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 Impact of Hot Flashes on Sleep and Mood Disturbance (NCT01116401), a na phase 4 study. The primary outcome is Percent Change in Wake After Sleep Onset (WASO).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01116401 |
| Phase | Phase 4 |
| Condition | Menopause, Depression, Hot Flashes |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study planned to enroll premenopausal women. The registry record lists menopause, depression and hot flashes among the conditions. It records enrollment of 29 participants, but does not report further details about the participants or the analysis population.
Intervention
All participants received an injection of leuprolide acetate, a gonadotropin-releasing hormone agonist. The study description says the intervention was intended to induce hot flashes and mimic the menopause transition. Details of the dosing regimen are not reported in the registry record.
Comparator
There was no separate control group in the recorded design. The study is listed as single group, with allocation marked NA and masking listed as none. Baseline measurements are part of the endpoint assessment, but they are not a concurrent control group.
Primary question
The primary outcome was percent change in wake after sleep onset (WASO), comparing baseline with four weeks after injection. WASO measures time spent awake after sleep begins. The registry record does not report the observed percent change or its confidence interval, so the size and precision of the recorded result cannot be described.
The stated scientific aim was to assess the relationship of hot flashes developed in response to leuprolide with sleep disruption and mood changes. Change in the Montgomery-Asberg Depression Rating Scale (MADRS) was listed as a secondary outcome. Since the record does not include outcome estimates, it is not possible to say how sleep or mood changed, or whether any changes tracked the development of hot flashes.
3. Trial Design
This completed Phase 4 study is titled “Impact of Hot Flashes on Sleep and Mood Disturbance.” Massachusetts General Hospital is listed as the sponsor. The registry record lists a start date of 2009-11-03 and a primary completion date of 2011-12-29. Enrollment is recorded as 29.
The design is single group, and all participants were to receive a leuprolide acetate injection. Allocation is marked NA, and masking is listed as none. The record therefore describes no randomized treatment comparison and no separate control arm. Baseline measurements provide a within-participant reference for the primary outcome, but do not supply the same comparison as a concurrent control group.
The study description says that it planned to enroll premenopausal women and use leuprolide-induced hot flashes to mimic the menopause transition. Sleep and mood data were to be collected to assess their relationship to the development of hot flashes. The record does not report additional details about eligibility, recruitment, intervention dose, adherence, or the timing of assessments beyond the primary outcome timeframe.
The primary outcome is percent change in WASO from baseline to four weeks after injection. The secondary outcome is change in MADRS. Two outcome measures and two analyses are recorded, but the details and results of those analyses are not reported in the registry record. A sample-size section on the page contains planning illustrations, which should be read separately from the observed trial design and not as a description of the original protocol. The trial’s own sample-size justification is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | GnRH Agonist Injection |
|---|---|
| STARTED | 29 |
| COMPLETED | 29 |
| NOT COMPLETED | 0 |
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 | GnRH Agonist Injection |
|---|---|---|
| Participants analysed | 29 | |
| Age, Continuous | years | 27.3 (SD 7.2) |
| Sex: Female, Male: Female | Participants | 29 |
| Sex: Female, Male: Male | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change in Wake After Sleep Onset (WASO), measured over baseline and 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is percent change in wake after sleep onset (WASO), assessed at baseline and four weeks after the gonadotropin-releasing hormone agonist injection. The record defines WASO as the average number of minutes spent awake after initiating sleep each night. It uses results from two ambulatory polysomnography studies at baseline and two more conducted four weeks after injection.
In general, WASO is a measure of sleep maintenance: it focuses on wakefulness after sleep has begun rather than on the time it takes to fall asleep. A change in WASO can therefore describe a change in one particular aspect of sleep, not every aspect of sleep quality or overall health. A percent-change endpoint expresses a follow-up value relative to a baseline value, although the registry record does not state the calculation convention or direction used in the analysis.
The registry record identifies a 95% confidence interval as the dispersion measure, but does not report the endpoint estimate or interval limits. It is consequently not possible to describe the magnitude, direction or precision of the observed change. The record also does not state how measurements from the two sleep studies at each time point were combined beyond the averaging description, or how incomplete sleep-study data were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record establishes what the study intended to measure, but does not provide the primary outcome result. In particular, it does not report the percent change in WASO, its 95% confidence interval, or a test result. The planned comparison of baseline with four weeks is clear; the observed change and its statistical precision are not available in the registry record.
That absence matters for interpretation. Without an estimate, one cannot describe whether WASO increased or decreased, how large the change was, or whether the estimate is compatible with a broad or narrow range of values. In general, a confidence interval communicates uncertainty around an estimated effect. Here, the record names the intended interval type but gives no interval values to interpret. A p-value is not reported in the registry record either.
The study aimed to examine sleep and mood in relation to hot flashes developed after leuprolide. However, the record does not provide numerical results for hot flashes, WASO, or MADRS. It therefore does not allow an assessment of the relationship between hot flashes and either sleep disruption or mood change. The secondary outcome is identified as change in MADRS, but its estimate and uncertainty are not reported.
The single-group design is also important. A baseline-to-follow-up comparison describes change over time in the treated group; it does not, on its own, separate change associated with the injection from other changes over the same period. In general, a concurrent control group can help distinguish treatment-related changes from temporal influences, but none is described in this registry record. This design feature limits what a within-group contrast could establish even if the estimate were available.
These points do not determine the direction of the findings. They define what can and cannot be concluded from the material: the record describes a planned assessment and the enrollment, but does not give the outcome data needed to quantify or characterize the result. The listed completion status does not substitute for outcome estimates or a statistical analysis.
9. Statistical Methods Explained
What does the primary endpoint compare?
The primary endpoint compares WASO at baseline with WASO four weeks after the injection. WASO is defined in the record as the average number of minutes spent awake after initiating sleep each night, based on two ambulatory polysomnography studies at each time point. The endpoint is expressed as percent change. In general, a relative-change measure describes the change in relation to a baseline value, while a raw change would describe the absolute difference on the measurement scale. The registry record does not specify the formula or sign convention used for percent change, so the direction should not be inferred from the endpoint title alone.
What does a confidence interval communicate?
The primary outcome lists a 95% confidence interval as its dispersion measure. In general, a confidence interval represents uncertainty around an estimated value under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but an interval can only be interpreted if both the estimate and its limits are available. The record does not report those values. It also does not report a p-value for the primary outcome, so no significance assessment can be described from this record.
What does the single-group design mean?
The study is recorded as single group, with all participants receiving leuprolide. In general, repeated measurements in one group allow a description of within-participant change between time points. They do not provide a randomized comparison with a group that did not receive the intervention. As a result, change from baseline cannot by itself identify which factors caused that change. The registry record gives no separate control arm, and its allocation field is NA.
The baseline assessment is useful as a reference point, but it is not interchangeable with a concurrent control. Differences between baseline and follow-up can reflect the intervention, natural change over time, measurement variability, or other influences. This is a general limitation of before-and-after comparisons, not a claim about what happened in this study.
How should repeated sleep measurements be considered?
The endpoint description refers to two ambulatory polysomnography studies at baseline and two at four weeks. In general, repeated measurements can help characterize a participant’s sleep at a time point, while averaging can summarize multiple observations. The registry record says WASO is calculated by averaging the minutes spent awake after initiating sleep each night. It does not describe whether participant-level values were averaged first, how missing nights or studies were handled, or how variability across the repeated studies entered the analysis. Those details are not reported in the registry record.
What can be said about the analysis plan?
The record lists two outcome measures and two analyses. It names percent change in WASO as the primary outcome and change in MADRS as a secondary outcome. The specific statistical models, hypothesis tests, adjustment variables, confidence-interval procedures, and analysis populations are not reported in the registry record. The record also does not say whether the primary comparison was analyzed using a particular distributional assumption or whether a transformation was considered.
In general, a statistical model is chosen to connect the study question and measurement scale with the structure of the data. For a single-group before-and-after outcome, the analysis needs to account for the fact that repeated observations come from the same participants. The registry record does not identify the method used to do so. No particular model should be attributed to this study without that information.
What role do the planning illustrations play?
The sample-size illustrations on the page are described as planning calculations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are illustrations, not the study’s design: this trial is recorded as single group, not as a two-arm comparison. Such calculations are not observed power and do not show the probability that the completed study detected an effect. The actual numerical planning results are not stated, and the registry record does not report the trial’s own sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and two analyses: the primary percent change in WASO and the secondary change in MADRS. It does not report a multiplicity strategy, such as whether any adjustment was made for examining more than one outcome or analysis. It also does not describe which analysis was designated as primary within any broader family of tests beyond identifying the primary outcome. Consequently, the record does not support an assessment of how multiple statistical comparisons were handled.
Missing-data methods are not reported in the registry record. In particular, it does not say how participants without complete sleep-study measurements or MADRS assessments were handled, whether any values were imputed, or whether analyses used only complete observations. Enrollment is recorded as 29, but the number contributing data to each outcome is not stated. The recorded enrollment should not be assumed to equal the analysis sample for every endpoint.
The analysis populations are also not reported. The registry record does not identify whether the analyses included all enrolled participants, only those with follow-up data, or another defined group. It does not describe exclusions after enrollment or how protocol deviations were treated. These omissions prevent a detailed assessment of the relationship between the enrolled group and the participants included in the outcome analyses.
In general, multiplicity, missing-data handling and analysis-population definitions affect how estimates and uncertainty should be interpreted. They are not reasons to presume a particular bias or analysis choice in this study. They are details that cannot be established from 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 |
|---|---|---|---|
| GnRH Agonist Injection | 0 | 29 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GnRH Agonist Injection | 28 of 29 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GnRH Agonist Injection |
|---|---|---|
| Hot flashes | Blood and lymphatic system disorders | 25 of 29 |
| Spotting | Reproductive system and breast disorders | 12 of 29 |
| Irritability/Mood changes | Psychiatric disorders | 7 of 29 |
| Headache/migraine | Nervous system disorders | 4 of 29 |
| Decreased Sleep/Insomnia | Nervous system disorders | 4 of 29 |
| Decreased appetite | Metabolism and nutrition disorders | 3 of 29 |
| Heavy menstrual bleeding | Reproductive system and breast disorders | 3 of 29 |
| Abdominal cramps | Gastrointestinal disorders | 3 of 29 |
The safety figures list 29 participants at risk for serious adverse events and 0 affected. For other adverse events, the figures list 29 at risk and 28 affected. These are counts in the posted record; they should not be read as measures of the severity, duration, or causal relationship of each event. The record lists no serious-event terms. A null entry for deaths means the death count is not reported in the registry record.
In general, “at risk” identifies the group used as the denominator for a safety count, while “affected” records participants with at least one event in the relevant category. The record does not provide event descriptions for the other adverse events, counts of total events, timing, or judgments about whether events were related to leuprolide. It also does not explain the collection period or the criteria used for event classification.
The safety counts are descriptive. They do not provide a comparison with an untreated or control group, and the record does not support an estimate of how the counts would differ under another intervention. The figures should therefore be read as the adverse-event information recorded for this single group, not as a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The record documents a study designed to examine sleep and mood changes in premenopausal women receiving leuprolide, with the stated aim of assessing their relationship to induced hot flashes. It identifies a primary sleep endpoint, a secondary mood outcome, the planned time points for WASO, and a completed status. It also records enrollment of 29 participants and descriptive adverse-event counts.
What the record does not establish is the numerical result for either outcome. The primary percent change in WASO and its confidence interval are not reported, and the MADRS change is not reported. There are no outcome estimates to characterize as large or small, positive or negative, precise or imprecise. Nor does the record present results that would allow the planned relationship between hot flashes, sleep and mood to be evaluated.
Even if a before-and-after estimate were available, the single-group design would require careful interpretation. In general, an observed change over time is not by itself proof that the intervention caused the change. There is no separate comparator described in this record to help distinguish intervention-related change from other influences. The absence of a comparator is a design limitation, not evidence for or against any particular result.
Accordingly, this page can describe the study structure and the limits of the posted information, but cannot make a claim about whether sleep or mood changed, or what caused any change. The record does not provide enough outcome information to reach those conclusions.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way its design and endpoint frame the question. The primary outcome uses repeated sleep measurements at baseline and four weeks after injection, summarized as percent change in WASO. That endpoint focuses on wakefulness after sleep begins, rather than treating sleep as a single undifferentiated concept. The record also identifies mood change on MADRS as a secondary outcome, reflecting the study’s interest in both sleep and mood.
The single-group structure is equally important. In general, within-participant measurements can describe change over time while avoiding a comparison of unrelated groups. But a baseline reference is not a substitute for a concurrent control group when the question concerns what caused a change. The design should therefore be kept in view when considering any result; in this record, the outcome results are not reported, so no effect estimate can be assessed.
The page also illustrates why the presence of a named endpoint and confidence-interval type is not enough for statistical interpretation. To judge an estimate, readers need its value and uncertainty, along with information about the analysis and the participants contributing data. Those details are not reported in the registry record. Likewise, planning illustrations shown elsewhere on the page should not be confused with observed power or with the original design justification.
The statistical value of the record is thus mainly in its description of the intended measurement and design, and in making clear where the posted information stops. It allows readers to identify the primary question and recognize constraints on causal interpretation, but it does not provide the result needed to quantify the observed sleep or mood changes.
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.
Several trial-specific details needed to evaluate the planned outcomes are not reported in the registry record. The primary WASO estimate and its 95% confidence interval are absent, as is the result for the secondary MADRS outcome. The record therefore does not reveal the direction or magnitude of either outcome change. It also does not provide numerical hot-flash findings, so the stated relationship between hot flashes and sleep or mood cannot be assessed from this information.
The study has no separate control group in the recorded design. A baseline-to-follow-up comparison can describe change in the group, but cannot alone distinguish an intervention-associated change from other influences over time. The record also lists masking as none. Further information about outcome assessment procedures or protections against measurement bias is not reported in the registry record.
Information about participant characteristics, eligibility details, intervention dose, adherence, and outcome-specific analysis populations is not reported. Missing-data procedures, statistical models, covariate adjustments, multiplicity handling, and the trial’s sample-size justification are likewise not reported in the registry record. These omissions limit the ability to assess how robust or generalizable any outcome estimate would be, even though the estimate itself is not available.
Finally, safety reporting is limited to counts of participants affected by serious and other adverse events. The record does not provide descriptions of the other events, their timing, event totals, relatedness assessments, or a reported death count. These limits concern what can be learned from the registry information and should not be mistaken for evidence about unreported outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Impact of Hot Flashes on Sleep and Mood Disturbance — NCT01116401.
- Registry record last updated 2018-01-23; status last verified 2017-12.
- Results first posted 2017-12-26.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed Phase 4, single-group study assessed the planned impact of leuprolide-induced hot flashes on sleep and mood. The registry record lists enrollment of 29, no masking, and no separate comparator. The primary endpoint was percent change in WASO from baseline to four weeks after injection, based on ambulatory polysomnography studies. Change in MADRS was listed as a secondary outcome.
The primary and secondary outcome estimates are not reported in the registry record. The safety figures list 0 of 29 participants affected by serious adverse events and 28 of 29 affected by other adverse events; the death count is not reported. The design and outcome definitions are available, but the posted information does not allow the observed sleep or mood results to be quantified.