Metabolomics of Insomnia-Related Hyperarousal: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Metabolomics of Insomnia-Related Hyperarousal (NCT01957111), a registered phase not stated study. The primary outcome is Number of Metabolites Elevated Relative to the Other Group..

2. Clinical Question

The study addresses a biological question rather than a treatment-effect question. Its summary begins from the observation that people with insomnia have been shown to have higher overall metabolic rates than good sleepers, while the processes associated with that difference are not known. The stated hypothesis is that distinct metabolic processes function differently in people with insomnia.

The registry describes a comparison of metabolite profiles, with blood samples analyzed using spectroscopy. This approach is described as producing rapid, unbiased and quantitative metabolic profiles, or “fingerprints.” The primary outcome counts metabolites elevated relative to the other group; it does not, by itself, describe the size of any elevation or identify the biological importance of a particular metabolite.

Sleep efficiency percentage on an overnight sleep study is listed as a secondary outcome. The registry record does not report a result for that measure or for the primary metabolite outcome. The clinical question can therefore be described from the stated aims and endpoint, but the posted information does not establish whether the observed profiles differed or how precisely any difference was estimated.

3. Trial Design

The registry describes a completed study titled “Metabolomics of Insomnia-Related Hyperarousal,” sponsored by the University of Pennsylvania. Its listed condition is primary insomnia. The study started in 2013-10, reached primary completion in 2015-10, and has completed status.

The brief summary describes an intended comparison involving 15 people with insomnia and 15 good sleepers. Registry enrollment is 32. The arm names are “Individuals with insomnia” and “Good sleepers,” but the arm descriptions are blank. The enrollment figure should not be treated as a reported group-by-group count: the registry record does not provide actual analyzed group sizes or explain how the enrolled participants were distributed between the arms.

This is not reported as a randomized comparison. Allocation is not stated, and the registry record characterizes the arms as not being a like-for-like control comparison. No assigned intervention is described. The available information therefore supports describing a comparison between groups, but not a randomized treatment contrast or a causal estimate of an intervention effect.

The primary outcome is the number of metabolites elevated relative to the other group, with a timeframe of 48 hours. The outcome description says that blood samples were analyzed with spectroscopy and that 70 metabolites were measured and compared. Sleep efficiency percentage on an overnight sleep study is listed as a secondary outcome. The record lists 2 outcome measures, but does not describe how either was analyzed.

Study details such as eligibility criteria, recruitment methods, participant characteristics, procedures for assigning or defining groups, and the handling of potential confounders are not reported in the registry record. The record also does not provide the protocol or statistical analysis plan. These omissions limit what can be inferred about how comparable the groups were and how closely the completed study followed its stated aims.

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 Metabolites Elevated Relative to the Other Group., measured over 48 hours.

The primary endpoint is the number of metabolites elevated relative to the other group. The endpoint description states that 70 metabolites were measured in blood samples using spectroscopy, which is presented as a way to obtain rapid, unbiased and quantitative metabolic profiles. The stated timeframe is 48 hours.

A count of elevated metabolites offers a compact way to describe how many measured metabolites point in the stated direction of comparison. It can summarize a broad profile without reducing the study question to a single named metabolite. The study summary’s motivation is that overall metabolic rates have been reported as higher among people with insomnia, while the processes involved are not known. Comparing a set of measured metabolites is intended to explore that broader biological question.

The count has important interpretive limits. It does not reveal the magnitude of each metabolite’s elevation, the variability of those measurements, or whether a small number of metabolites account for most of the pattern. A count also depends on how “elevated” was defined and how comparisons across the measured metabolites were handled. Those operational details are not reported in the registry record.

The registry record does not report the primary endpoint’s observed value, a group-specific result, or an uncertainty estimate. It therefore describes what the endpoint was intended to measure, but does not show whether the measured profiles differed or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how measurements are turned into estimates and how much confidence readers can place in those estimates. For this study, the registry describes a count endpoint based on metabolite measurements, but does not report the analysis method, numerical results, or uncertainty estimates. The explanations below describe general considerations for this kind of question; they are not claims about methods used in the study.

What does the endpoint count?

The stated endpoint counts metabolites elevated relative to the other group. The description reports measurement of 70 metabolites and identifies spectroscopy as the measurement approach. For a count to be reproducible, an analysis needs a clear rule for deciding when a metabolite is elevated, including the comparison being made and any threshold used. The registry record does not report that rule.

There is also a distinction between the count and the underlying measurements. The count summarizes how many metabolites meet the elevation criterion, whereas individual metabolite measurements retain information about the size and spread of each difference. A count can be useful as a broad summary, but it can conceal whether the qualifying metabolites have small or large differences and whether some measurements are more variable than others. The record does not include metabolite-level estimates that would allow those features to be assessed.

How might a group comparison be analyzed?

In general, an analysis would need to account for the form of the outcome and the structure of the data. Counts are nonnegative and may have a distribution different from measurements that vary continuously. A simple model may not describe the data well if the variability is greater than the model expects; this is often called over-dispersion. Over-dispersion matters because a model that understates variability can produce uncertainty estimates that are too narrow. This is a general statistical consideration, not a reported feature of this study’s data.

The endpoint’s wording also raises a question about the unit of analysis. It describes a number of metabolites elevated relative to another group, but does not state whether the count was calculated at the participant level, from group-level comparisons, or by another procedure. The registry record does not identify the analysis unit, the statistical model, or how measurements from participants were combined. These details are necessary to interpret what a reported count would represent.

Because this is not reported as a randomized comparison and allocation is not stated, group composition is relevant. In general, researchers may describe or adjust for factors that differ between groups and are related to the outcome. The registry record does not report participant characteristics, potential confounders, or adjustment methods. It is therefore not possible to determine whether the posted comparison, if any, was adjusted or how comparable the groups were.

What would uncertainty estimates add?

A confidence interval is a general way to express uncertainty around an estimate. It describes a range of values compatible with the data under the assumptions of the analysis; it does not guarantee that the true value lies within that particular interval. A statistical test addresses a related but different question, assessing how compatible the data are with a specified null model. Neither an interval nor a test replaces consideration of the estimate’s size, the measurement process, and the study design.

The registry record does not report a confidence interval, standard error, test statistic, or p-value for the primary endpoint. It also lists no analyses. There is thus no posted statistical evidence from which to judge precision, distinguish a small estimate from a large one, or assess compatibility with a null comparison. No result should be inferred from the absence of these details.

How should the planning illustrations be understood?

The sample-size assumptions describe planning illustrations based on an observed effect, rather than the trial’s original design. They specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. These assumptions do not document that the study was planned using those criteria, and the illustrations are not observed power.

For a count outcome, the suitability of a normal approximation depends on the data and the analysis. That cannot be evaluated from the registry information because the observed effect and its variability are not reported. The planning illustrations should therefore be understood as conditional calculations, not as evidence about the study’s actual precision or ability to detect a biological difference.

What remains unknown about the analysis?

The registry record does not report the prespecified analysis, the handling of missing measurements, any transformation or normalization of metabolite measurements, or whether multiple comparisons were addressed. It does not state whether analyses were adjusted, whether subgroup analyses were planned, or whether any interim analyses occurred. None of these procedures should be assumed. The reported endpoint and measurement description establish the broad analytic subject, but not the methods needed to reproduce or critically assess a result.

10. Multiplicity, Missing Data and Analysis Populations

The study measured 70 metabolites, while the registered primary endpoint is a count of metabolites elevated relative to the other group. Testing many metabolites separately can create a multiplicity concern: as the number of tests grows, the chance of finding at least one apparently unusual result by chance can increase. General approaches to this issue include prespecifying a primary comparison or adjusting interpretation for multiple tests. The registry record does not state whether individual metabolite tests were conducted, what criteria defined elevation, or whether any multiplicity procedure was planned or used.

The record lists 2 outcome measures: the primary count of elevated metabolites and sleep efficiency percentage on an overnight sleep study. It does not explain how the primary and secondary outcomes were prioritized analytically, whether additional outcomes were measured, or how results across outcomes were interpreted. The registry lists no analyses, so it is not possible to assess whether the analysis followed a prespecified plan.

Missing-data handling is not reported in the registry record. The enrollment figure is 32, while the study summary describes intended groups of 15 people with insomnia and 15 good sleepers. The record does not report analyzed group sizes, completeness of blood measurements or sleep-study measurements, exclusions, or reasons for any missing data. It is not possible to determine whether the primary endpoint was calculated for all enrolled participants or whether missingness could have affected the comparison.

The analysis populations are also not described. The registry record does not say which participants were included in the primary or secondary outcome analyses, or how group membership was established for analysis. Without that information, a reader cannot relate enrollment to the population contributing data to the endpoint. These are reporting gaps, not proof that missing data or analysis problems occurred.

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.

The adverse-event figures list 16 participants at risk in each group. The registry reports 0 serious adverse events for individuals with insomnia and 0 for good sleepers. It also reports 0 other adverse events in each group. Death figures are not reported in the registry record.

These counts describe what the registry lists; they do not show that the study was designed or powered to evaluate safety. The record does not provide details about how adverse events were defined, collected, or attributed, or about the period over which they were monitored. It also does not explain whether the figures cover every enrolled participant or only participants in the listed safety groups.

Zero recorded events should not be interpreted as proof that no event could occur or that an intervention is safe. No assigned treatment is described, and this study is framed as a comparison of insomnia and good-sleeper groups. The safety figures are best read as registry-reported event counts with limited accompanying context. The unreported death figures should not be read as zero deaths.

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

The registry record makes the study’s purpose clear: compare metabolite profiles in people with insomnia and good sleepers to explore processes that may differ between the groups. It identifies a broad measurement approach, a count-based primary endpoint, and sleep efficiency as a secondary outcome. These details explain the scientific question the study was designed to address.

The record does not report the primary outcome result, the secondary outcome result, or any statistical analyses. It therefore cannot show whether metabolites were elevated, how many met the endpoint criterion, whether the groups differed in sleep efficiency, or how precise any estimate was. An unreported result is not equivalent to a finding of no difference.

Even a reported difference would need cautious interpretation. The study is not described as randomized, allocation is not stated, and the arms are not characterized as a like-for-like control comparison. Without information about participant characteristics, group formation, or adjustment, a difference could not automatically be attributed to insomnia. The study’s stated hypothesis about distinct metabolic processes would require detailed findings beyond the broad count endpoint to identify which processes might be involved.

The count of elevated metabolites also has limits as a summary. It does not convey the magnitude of each measurement difference or its uncertainty. A complete interpretation would need the endpoint definition, analyzed group sizes, metabolite-level results or other supporting analyses, and a description of how multiplicity and missing data were handled. Those details are not reported in the registry record.

The study therefore contributes a defined research question and a described measurement strategy, but the posted information does not support a conclusion about the direction, size, or reliability of any biological difference. It also does not support a treatment recommendation or a claim that a treatment works or does not work.

13. Why This Trial Matters Statistically

This study is statistically interesting because it turns a broad biological question into a comparison across a large set of measured metabolites. The registry describes 70 measured metabolites and makes the primary endpoint a count of those elevated relative to the other group. That choice offers a compact profile-level summary, while also making the definition of “elevated” and the treatment of multiple measurements important for interpretation.

The study also illustrates the distinction between study aims and reported evidence. The summary states a hypothesis about metabolic processes in insomnia, and the registry identifies the outcome intended to address it. But without posted outcome values, analyses, or uncertainty estimates, readers cannot assess whether the data support that hypothesis. Clear registration of the question is valuable, but it does not substitute for reporting results and methods.

Group comparability matters in this setting. The comparison is not described as randomized, allocation is not stated, and the registry characterizes the arms as not being a like-for-like control comparison. For group-based biological measurements, differences in participant composition or other factors can complicate interpretation. The registry record does not provide the detail needed to judge that concern.

The planning illustrations also highlight a useful distinction: calculations based on an observed effect are not the same as evidence about the design or performance of the completed study. Their assumptions are stated, but the observed effect and analysis results are not reported in the registry information. They cannot establish observed power or supply missing evidence about precision.

Statistically, the record is most useful as a description of the intended question and measurement framework. It also shows why complete reporting matters: endpoint definitions, analysis methods, missing-data handling, group characteristics, and numerical results are needed to connect a biological hypothesis to a defensible estimate.

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 registry information leaves several trial-specific questions unanswered. Although the brief summary describes intended groups of 15 people with insomnia and 15 good sleepers, actual analyzed group sizes are not reported. Enrollment is 32, but the record does not describe participant flow, exclusions, or how many participants contributed blood or sleep-study data. The blank arm descriptions provide no further detail about group composition or procedures.

The outcome definition is also incomplete for interpretation. The primary endpoint is the number of metabolites elevated relative to the other group, but the record does not state the criterion for elevation, the analysis unit, or how measurements were combined to form the count. While spectroscopy and measurement of 70 metabolites are described, measurement processing and the handling of missing or unusable measurements are not reported.

No primary or secondary outcome values are included in the registry information, and the record lists no analyses. There are no reported uncertainty estimates, statistical tests, or metabolite-level findings. The registry does not state whether comparisons were adjusted for participant characteristics or whether multiplicity was addressed. The relevance of the sleep efficiency outcome to the metabolite comparison is not explained.

Design details that would help assess group comparability are not reported, including eligibility criteria, recruitment methods, and participant characteristics. The record does not describe random allocation; it characterizes the study as not a randomized comparison, with allocation not stated and arms not like-for-like controls. This limits causal interpretation and leaves potential sources of group difference unresolved.

These are limitations of the information available in the registry record. They do not establish that the study lacked procedures or that its analyses were inadequate; they mean that those procedures and results cannot be evaluated from the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Metabolomics of Insomnia-Related Hyperarousal — NCT01957111.
• Registry record last updated 2017-01-11; status last verified 2016-11.
• Results first posted 2017-01-11.
• 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

“Metabolomics of Insomnia-Related Hyperarousal” is a completed University of Pennsylvania study of primary insomnia. The registry lists a start of 2013-10, primary completion in 2015-10, and enrollment of 32. The study summary describes an intended comparison of 15 people with insomnia and 15 good sleepers.

The primary endpoint is the number of metabolites elevated relative to the other group, based on spectroscopy of blood samples. The outcome description says 70 metabolites were measured, with a 48 hours timeframe. Sleep efficiency percentage on an overnight sleep study is listed as a secondary outcome.

The registry record does not report outcome results, analysis methods, analyzed group sizes, or uncertainty estimates; it lists no analyses. It does not describe a randomized comparison, and the arms are not characterized as like-for-like controls. The record therefore documents the study question and broad measurement approach, but does not permit assessment of the magnitude, direction, or precision of any metabolite or sleep-efficiency difference.