This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Sleepiness and the Effects of CPAP on Salivary Cortisol and Alpha-Amylase Levels in Patients With Sleep Apnea (NCT01196117), a non-randomized na study. The primary outcome is Salivary Cortisol Level.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01196117 |
| Phase | NA |
| Condition | Sleep Apnea, Sleep Disordered Breathing |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Medical College of Wisconsin |
| Results posted | Yes |
2. Clinical Question
Population
Patients with sleep apnea, including obstructive sleep apnea syndrome in the study summary. The registry lists an enrollment of 18.
Intervention
Continuous positive airway pressure (CPAP) therapy for 14 days. The record also describes a group receiving 14 days of placebo therapy followed by CPAP.
Comparator
Placebo therapy, described as guaifenesin in the arm description. The registry identifies the allocation as non-randomized, so the arms should not be treated as a like-for-like randomized comparison.
Primary question
How does salivary cortisol change from baseline on Day 0 to the average of Day 1, Day 7 and Day 14? The record does not report the primary outcome data or the estimated change.
The study also addresses sleepiness and salivary alpha-amylase in its brief summary. That summary proposes examining whether these measures change with CPAP and relate to subjective sleepiness, the Psychomotor Vigilance Test and pupillometry. The listed primary endpoint, however, is salivary cortisol. The registry record does not report a primary cortisol result, a comparison estimate, or the precision of an estimate.
The clinical question is therefore more specific than whether CPAP changes sleepiness overall: it concerns a biomarker measured in saliva across treatment periods, with measurements collected at approximately 7am and 11pm. The brief summary also describes a relationship between biomarker levels and sleepiness measures. The record does not report results for that relationship, and it does not establish whether all the measures named in the summary were analyzed.
Because the study is non-randomized, any observed contrast between treatment conditions could reflect differences other than treatment. The crossover label indicates that the design involves treatment periods within a crossover framework, but the record does not report enough detail about sequence assignment, timing between periods, or analysis to establish how those concerns were addressed.
3. Trial Design
The registry identifies this as a completed, non-randomized crossover study sponsored by the Medical College of Wisconsin. Enrollment is listed as 18. The record gives a start date of 2004-11-15 and a primary completion date of 2011-12-15. It lists no masking and gives the study phase as not applicable.
The interventions are 14 days of placebo therapy and 14 days of CPAP therapy. One arm is described as receiving 14 days of placebo therapy followed by CPAP. Its description specifies guaifenesin during the placebo period, with salivary cortisol measurement and Epworth Sleepiness Score documentation. The other arm is described as receiving 14 days of CPAP therapy, also with cortisol measurement and Epworth Sleepiness Score documentation.
The record labels the overall model as crossover, but it does not report a complete account of the treatment sequence, how participants were assigned to sequences, or whether there was a washout period. It also does not report whether treatment order was balanced or how period effects were handled. Since allocation is explicitly non-randomized, treatment comparisons may be affected by participant differences or other factors related to assignment. The record itself cautions that the arms are not a like-for-like control comparison.
The primary endpoint is described as the difference between baseline on Day 0 and the average of Day 1, Day 7 and Day 14. Saliva samples were described as collected at approximately 7am and 11pm on each of those days. The registry lists additional cortisol outcomes at those times across the study days. It does not report the primary outcome results, a complete analysis population description, or the statistical analysis plan.
The brief summary describes sleepiness and alpha-amylase as part of the study's aims. The arm descriptions specifically mention cortisol and the Epworth Sleepiness Score. The registry does not report a complete account of how the other measures named in the summary were collected or analyzed.
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: Participants without prior treatment of obstructive sleep apnea (OSA) or overt airway structural pathology that would interfere with continuous positive airway pressure (CPAP) were recruited.
Placebo, Then CPAP
| Stage | 14 Days of Placebo Therapy | 14 Days of Continuous Positive Airway Pressure (CPAP) Therapy |
|---|---|---|
| STARTED | 18 | 0 |
| COMPLETED | 18 | 0 |
| NOT COMPLETED | 0 | 0 |
CPAP
| Stage | 14 Days of Placebo Therapy | 14 Days of Continuous Positive Airway Pressure (CPAP) Therapy |
|---|---|---|
| STARTED | 0 | 18 |
| COMPLETED | 0 | 18 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: We have made a best faith effort from a manuscript to determine the primary outcome measure; Salivary Cortisol Level; but access to the primary data has been lost and it additionally cannot be found in the manuscript. Despite all efforts to contact the PI/study team members, the statisticians and date are gone.
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.
| Characteristic | Unit | All Study Participants |
|---|---|---|
| Participants analysed | 18 | |
| Age, Continuous | years | 47 (SD 9) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 9 |
| Apnea-hyponea Index (AHI) | units on a scale | 30.8 (SD 32.1) |
| Body Mass Index | kg/m^2 | 33.8 (SD 6.2) |
6. Primary Endpoint
The registry lists the primary outcome as Salivary Cortisol Level, measured over Difference between Baseline(Day 0) and Average of Day 1,7,14..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is salivary cortisol level. The record says cortisol was measured using an enzyme-linked immunosorbent assay and identifies the endpoint as the difference between baseline on Day 0 and the average of Day 1, Day 7 and Day 14. Samples were collected by salivary swab at approximately 7am and 11pm on each stated day. The record also notes a reference range for healthy adults of <4.2 nmol/l; that reference is not a trial result or a threshold for treatment benefit.
Cortisol is a biological measure, while sleepiness is a symptom or performance-related outcome. Measuring cortisol can therefore address a biomarker question that is distinct from asking whether participants report less sleepiness or perform differently on an alertness measure. The study summary describes examining relationships among cortisol, alpha-amylase and sleepiness measures, but the registry record does not report those results.
For an endpoint defined as a change from baseline, interpretation depends on how the change is calculated and summarized, how observations from the morning and evening are handled, and how repeated measurements within a participant are modeled. The record does not report those analysis details. It also does not provide a cortisol estimate, a measure of variability, or a confidence interval. The registry states that primary data access had been lost and that the primary outcome could not be found in the manuscript, so the intended endpoint cannot be evaluated from a posted numerical result in this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended primary outcome and the time points used to define it, but it does not report the primary cortisol data or an estimated treatment effect. There is consequently no posted estimate from which to describe the direction or size of change, and no reported confidence interval or test result with which to assess its precision. The endpoint's numerical result is not reported in the registry record.
This absence matters because the study's stated question concerns change over time and a contrast involving CPAP and placebo. Descriptions of the planned measurements cannot substitute for observed outcome values. Nor does the stated reference range for healthy adults indicate what happened among participants in this study; it is context for interpreting cortisol, not evidence about the trial's result.
The non-randomized allocation is also important to interpretation. In a randomized comparison, allocation by chance is intended to reduce systematic differences between treatment groups. That protection cannot be assumed. The record itself warns that the arms are not a like-for-like control comparison. The crossover label does not, by itself, resolve this issue: the record does not explain how participants entered treatment sequences or how possible differences in period, sequence, or carryover were addressed.
The brief summary states an expectation that cortisol and alpha-amylase would be higher before treatment and decrease after consistent CPAP use compared with placebo, and that sleepiness would decrease and correlate with biomarker levels. These are statements of the study's anticipated findings, not results. The registry record does not report whether those expectations were supported by the observed data. There is also no reported estimate for the association between biomarkers and subjective sleepiness, the Psychomotor Vigilance Test, or pupillometry.
The record lists 10 outcome measures and 9 analyses, but does not provide a complete statistical plan or a mapping that explains which analysis corresponds to each outcome. It does not report how missing observations, repeated measurements, or multiple comparisons were handled. These omissions limit the ability to judge how robust any result would be even if a numerical estimate were available.
Safety entries list zero serious adverse events, zero other adverse events and zero deaths in each of the two groups, with 18 at risk recorded for each group. These entries describe what the registry reports for the listed groups; they do not establish that no events occurred outside the registry's reporting categories or observation period. The record does not provide further detail on safety ascertainment or follow-up.
In statistical terms, the study's design and endpoint are identifiable, but its primary result is not available in the registry record. Without an estimate and its uncertainty, the posted record cannot quantify the observed cortisol change or establish how compatible the data are with a range of possible effects.
9. Statistical Methods Explained
Methods determine how observations are converted into estimates and how uncertainty is represented. For this study, the record names a primary endpoint and a crossover model, but does not report the analysis methods used for the primary result. The concepts below are general explanations, not claims that a particular method was used in this study.
What does a change-from-baseline endpoint represent?
A change-from-baseline analysis compares a participant's later measurement, or a summary of later measurements, with that participant's starting value. This can account for differences in starting levels when estimating change. Here, the stated endpoint is a difference between Day 0 and the average of Day 1, Day 7 and Day 14. The record does not specify whether the average was calculated separately for morning and evening measurements, across measurement times, or using another approach. It also does not specify whether the endpoint was summarized as a mean, median, or another statistic.
Repeated measurements from the same participant are generally related rather than independent. A suitable analysis may need to account for that within-participant correlation. Treating correlated measurements as if they came from unrelated people can misstate uncertainty. The registry record does not say how repeated measurements were handled.
Why does crossover structure matter?
In a crossover study, participants may receive different conditions during different periods. Comparing measurements within a participant can reduce the influence of stable characteristics, because those characteristics are shared across periods. That advantage depends on the design and analysis being appropriate. Period effects, changes over time, sequence effects and carryover from an earlier treatment can affect measurements. A washout period, where relevant, and an analysis that accounts for period and sequence can be important considerations.
The registry identifies a crossover model, but does not report the sequence-assignment method, washout details, or a period-specific analysis. It also labels allocation non-randomized and warns against treating the arms as a like-for-like control comparison. Thus, the crossover label alone is not enough to infer that treatment periods were exchangeable or that potential biases were controlled.
What does a confidence interval communicate?
In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the statistical method. A narrower interval indicates greater precision for that estimate; a wider interval indicates less precision. The interval does not guarantee that the true effect lies within its bounds, and it cannot address biases caused by the design or data collection. The registry record does not report a confidence interval for the primary cortisol outcome.
A test result, such as a p-value, addresses compatibility between observed data and a specified statistical model under a null hypothesis. It does not describe the magnitude or clinical importance of an effect. A p-value is also not a substitute for an effect estimate and its uncertainty. No primary p-value or effect estimate is reported in the registry record.
What does over-dispersion mean?
In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If an analysis assumes less variability than is present, its uncertainty estimates can be too small and its tests can appear more decisive than warranted. Methods that account for over-dispersion can improve uncertainty estimates when the outcome and model call for them. The registry does not report an outcome model or indicate whether over-dispersion was assessed, so this is a general consideration rather than a description of the study's analysis.
How should planning illustrations be read?
The record describes sample-size planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not proof that the study had a particular probability of detecting an effect. A sample-size calculation is not observed power, and it does not replace an estimate of the result with an uncertainty interval.
Because the primary data and numerical effect are not reported in the registry record, the planning assumptions cannot be used to establish what effect was observed or how precisely it was estimated. The record also does not report the trial's original design justification or establish that the planning illustration reflects the study's original design. Any planning figures should therefore be understood only as prospective illustrations, not as evidence about the outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 10 outcome measures and 9 analyses. The primary outcome is salivary cortisol, while the listed secondary outcomes include cortisol measurements at approximately 7am and 11pm on Day 0, Day 1, Day 7 and Day 14. The record does not explain how the analyses map to the outcomes, which comparisons were considered primary for inference, or whether any multiplicity adjustment was used.
In general, when investigators test or estimate many outcomes or contrasts, the chance of finding an apparently notable result by chance can increase. A prespecified hierarchy, adjustment procedure, or clear separation of primary and exploratory analyses can help readers interpret multiple results. The registry record does not report whether such an approach was used. This is particularly relevant because the brief summary mentions cortisol, alpha-amylase and several sleepiness-related measures, while the listed endpoint information focuses on cortisol.
The record notes that access to the primary data had been lost and that the primary endpoint could not be found in the manuscript. It does not report how many participants contributed data to each outcome, whether any measurements were missing, or how missing values were handled. It also does not define an analysis population or state whether all enrolled participants were included in each analysis.
For repeated measures, missingness at particular study days or times can affect the summary and the assumptions needed for analysis. General methods can use all available observations under specified assumptions, while other approaches may require complete measurements or imputation. The record does not identify which, if any, approach was used. As a result, the extent to which missing data or analysis-population choices could affect the intended endpoint is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 14 Days of Placebo Therapy, Then CPAP | 0 | 18 | 0.0% |
| 14 Days of CPAP Therapy | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 14 Days of Placebo Therapy, Then CPAP | 0 of 18 |
| 14 Days of CPAP Therapy | 0 of 18 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 14 Days of Placebo Therapy, Then CPAP | 0 of 18 |
| 14 Days of CPAP Therapy | 0 of 18 |
The registry lists two groups: “14 Days of Placebo Therapy, Then CPAP” and “14 Days of CPAP Therapy.” For each group, it records 18 at risk, zero serious adverse events, zero other adverse events and zero deaths. These are the safety entries reported for the groups.
A zero in a registry safety field means that no event is recorded for that category in the reported data. It should not be read as proof that the risk of an event is absent. The record does not provide further information about how adverse events were collected, the observation period used for safety reporting, or whether the same participant could contribute to multiple reporting periods. It also does not give event definitions beyond the registry categories.
The crossover design means that group labels may refer to treatment conditions or sequences rather than independent sets of participants. The registry's safety entries should therefore be read as posted, without adding the group counts or treating the groups as a randomized comparison. The non-randomized allocation and the record's warning that the arms are not a like-for-like control comparison apply to safety interpretation as well as efficacy interpretation.
These entries offer limited information about reported event counts. They do not provide a detailed account of event severity beyond the serious-event category, timing, attribution, or completeness of follow-up. The record does not report further safety analyses.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed, non-randomized crossover study examined salivary cortisol in relation to placebo and CPAP therapy in patients with sleep apnea. It specifies a primary endpoint based on baseline on Day 0 and the average of measurements on Day 1, Day 7 and Day 14, with saliva collected at approximately 7am and 11pm. It also describes sleepiness-related aims and lists additional cortisol outcomes.
It does not establish the direction or magnitude of the primary cortisol result. The primary data and an outcome estimate are not reported in the registry record. There is no reported uncertainty interval or primary test result to show how precisely a change was estimated. The study summary's statements about expected decreases in cortisol, alpha-amylase and sleepiness are expectations, not observed findings.
The record also does not establish whether changes in cortisol corresponded to changes in subjective sleepiness, the Psychomotor Vigilance Test or pupillometry. Although those measures appear in the summary, their results and the methods used to assess their relationships are not reported. The presence of a biological endpoint should not be taken as evidence of a change in symptoms or performance.
Design labels do not resolve limitations in the available evidence. The non-randomized allocation means the arms should not be interpreted as a like-for-like control comparison. The crossover model may allow within-participant comparisons, but treatment sequence, period handling and other relevant analysis details are not reported. The registry also does not describe missing-data methods or a multiplicity approach.
The safety fields record zero serious adverse events, zero other adverse events and zero deaths in each listed group. Those entries are a narrow description of the registry's reported counts, not a complete characterization of safety or evidence that risk is absent.
Overall, the registry record documents the study question and some design and measurement details, but it does not provide the primary outcome result needed to quantify the observed cortisol change. Conclusions about treatment effects or relationships among biomarkers and sleepiness cannot be drawn from the posted record.
13. Why This Trial Matters Statistically
This study is statistically instructive because its endpoint and design are described more clearly than its primary result. Readers can identify a biomarker question, the stated comparison conditions and the planned measurement times, yet cannot evaluate the estimated change because the primary outcome data are not reported in the registry record. This distinction between a defined endpoint and an available result is central to evidence interpretation.
The record also illustrates why a design label is not a substitute for design details. A crossover model can offer the possibility of within-participant comparisons, but those comparisons require attention to period, sequence and carryover. Here, the registry identifies non-randomized allocation and explicitly warns that the arms are not a like-for-like control comparison. Without fuller information about assignment and analysis, readers cannot assume that the design removes systematic differences.
Another statistical lesson is that a biomarker and a patient-relevant measure answer different questions. Salivary cortisol is the primary endpoint; sleepiness and related measures appear in the study summary. A result for one would not automatically establish a result for the others, and an association among measures would not by itself demonstrate that one caused a change in another. The registry does not report the estimates needed to evaluate these questions.
Finally, the record shows why safety counts, outcome estimates and planning calculations must be interpreted separately. Registry entries of zero events do not describe all dimensions of safety, while sample-size planning assumptions are not observed-power results. In the absence of the primary outcome estimate and its precision, the most defensible statistical conclusion is limited: the study's intended question is identifiable, but its primary numerical finding is not available in the registry record.
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 trial-specific limitation is that the registry states that access to the primary data had been lost and that the primary outcome could not be found in the manuscript. It therefore does not report the primary cortisol estimate or its uncertainty. This prevents assessment of the direction, size and precision of the intended endpoint.
The design is listed as non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. The crossover label does not fill in missing details about treatment sequence, assignment, washout, period effects, or carryover. These details are not reported in the registry record, so it is not possible to determine how the study addressed them.
The endpoint description leaves analysis details unspecified. It does not clarify how the morning and evening samples were combined, how the average across later days was calculated, or how within-participant repeated measurements were modeled. The record does not report a statistical analysis plan, confidence intervals, or primary test results.
The registry lists several outcomes and analyses, but does not describe a multiplicity strategy or map each analysis to a specific outcome. It also does not report the number of participants contributing data to each analysis, the extent of missing measurements, the method for handling missing data, or a defined analysis population.
The brief summary mentions salivary alpha-amylase and sleepiness-related measures, but the registry does not report results for these questions. The safety entries record zero events in the listed categories, yet details of event collection and follow-up are not reported. Together, these gaps limit interpretation of both the study's primary question and its broader stated aims.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sleepiness and the Effects of CPAP on Salivary Cortisol and Alpha-Amylase Levels in Patients With Sleep Apnea — NCT01196117.
- Registry record last updated 2020-04-01; status last verified 2020-03.
- Results first posted 2020-04-01.
- 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.
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18. Record Summary
This completed study examined salivary cortisol in patients with sleep apnea in a non-randomized crossover design involving placebo therapy and CPAP therapy. Enrollment is listed as 18, and the intervention periods are described as 14 days. The stated primary endpoint is the difference between baseline on Day 0 and the average of Day 1, Day 7 and Day 14, with saliva collection at approximately 7am and 11pm.
The registry also describes sleepiness-related aims and lists additional cortisol outcomes. It reports that access to the primary data had been lost and that the primary outcome could not be found in the manuscript. No primary cortisol estimate or measure of its precision is reported in the registry record. The record identifies non-randomized allocation and cautions that the arms are not a like-for-like control comparison. Safety entries list zero serious adverse events, zero other adverse events and zero deaths in each group.