Treatment of Insomnia and Glucose Metabolism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Insomnia and Glucose Metabolism (NCT00724282), a randomized phase 4 study. The primary outcome is Plasma Glucose Level at the 120-minute Time Point of a 75g Oral Glucose Tolerance Test.

2. Clinical Question

The central question is whether glucose handling, assessed by plasma glucose after a glucose challenge, differs between the eszopiclone and placebo treatment periods in adults with chronic insomnia. The registry describes the rationale as a hypothesis: improving sleep with eszopiclone might also improve the body's use of sugar. That rationale is not itself evidence of an effect, and the registry record does not report an analyzed comparison of the glucose measurements.

Because the design is a crossover, the question concerns measurements under both treatments within a study organized around treatment periods, rather than a reported comparison of two independent groups. The record says participants received either eszopiclone or placebo, then crossed over to the opposite treatment after washout. It does not report the order assigned to individual participants, whether all planned measurements were obtained, or how period and sequence were handled in an analysis.

The primary endpoint names a specific time point in an oral glucose tolerance test. It therefore addresses plasma glucose at that point, not every aspect of glucose metabolism, insulin secretion, insulin action, sleep quality, or future diabetes risk. Those broader topics appear in the study rationale or official title, but no analyzed results for them are reported in the registry record.

3. Trial Design

This was a randomized, quadruple-masked, phase 4 crossover study sponsored by the University of Chicago. The registry lists an enrollment of 20 and a completed status. The study's official title describes a double-blind, placebo-controlled study of eszopiclone's effects on glucose tolerance, insulin secretion, and insulin action in adults with chronic insomnia.

The arm description says participants received either eszopiclone or placebo for 9 days, followed by a 3 week washout, and then crossed over to the opposite treatment. The description also calls the treatment double-blinded, while the registry's masking classification is quadruple. The registry does not identify which roles were masked, explain the difference in wording, or describe how masking was maintained or assessed.

A crossover design exposes participants to both treatments in sequence, as described in the record. This allows a treatment comparison to use information from the same participants under each treatment, but interpretation depends on details such as treatment order, period effects, carryover, and completeness of observations. The registry record does not report the treatment sequences, how these design features were incorporated into an analysis, or whether the washout was evaluated for adequacy.

The study began in 2008-04, with primary completion in 2012-03. The registry lists one outcome measure and no analyses. For the primary endpoint, the record specifies plasma glucose at the 120-minute time point of a 75g oral glucose tolerance test, measured at the end of each treatment. It gives no unit, estimate, measure of variability, confidence interval, or statistical test. The record states that the investigator left the university without analyzing data and that no information is available on unblinding. Thus, the design and intended measurement are described, but the planned comparison's result cannot be evaluated from 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.

Before assignment: Investigator left academia and is unavailable; participation in cross-over sequences was not unblinded, therefore participants are presented in one Arm throughout Results.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Investigator left university without analyzing data and no information is available on unblinding.

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 Plasma Glucose Level at the 120-minute Time Point of a 75g Oral Glucose Tolerance Test, measured over at the end of each treatment.

The primary endpoint is plasma glucose at the 120-minute time point of a 75g oral glucose tolerance test, measured at the end of each treatment. In general, an oral glucose tolerance test assesses the body's handling of a standardized glucose challenge by measuring glucose after ingestion. A measurement at a specified time point gives a defined outcome for comparison between treatment periods; it does not by itself describe the full glucose response over time.

The registry's rationale links sleep and glucose metabolism and proposes examining whether eszopiclone-associated sleep improvement might also affect sugar use. Plasma glucose after a glucose challenge is relevant to that question because it directly measures circulating glucose at the stated time. It is distinct from the other concepts named in the official title: insulin secretion and insulin action. The primary endpoint cannot, on its own, establish changes in those processes or in sleep.

The record does not state a unit for the endpoint and does not report the measured values, an effect estimate, or variability. It also does not report how many participants contributed measurements at each treatment endpoint. As a result, the endpoint can be described in terms of what it was intended to measure, but its observed level and the precision of any treatment comparison are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies random allocation, quadruple masking, and a crossover model. These describe important aspects of trial conduct, but they do not supply the statistical analysis used for the primary endpoint. The registry lists no analyses, and the primary outcome entry reports no estimate or test. The investigator's departure without analyzing data is noted; an analysis plan, model specification, and account of unblinding are not reported in the registry record.

What does randomization contribute?

In general, random allocation helps prevent deliberate or systematic assignment of participants to a preferred treatment sequence. It can support a fair comparison by reducing the influence of factors that might otherwise differ between assigned groups. In a crossover trial, randomization may concern treatment order or sequence, but the registry does not report the sequences or how allocation was implemented. Randomization alone does not guarantee that all measurements are complete or that an analysis is unbiased; those questions require information about conduct and analysis.

What does masking mean?

Masking is intended to limit the influence of treatment knowledge on participant experience, treatment delivery, outcome assessment, or interpretation. The registry classifies masking as quadruple and describes the treatment as double-blinded. It does not specify which people were masked or reconcile these descriptions. No information about unblinding is available in the record. Without those details, the masking classification can be reported, but its implementation and success cannot be evaluated.

Why does crossover structure matter?

In general, a crossover design measures participants during more than one treatment period. Since the same participant contributes information under both treatments, an analysis can account for within-participant pairing. Such pairing is not equivalent to treating all treatment-period measurements as independent. A suitable analysis also needs to consider period and sequence effects and whether a prior treatment could influence measurements in a later period. The registry says there was a 3 week washout between treatments, but does not report the statistical approach to these design features or evidence about carryover.

The arm description states that participants received either eszopiclone or placebo for 9 days and then crossed over to the opposite treatment. It does not state how many participants completed each period, whether any participants stopped treatment, or whether glucose measurements were obtained at both endpoints. The listed enrollment of 20 cannot be assumed to equal the number included in an endpoint analysis.

What can an effect estimate and confidence interval tell readers?

In general, an effect estimate quantifies the comparison being studied, while a confidence interval describes uncertainty around that estimate under the analysis assumptions. For a crossover endpoint, interpretation would depend on how the treatment-period measurements were compared and what population was analyzed. A test result alone would not convey the magnitude or precision of a difference. The registry record reports no primary outcome estimate, confidence interval, or test result, so none of these features can be assessed for this study.

Why can variability and distribution matter?

In general, statistical methods rely on assumptions about the outcome's distribution and variability. When measurements vary more than a model assumes, uncertainty estimates and tests may be unreliable unless the analysis allows for that variation. Repeated measurements from the same participant can also be correlated; an analysis should account for that dependence rather than treating each measurement as unrelated. The record gives no outcome values, measure of dispersion, distributional assessment, or statistical model. It is therefore not possible to determine which assumptions would be relevant to the observed data or whether they were checked.

How should planning illustrations be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, allocation, and a chosen statistical procedure. It is not an observed trial result and does not show that a study had a particular probability of finding an effect after the fact. The planning description associated with this study refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect; it also distinguishes participants per arm from total events for time-to-event outcomes. Those assumptions describe a planning illustration, not a reported design justification or an analysis of this crossover study. The registry record does not report the trial's own sample-size justification or an observed primary effect estimate. The illustration should not be interpreted as observed power or as evidence that the primary comparison was analyzed.

Statistical methods can clarify how an endpoint was compared and how uncertain the estimate is, but they cannot replace the missing outcome data. Here, the record identifies the intended outcome and design while leaving the analysis and primary result unreported. Any methodological interpretation beyond those details would require information not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. The primary endpoint is plasma glucose at the 120-minute point of a 75g oral glucose tolerance test at the end of each treatment. The official title also names glucose tolerance, insulin secretion, and insulin action, but the registry does not provide analyzed results for these broader topics. It does not report whether additional outcomes were prespecified, analyzed, or considered in deciding what to report. A multiplicity strategy, such as adjustment across multiple statistical tests, is not reported in the registry record.

Missing-data handling is also not described. The record does not state whether endpoint measurements were missing, how many participants completed each treatment period, why measurements might be unavailable, or whether any imputation or other method was planned or used. The listed enrollment of 20 does not establish how many participants contributed to a primary endpoint analysis.

The analysis population is not reported. There is no account of whether the intended analysis included all randomized participants, only participants completing both periods, or another set of participants. No protocol deviations, exclusions, or treatment discontinuations relevant to the endpoint are described in the results entry.

These omissions matter because decisions about outcomes, missing measurements, and the analysis population can affect interpretation. The record states that the investigator left the university without analyzing data and that no information is available on unblinding. Accordingly, there is no reported multiplicity procedure, missing-data method, or analysis population against which the primary result can be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 reports adverse-event counts for a combined group titled “Eszopiclone or Placebo.” For serious adverse events, 20 participants were at risk and 0 were reported as affected. For other adverse events, 20 were at risk and 1 was reported as affected. Deaths are listed as null, which means a death count is not reported; it should not be read as a reported count of zero.

The record does not identify the non-serious adverse event's term, provide a breakdown by treatment period, or show separate counts for eszopiclone and placebo. The combined group label limits treatment-specific interpretation. The adverse-event figures therefore describe what the registry recorded for the group, not a comparative estimate of risk between treatments.

In general, adverse-event counts depend on how events were defined, collected, and reported, and a count alone does not establish whether an event was caused by a treatment. The record does not provide those details or an analysis comparing treatments. The counts should be read as descriptive registry entries, not as evidence that an event was or was not related to either treatment.

The enrollment and at-risk figures do not establish that every participant completed both crossover periods or was observed for the same duration under each treatment. The record does not report period-specific safety follow-up. These limitations make it impossible to use the posted counts to evaluate a treatment-specific safety difference.

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

The record shows that a randomized, quadruple-masked crossover study was completed and that it intended to compare eszopiclone with placebo in adults with chronic insomnia. Its primary endpoint was plasma glucose at the 120-minute point of a 75g oral glucose tolerance test at the end of each treatment. The intervention description specifies 9 days of treatment followed by a 3 week washout and crossover to the opposite treatment.

Those design details describe the question the study set out to address; they do not answer it. The registry does not report primary endpoint measurements, a treatment comparison, an uncertainty interval, or an analysis. It is therefore not possible to determine from the posted results whether glucose values differed between treatment periods, in which direction they might have differed, or how precisely any difference could be estimated.

The absence of a reported analysis is not evidence that eszopiclone had no effect, and it is not evidence that it did have an effect. It means that the registry record does not provide the analyzed outcome needed to make either claim. The record notes that the investigator left the university without analyzing the data and that information about unblinding is unavailable.

The primary endpoint is also narrower than the full set of biological topics in the official title. A glucose measurement at one specified time point does not by itself establish an effect on insulin secretion, insulin action, sleep, or long-term diabetes risk. The study rationale discusses possible links between sleep and glucose metabolism, but a rationale is not a finding.

The safety entries are similarly limited: they provide a serious-event count of 0 among 20 at risk and an other-adverse-event count of 1 among 20 at risk for the combined “Eszopiclone or Placebo” group. They do not distinguish the treatments, and deaths are not reported. Taken together, the registry record supports a description of the design, endpoint, and limited adverse-event entries, but not a conclusion about comparative efficacy or treatment-specific safety.

13. Why This Trial Matters Statistically

This study is statistically notable because its crossover structure makes within-participant comparisons central to the intended question. In general, such designs can use measurements from the same participants under both treatments, but the analysis must respect the repeated nature of the observations. Treatment order, period effects, possible carryover, and missing measurements can all be relevant. The registry describes the crossover and washout but does not report how these matters were analyzed.

The record also illustrates the distinction between a completed trial and a reported analysis. The study is listed as completed, with an enrollment of 20, yet the registry reports zero analyses and no primary outcome estimate. Completion status alone does not establish that the planned statistical comparison was performed or that its results are available.

For clinical research, a specified endpoint is valuable because it identifies the intended measurement and timing. Here, the primary outcome is precisely named as plasma glucose at 120 minutes after a 75g oral glucose tolerance test. But without values and an analysis, endpoint specificity cannot establish an effect or its precision. The absence of an analysis prevents readers from assessing the magnitude of the comparison, its uncertainty, and the assumptions used to obtain it.

Reporting the analysis population and missing-data approach would also be important in a crossover study, where participants may have measurements from one treatment period but not the other. Those details are not reported in the registry record. Without them, even the relationship between the listed enrollment and the information contributing to the endpoint remains unclear.

The statistical importance of the record is therefore not a treatment conclusion. It is a reminder that trial design, outcome definition, analysis, and transparent reporting are distinct parts of evidence. The record documents the first parts of the planned comparison but does not report the analysis needed to interpret the primary clinical measurement.

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 is that the registry record contains no analyzed primary outcome result. It identifies the plasma glucose endpoint and its timing but gives no observed values, treatment estimate, measure of variability, confidence interval, or test. The record says the investigator left the university without analyzing data. As a result, the intended comparison cannot be evaluated statistically from the posted results.

Details needed to assess the crossover analysis are also absent. The record does not report treatment sequences, period-specific measurements, handling of period or sequence effects, assessment of carryover, or the number of participants completing both periods. Although a 3 week washout is described, the record does not explain its rationale or report whether residual effects were assessed.

The endpoint unit is not stated. The number of participants with usable measurements is not reported, and the analysis population, missing-data handling, exclusions, and protocol deviations are not described. These gaps prevent assessment of the data available for the primary comparison and the assumptions that an analysis would require.

Masking is described with both a quadruple classification and a double-blind treatment description, without identifying masked roles. The registry also states that information on unblinding is unavailable. It does not report a statistical analysis plan, multiplicity approach, or the trial's own sample-size justification. The planning assumptions listed for illustrations do not substitute for those trial-specific details or for an observed effect estimate.

Safety reporting is limited to a combined treatment-group entry, with no event term for the other adverse event, no treatment-specific breakdown, and deaths listed as null. These limitations are specific to the registry information and do not establish what unreported data may contain.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Insomnia and Glucose Metabolism — NCT00724282.
• Registry record last updated 2015-10-16; status last verified 2015-10.
• Results first posted 2015-10-16.
• 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.

18. Record Summary

NCT00724282 is a completed, randomized, quadruple-masked, phase 4 crossover study sponsored by the University of Chicago. It lists an enrollment of 20 and concerns adults with chronic insomnia. The described sequence involved eszopiclone or placebo for 9 days, a 3 week washout, and crossover to the opposite treatment.

The primary endpoint was plasma glucose at the 120-minute point of a 75g oral glucose tolerance test at the end of each treatment. The record lists one outcome measure and zero analyses. It states that the investigator left the university without analyzing data and that no information is available on unblinding.

For the combined “Eszopiclone or Placebo” group, the registry reports 0 serious adverse events among 20 at risk and 1 other adverse event among 20 at risk. Deaths are not reported. No primary outcome estimate or treatment-specific safety comparison is available in the registry record.