to sleep and cognition but does not report their results. As a result, the posted information cannot establish whether the intervention changed sleep, napping, or cognitive function.

The study was described as a pilot intended to assess feasibility and explore preliminary effects. That aim is different from providing a definitive estimate of treatment effect. In general, pilot studies can help describe recruitment and inform later research, but the registry record does not report a prespecified feasibility threshold or a sample-size justification for a later trial. The enrollment count alone cannot show whether recruitment met a target or whether the program was feasible according to a formal criterion.

The absence of a reported comparison does not show that the groups were equivalent, and it does not demonstrate benefit or lack of benefit. It means the record does not provide an inferential estimate for the comparison. Likewise, the absence of reported secondary outcome results is not evidence that outcomes did not change; it leaves their direction and magnitude unknown.

The study status is TERMINATED. The reason is not reported in the registry record, so the status cannot be used to infer the cause of termination or its relationship to the results. The record does not report participant-level characteristics, follow-up completeness, adherence, or analysis populations. Those omissions make it difficult to assess how representative the posted enrollment counts are of the intended study population and whether outcome data could support further conclusions.

Overall, the posted data describe enrollment and safety counts, while leaving intervention effects and their precision unresolved. They should not be interpreted as a clinical recommendation or as evidence that the sleep program does or does not work.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a feasibility-oriented primary outcome and a clinical outcome. The registered primary endpoint counts enrollment, while the study description frames sleep and cognition as areas for exploring preliminary effects. A recruitment count can describe enrollment, but it cannot substitute for comparative results on actigraphy-assessed sleep or neurocognitive function.

It also shows why endpoint definitions and analysis labels matter. The primary outcome title and unit describe a participant count, while the unavailable-comparison note refers to a binary endpoint. The registry record does not explain that difference. Since statistical methods depend on the outcome’s scale and definition, this ambiguity limits interpretation of how the comparison was intended to be analyzed.

Reporting an arm-level count without an estimable comparison leaves important statistical questions unanswered. No treatment-effect estimate, uncertainty interval, or test result is reported. Readers therefore cannot judge the magnitude or precision of a group difference from the record. The counts remain useful as descriptive information, but they do not support a claim about an effect on sleep or cognition.

The record’s terminated status, alongside the absence of a reported reason, is another reminder that registration details and outcome reporting answer different questions. Status does not explain the available data, and enrollment counts do not clarify why the study ended. For researchers, clear reporting of endpoint definitions, analysis populations, missing-data handling, and reasons for study changes can make even a pilot record more interpretable. Those details are not reported in the registry record.

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 available information has important trial-specific limitations. The registry record gives enrollment counts by arm but no estimable two-arm comparison for the primary endpoint. It provides no effect estimate, confidence interval, or p-value for that comparison. It also lists zero analyses, so no analysis results are available for assessing uncertainty or comparing groups.

The primary outcome is described as a count of enrolled participants, while the note about the unavailable comparison labels the endpoint binary. The record does not explain this difference. The analysis method and intended estimand therefore cannot be reconstructed from the posted information. The record does not report participant characteristics, eligibility details beyond the broad target population, or the number contributing data to secondary outcomes.

Although sleep and cognitive function are listed as secondary outcomes, their results are not reported. The record does not describe adherence, treatment completion, follow-up completeness, missing-data procedures, analysis populations, or outcome measurement schedules. It also does not report the randomization method, masking roles, a detailed statistical plan, or the reason the study was terminated.

The study is described as a pilot, and its enrollment field lists 15. The posted arm counts are 8 and 7. These figures alone do not provide a basis for judging the precision of a treatment-effect estimate, particularly because no such estimate is reported. Safety counts are also reported without event definitions, collection period, or comparative analysis. These limitations constrain interpretation to descriptive enrollment and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Napping, Sleep, Cognitive Decline and Risk of Alzheimer's Disease — NCT03256539.
• Registry record last updated 2025-11-14; status last verified 2025-10.
• Results first posted 2025-11-14.
• 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

NCT03256539 is a randomized, double-masked, parallel-group pilot study sponsored by the University of California, San Francisco. It compared a behavioral sleep program incorporating modified cognitive behavioral therapy for insomnia and bright light therapy with a behavioral placebo intervention described as quasi-desensitization. The intended population was people with mild cognitive impairment or mild Alzheimer’s disease.

The primary endpoint was the number of participants enrolled, measured over up to 24 weeks following study initiation. The posted arm counts are 8 for the Sleep Intervention and 7 for the Placebo Intervention. The registry record reports no estimable two-arm comparison for the primary endpoint. It lists actigraphy-assessed sleep and neurocognitive function as secondary outcomes but does not report their results. The record status is TERMINATED; the reason is not reported in the registry record.