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 Circadian Effects of Escitalopram (NCT01214044), a na na study. The primary outcome is Change in Dim Light Melatonin Onset.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01214044 |
| Phase | NA |
| Condition | Depression |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oregon Health and Science University |
| Results posted | Yes |
2. Clinical Question
Population
People with depression were eligible for the study. The registry record lists an enrollment of 19. Of the 10 subjects who completed all study procedures, adequate dim light melatonin data from both relevant visits were available for 9 subjects.
Intervention
The intervention is listed as placebo/escitalopram. The visit descriptions show a placebo period followed by escitalopram, with 10 mg daily during Visits 3-5 and 20 mg daily during Visits 6-11.
Comparator
This is a single-group study, with allocation and masking listed as NA and NONE. The registry record does not describe a parallel control group. The placebo period occurred in the study sequence and is not a randomized, like-for-like control comparison.
Primary question
The study asked whether dim light melatonin onset changed from Study Visit 3, after 1 week of placebo, to Study Visit 11, after 8 weeks of escitalopram. It also planned to examine whether circadian resetting was correlated with improvement in depression symptoms.
The primary measure, dim light melatonin onset, is used as a marker of biological time. The registry description defines it as the onset of melatonin secretion under dim light conditions, using thresholds of 10 pg/ml in plasma and 3 pg/ml in saliva. The outcome is a change in timing, reported in decimal military time in hours.
Depression symptom measures and phase angle difference are listed as secondary outcomes. The registry record does not report numerical findings for the primary question or the proposed association between circadian timing and symptom change. It therefore documents the questions and measures, but the posted information does not establish the direction, size, or precision of any effect.
3. Trial Design
This completed study, titled “Circadian Effects of Escitalopram,” was sponsored by Oregon Health and Science University. The record lists a start of 2008-05 and primary completion in 2011-12. It describes a single-group study with 19 participants enrolled. Phase is listed as NA, allocation as NA, and masking as NONE.
The recorded intervention is placebo/escitalopram. The visit descriptions indicate an initial screening and consent period, washout, a placebo period, and then escitalopram treatment. The dose labels identify escitalopram 10 mg daily for Visits 3-5 and 20 mg daily for Visits 6-11. The study description states that participants would have a total of 12 visits over 14-16 weeks, although the available arm description is incomplete.
The primary comparison is within the study sequence: dim light melatonin onset at Visit 3, after 1 week of placebo, compared with Visit 11, after 8 weeks of escitalopram. This sequence does not constitute a randomized comparison between separate treatment groups. In a single-group sequence, changes over time are observed in participants as they proceed through the study; without a concurrent randomized control group, the design cannot separate a treatment effect from other possible influences on change.
The registry lists change in Hamilton Depression Rating Scale scores, change in Beck Depression Inventory II scores, and change in phase angle difference as secondary outcomes. The primary outcome population was smaller than the enrollment: 10 subjects completed all study procedures, and 9 had adequate dim light melatonin data at both visits used for the primary measure. Reasons for incomplete procedures or unavailable measurements are not reported in the registry record.
The record does not report a statistical analysis plan, a sample-size justification, or a detailed protocol for the treatment sequence. The planned study duration and visit descriptions provide context, but do not fill in those missing design details.
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.
Visit 1: Screening and Consent, Washout
| Stage | Study Drug |
|---|---|
| STARTED | 31 |
| COMPLETED | 19 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | Study Drug |
|---|---|
| Withdrawal by Subject | 5 |
| Ineligible | 3 |
| Lost to Follow-up | 4 |
Visit 2: End Washout & Start Placebo
| Stage | Study Drug |
|---|---|
| STARTED | 19 |
| COMPLETED | 17 |
| NOT COMPLETED | 2 |
Visits 3-5: Escitalopram 10 mg Daily
| Stage | Study Drug |
|---|---|
| STARTED | 17 |
| COMPLETED | 14 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Study Drug |
|---|---|
| Withdrawal by Subject | 3 |
Visits 6-11: Escitalopram 20 mg Daily
| Stage | Study Drug |
|---|---|
| STARTED | 14 |
| COMPLETED | 10 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Study Drug |
|---|---|
| Withdrawal by Subject | 3 |
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: Of the 10 subjects who completed all study procedures, adequate dim light melatonin data from both study visits 3 and 11 were available for 9 subjects.
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 | Study Drug |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 50.2 (SD 13.6) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: United States | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Dim Light Melatonin Onset, measured over 8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | decimal military time (hours) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in dim light melatonin onset, or DLMO. The registry describes DLMO as the onset of melatonin secretion under dim light conditions, measured using equivalent thresholds of 10 pg/ml in plasma and 3 pg/ml in saliva. It is expressed in decimal military time in hours and is used as a marker of biological time.
The endpoint compares DLMO at Study Visit 3, after 1 week of placebo, with DLMO at Study Visit 11, after 8 weeks of escitalopram. A change in this measure describes a shift in the timing of the melatonin-onset marker between those visits. It is not, by itself, a measure of depression symptoms; symptom changes are listed separately among the secondary outcomes.
Using a biological-time marker is relevant to the study’s question because the stated aim was to test whether escitalopram resets the body clock and whether that resetting is related to symptom improvement. However, the registry record does not report the numerical DLMO results, including the mean change or its standard deviation. The magnitude and precision of the observed endpoint therefore cannot be described from the posted information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, the timing of the primary measurements, and the number of participants with usable DLMO data. It does not report numerical results for the primary endpoint. In particular, a mean change, standard deviation, confidence interval, and p-value for DLMO change are not reported in the registry record. Without these results, the direction and size of the observed change and the uncertainty around it cannot be assessed.
The primary measure was intended to compare DLMO at Visit 3 with DLMO at Visit 11. The population description states that 10 subjects completed all study procedures and that adequate DLMO data from both visits were available for 9 subjects. This describes the available paired data, but it does not identify the analysis population used for every reported analysis or explain how missing measurements were handled.
The study also intended to test whether improvement in depression symptoms correlated with the degree of circadian resetting. HAM-D scores, BDI-II scores, and phase angle difference appear among the secondary outcomes. The registry record does not report numerical results for these outcomes or the correlations. Thus, the proposed relationship between circadian timing and symptom change cannot be characterized from the posted results.
The single-group sequence is important when interpreting any change that might be reported elsewhere. Participants moved through washout, placebo, and escitalopram periods rather than being assigned to parallel randomized groups. A before-and-after change within a treatment sequence can describe what happened across the visits, but it does not by itself show that the intervention caused that change. Time, study participation, and other influences may also coincide with a change; the record does not describe methods for distinguishing them.
The registry lists 4 outcome measures and 5 analyses, but the analysis details and numerical findings are not reported in the registry record. It is therefore not possible to determine which analysis corresponds to each outcome, whether estimates were adjusted, or how uncertainty was calculated. The appropriate statistical reading is limited: the study registered a measurable within-person question and reports a small number of participants with paired DLMO data, while the posted record does not provide the outcome estimates needed to judge the magnitude or precision of the finding.
9. Statistical Methods Explained
The primary endpoint is a continuous measure of timing. The registry identifies the reported parameter as a mean and the dispersion measure as a standard deviation. A mean describes the central value of a set of measurements; a standard deviation describes how spread out individual measurements are around that mean. Neither statistic alone describes how precisely a study has estimated an average change. The registry record does not report the primary mean change or its standard deviation.
What does a within-person change estimate describe?
For the primary question, each participant with measurements at both visits can contribute a change from Visit 3 to Visit 11. A summary of those paired changes describes the average shift in DLMO across the specified interval among the participants included in the analysis. Pairing is useful because each participant serves as their own reference for the measurement at the earlier visit. It does not create a randomized control group, and it does not by itself establish that the treatment caused the change.
The endpoint timeframe is 8 Weeks: Study Visit 3, after 1 week of placebo, to Study Visit 11, after 8 weeks of escitalopram. The registry describes DLMO in decimal military time and gives examples of the format. A change in time can be interpreted as a change in the timing of the biological marker, but numerical direction and size must be read from the actual estimate. Those results are not reported in the registry record.
What would a confidence interval add?
In general, a confidence interval expresses statistical uncertainty around an estimate. A narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. The interval also helps readers judge which effect sizes remain compatible with the data. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.
A p-value, if reported, would describe how compatible the data are with a specified null hypothesis under the statistical model. It would not measure the size or clinical importance of a change. The registry record does not report a primary-outcome p-value or specify the hypothesis test used. It would be inappropriate to infer the test from the fact that the outcome is continuous or from the study’s objective.
Why does the single-group design matter?
In general, a randomized concurrent comparator can help distinguish treatment-related change from changes that occur over time for other reasons. This record describes a single-group sequence, not a randomized comparison. The placebo period precedes escitalopram in the visit sequence. The record does not describe random assignment between placebo and escitalopram groups, and allocation is listed as NA. The placebo period should therefore not be interpreted as a parallel control arm.
Such a sequence can still provide descriptive information about changes observed during study participation. However, its results are less suited to attributing change specifically to escitalopram than a randomized comparison would be. The registry record does not report additional design features or analysis methods that would address this limitation.
How should planning calculations be read?
In general, sample-size planning asks how many participants would be needed to detect an effect under stated assumptions. The planning illustration associated with this record is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that the original study was designed with those assumptions. The record gives no sample-size justification for the trial, and planning illustrations are not observed power.
The planning description says that non-time-to-event results are expressed as participants per arm, while time-to-event illustrations use total events. This study’s primary outcome is a continuous measure, not a time-to-event endpoint. The numerical planning estimates are not reported in the registry record, and the observed primary effect on which such an illustration would depend is also not reported. Planning figures therefore cannot supply a missing outcome estimate or establish what the study could reliably detect.
The registry lists 4 outcome measures and 5 analyses, but it does not report the statistical model, handling of repeated measurements, covariate adjustment, confidence-interval method, or approach to missing data. These are important method details because they affect how an estimate should be interpreted. General explanations of means, standard deviations, confidence intervals, and p-values do not establish that any particular method was used in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of change in DLMO and secondary outcomes of change in HAM-D scores, BDI-II scores, and phase angle difference. It also reports 4 outcome measures and 5 analyses. The statistical analysis plan and the mapping between the analyses and outcomes are not reported in the registry record.
When a study examines multiple outcomes or performs multiple analyses, the chance of at least one apparently notable result can increase. In general, investigators may specify one primary analysis in advance, use adjustment procedures, or distinguish confirmatory from exploratory analyses. The registry record does not report whether any multiplicity procedure was planned or applied. The listed outcome and analysis counts alone do not reveal how the investigators handled multiple testing.
Missing data are also relevant. The record states that 10 subjects completed all study procedures, while adequate DLMO data from both Visit 3 and Visit 11 were available for 9 subjects. It does not report why other participants did not complete all procedures, why a DLMO measurement was unavailable, or how incomplete outcome data were handled. The record also does not state whether the primary analysis included all participants with paired measurements or used another analysis population.
In general, an analysis restricted to participants with complete measurements may differ from an analysis that includes everyone enrolled, particularly if data availability is related to participant characteristics or outcomes. This is a general concern, not a claim about why data were missing in this study. The registry record does not report sensitivity analyses, imputation, or other methods to assess the effect of missing data.
Without the analysis plan and outcome-level results, it is not possible to assess whether multiplicity or missingness altered the reported estimates. These omissions limit conclusions about the robustness and precision of the findings.
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 |
|---|---|---|---|
| Visit 1: Screening & Consent, Washout | 0 | 31 | 0.0% |
| Visit 2: End Washout & Start Placebo | 0 | 19 | 0.0% |
| Visits 3-5: Escitalopram 10 mg Daily | 0 | 17 | 0.0% |
| Visits 6-11: Escitalopram 20 mg Daily | 1 | 14 | 7.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Visit 1: Screening & Consent, Washout | 0 of 31 |
| Visit 2: End Washout & Start Placebo | 0 of 19 |
| Visits 3-5: Escitalopram 10 mg Daily | 0 of 17 |
| Visits 6-11: Escitalopram 20 mg Daily | 0 of 14 |
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 |
|---|---|
| Visit 1: Screening & Consent, Washout | 0 of 31 |
| Visit 2: End Washout & Start Placebo | 0 of 19 |
| Visits 3-5: Escitalopram 10 mg Daily | 1 of 17 |
| Visits 6-11: Escitalopram 20 mg Daily | 0 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Visit 1: Screening & Consent, Washout | Visit 2: End Washout & Start Placebo | Visits 3-5: Escitalopram 10 mg Daily | Visits 6-11: Escitalopram 20 mg Daily |
|---|---|---|---|---|---|
| suicide attempt | Psychiatric disorders | 0 of 31 | 0 of 19 | 0 of 17 | 1 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Visit 1: Screening & Consent, Washout | Visit 2: End Washout & Start Placebo | Visits 3-5: Escitalopram 10 mg Daily | Visits 6-11: Escitalopram 20 mg Daily |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 0 of 31 | 0 of 19 | 1 of 17 | 0 of 14 |
Serious events with the highest arm-level rate: suicide attempt (7.1%).
The safety record presents adverse-event counts across changing study periods, with the number at risk listed separately for each period. During Visit 1, 31 were at risk, with no serious or other events affected and no deaths listed. At Visit 2, 19 were at risk, again with no affected participants or deaths listed. During Visits 3-5, 17 were at risk; no serious events were listed, 1 participant was affected by an other event, and no deaths were listed. During Visits 6-11, 14 were at risk; 1 participant was affected by a serious event, no other events were listed, and no deaths were listed.
The registry lists “suicide attempt” among the top serious terms at 7.1%. This is a term-level figure in the registry record. The record does not provide a causal assessment in the information, so it should not be read as establishing that escitalopram caused the event.
The risk-group counts vary across visit periods. They describe the participants at risk during each period and should not be added together as if they were distinct groups. The record does not report further detail about event timing within a visit period, severity beyond the serious-event classification, or the investigators’ assessment of relatedness. These counts describe reported events and are not, on their own, a complete evaluation of safety.
12. What the Result Does, and Does Not, Mean
The study addresses a focused biological question: whether DLMO, a marker of biological time, changed from after the placebo period to after 8 weeks of escitalopram. It also set out to examine whether circadian resetting correlated with improvement in depression symptoms. HAM-D scores, BDI-II scores, and phase angle difference are listed as secondary outcomes.
The registry record does not report numerical findings for the primary DLMO outcome, the secondary measures, or the proposed correlations. As a result, it is not possible to state whether the average DLMO shifted, how large any shift was, how variable the measurements were, or how precisely a change was estimated. The record also does not provide the results needed to describe the relationship between symptom change and circadian timing.
Even if a within-person change were available, the study design would matter. The record describes a single-group sequence, with a placebo period followed by escitalopram, and no randomized parallel control group. A measured change across visits would be descriptive evidence about the study participants over that period. Without a suitable concurrent comparator, it would not isolate the effect of escitalopram from other influences that may coincide with time and study participation.
The study’s enrollment was 19, while the primary outcome population description reports 10 subjects completing all study procedures and 9 with adequate DLMO data from both relevant visits. This makes the available primary measurements limited in scope. The record does not explain the missing measurements or report an analysis of how their absence might affect interpretation.
These registry entries do not support a conclusion that escitalopram does or does not reset the body clock, nor do they establish whether such resetting is related to symptom improvement. They describe the intended question, the measurement schedule, and the available data count. The numerical outcome estimates and their uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
Statistically, this study is notable for connecting a biological-time marker with depression symptom measures while using a within-person treatment sequence. DLMO provides a defined timing measure, and the visit schedule identifies the two assessments intended for the primary comparison. The secondary outcomes show that the study also considered symptom scores and phase angle difference.
The design makes it important to distinguish a change observed during treatment from a treatment effect established by comparison. Participants proceeded through the study sequence rather than being assigned to randomized parallel groups. This means the primary question is framed around change within the study, while causal attribution would require more than observing a before-and-after difference.
The distinction between enrollment and usable endpoint data is also central. The registry lists 19 enrolled, 10 completing all study procedures, and 9 with adequate DLMO data at both visits. Statistical estimates can be sensitive to which participants contribute measurements and how missing outcomes are handled. Those analysis details are not reported in the registry record.
Finally, the record illustrates why an outcome definition and study objective are not substitutes for results. The endpoint is described carefully, but its numerical estimate, variability, and uncertainty are not reported. Without those quantities, readers cannot assess the observed magnitude or precision, and the proposed association with symptom improvement remains unanswered in the posted 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.
A central limitation is that the registry record does not report numerical results for the primary endpoint. The mean change in DLMO, standard deviation, confidence interval, and p-value are not reported in the registry record. Numerical findings for the secondary outcomes and proposed correlations are also not reported. This prevents assessment of the direction, magnitude, variability, and precision of the outcomes.
The study is described as single-group, with no randomized parallel comparator identified. The placebo period precedes escitalopram in the study sequence, so it is not a like-for-like control comparison. Changes over time cannot therefore be attributed to treatment from the design description alone.
Only 9 subjects had adequate DLMO data from both visits used for the primary comparison, and the record states that 10 subjects completed all study procedures. The reasons for incomplete procedures or unavailable measurements, and the method used to handle missing data, are not reported in the registry record. The analysis population is not otherwise specified.
The registry lists multiple outcome measures and analyses, but does not report the statistical analysis plan or whether any multiplicity adjustment was used. It also does not report a sample-size justification, detailed modeling approach, or confidence-interval method. The available arm description is incomplete, so additional procedural details cannot be established from the registry record.
Safety counts are reported by study period, but the record does not provide further detail about event relatedness or the investigators’ causal assessments. These limitations constrain both efficacy interpretation and a full appraisal of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Circadian Effects of Escitalopram — NCT01214044.
- Registry record last updated 2019-08-20; status last verified 2019-08.
- Results first posted 2019-08-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The completed study NCT01214044, “Circadian Effects of Escitalopram,” was sponsored by Oregon Health and Science University. The record lists 19 enrolled participants, a start of 2008-05, and primary completion in 2011-12. It is described as a single-group study; allocation is NA and masking is NONE.
The primary outcome was change in DLMO from Visit 3, after 1 week of placebo, to Visit 11, after 8 weeks of escitalopram. The record reports that 10 subjects completed all procedures and 9 had adequate DLMO measurements at both visits. HAM-D scores, BDI-II scores, and phase angle difference are listed as secondary outcomes.
Numerical outcome results and the statistical analysis plan are not reported in the registry record. The record therefore documents the study question and measurement schedule, but does not allow assessment of the size or precision of the primary finding.