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 Riluzole in the Treatment of Bipolar Depression (NCT00544544), a na na study. The primary outcome is Change in Hamilton Depression Rating Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00544544 |
| Phase | NA |
| Condition | Bipolar Depression |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mclean Hospital |
| Results posted | Yes |
2. Clinical Question
The study asks whether clinical depression symptoms change during treatment with riluzole in people with bipolar depression, and whether clinical response is associated with changes in brain glutamate levels measured by proton magnetic resonance spectroscopy. The registry record identifies the clinical outcome but does not report results for the proposed association with glutamate.
Population
People with bipolar depression. The registry record lists an enrollment of 14; further eligibility details and the characteristics of enrolled participants are not reported in the registry record.
Intervention
Riluzole, with a planned dose schedule beginning at 50 mg twice daily for 2 weeks, followed by increases if tolerated. The record describes a possible increase to 50 mg in the morning and 100 mg in the evening for 1 week, then to 100 mg twice daily for 3 weeks.
Comparator
There is no control group identified. This is a single-group study with masking listed as none, so the clinical question is not a randomized comparison of riluzole with another treatment or with a control condition.
Primary question
What is the change in Hamilton Depression Rating Scale score from baseline (week 0) to week 6 during riluzole treatment? The registry record does not report the mean change or its 95% confidence interval.
3. Trial Design
The registry record describes a completed study of riluzole in bipolar depression, sponsored by Mclean Hospital. The listed start is 2007-06 and primary completion is 2009-06. The study phase is listed as NA. Allocation is also listed as NA, masking as none, and the model as single group. These details indicate that the record does not describe a masked, randomized comparison with a separate control group.
The intervention is riluzole. The arm description gives an initial schedule of 50 mg twice daily for 2 weeks. If tolerated, the dose could be increased to 50 mg in the morning and 100 mg in the evening for 1 week, followed by a further increase to 100 mg twice daily for 3 weeks if tolerated. The record does not report how many participants followed each dose step, whether dose changes occurred, or how adherence was assessed.
The primary outcome is change in Hamilton Depression Rating Scale score over the interval from baseline (week 0) to week 6. Secondary outcomes are the Montgomery Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression Scale. The record lists 4 outcome measures and 4 analyses, but does not report their results or provide details of the analysis methods for each outcome.
Enrollment is listed as 14. The record does not report participant flow, the number contributing data to each outcome, or whether all enrolled participants completed follow-up. It also does not report a control condition, randomization procedure, or blinding. Thus the design can describe symptom measurements during treatment, but does not provide a randomized comparison that separates treatment-associated change from other explanations.
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 | Riluzole |
|---|---|
| STARTED | 14 |
| COMPLETED | 11 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Riluzole |
|---|---|
| Withdrawal by Subject | 1 |
| Adverse Event | 1 |
| Lost to Follow-up | 1 |
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 | Riluzole |
|---|---|---|
| Participants analysed | 14 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 44.5 (SD 12.0) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 7 |
| Region of Enrollment: United States | participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Hamilton Depression Rating Scale, measured over Baseline (week 0) - week 6.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in Hamilton Depression Rating Scale score between baseline (week 0) and week 6. The scale is clinician-rated and measures depression symptom severity using 21 items. Its stated range is from zero to 65, with higher scores indicating more severe depressive symptoms. A change score is intended to describe how the measured symptom burden differs between the beginning and end of the specified interval.
As a general statistical point, a continuous score retains information about the degree of measured change rather than reducing the outcome to categories such as improved or not improved. The mean change summarizes the average change across participants with available measurements. It does not show whether every participant changed in the same direction, nor does it describe the full range of individual responses.
The registry record identifies the endpoint as a mean with a 95% confidence interval, but does not report the mean change or interval. Without those results, the magnitude and precision of the average change cannot be assessed. The record also does not report details such as how missing scale items were handled, whether the score was calculated for every enrolled participant, or the analysis population used.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that the study was completed and identifies a within-group clinical outcome: change in Hamilton Depression Rating Scale score from baseline (week 0) to week 6. It does not report the observed mean change, the 95% confidence interval, or a test result for this endpoint. Consequently, the direction, magnitude, and statistical precision of the primary outcome cannot be described from the registry record.
The study is listed as a single-group model, with allocation listed as NA and masking as none. There is no comparator group. Any change observed between baseline and follow-up would therefore describe change over time among participants receiving the study intervention, rather than a treatment effect estimated against a concurrent control condition. General statistical reasoning is that within-group change can reflect several influences, including the course of the condition, measurement variation, expectations, and other care received. A single-group design cannot distinguish these explanations as a randomized comparison can.
The primary endpoint uses a clinician-rated symptom scale. Its stated range and interpretation provide context for what the score measures, but do not replace the missing outcome estimate. The registry record does not give participant-level results, a distribution of changes, or the number with measurements at both time points. Even if an average were available, a mean alone would not establish that changes were similar across participants.
The study’s stated interest also includes the association between clinical response and change in brain glutamate levels measured by proton magnetic resonance spectroscopy. No result for that association is reported in the registry record. The record likewise names secondary clinical scales, but their outcome estimates are not reported. It is not possible to infer their findings from the description of the planned measures.
The serious adverse event figures list 0 affected among 14 at risk. The record also lists 14 affected among 14 at risk for other adverse events. These figures describe different event categories and should not be conflated. The terms for serious events are not listed, and deaths are not reported in the registry record. The safety figures do not supply evidence about the primary clinical endpoint.
Overall, the available record describes the question, design, outcome definition, dosing schedule, and selected safety counts, but not the primary efficacy estimate. It supports a description of what the study set out to assess, not a conclusion about the amount or certainty of symptom change.
9. Statistical Methods Explained
The registry record identifies the primary outcome as a mean change in a continuous scale and states that the dispersion measure is a 95% confidence interval. It does not report the actual mean, interval limits, or analysis procedure. The explanations below are general statistical context, not a description of unreported methods used by the investigators.
What does a mean change represent?
For a continuous outcome, a mean change is an average of participants’ changes between the specified measurements. In this study, the defined interval runs from baseline (week 0) to week 6. The direction of a change must be interpreted with the scale’s scoring convention: the Hamilton Depression Rating Scale description says higher scores indicate more severe symptoms. However, because the mean change is not reported, its direction cannot be stated.
An average can be useful for describing the central pattern while concealing variation. Some participants might have changes that differ from the average, and the record does not provide a distribution or individual-level results. The mean is also sensitive to unusually large or small observations. Looking at the spread of values and the pattern of individual changes can therefore add context, but those details are not reported in the registry record.
What does a confidence interval communicate?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval’s location conveys which values are compatible with the estimate under the method used. It is not a range that guarantees where every participant’s change lies. Here, the registry record names a 95% confidence interval as the dispersion measure but does not give its endpoints, so its precision cannot be evaluated.
A confidence interval and a significance test address related but distinct questions. A test result alone would not tell readers the size of the estimated change. Conversely, an estimate and interval would help readers judge magnitude and precision even without a binary claim based on a threshold. Neither is available for the primary outcome in the record described.
What can a single-group design estimate?
General statistical interpretation distinguishes a within-group change from a between-group treatment contrast. A single group can be measured at baseline and follow-up, and the difference can describe change over that period. Without a concurrent comparator, however, the analysis cannot directly estimate what would have happened to a comparable group without riluzole. Changes over time may reflect the intervention, natural fluctuation, other influences, or measurement variability. The registry record lists no comparator and no random allocation procedure.
Masking is listed as none. In general, knowledge of treatment assignment may influence behavior, reporting, clinical ratings, or other aspects of measurement. The extent of any such influence in this study is not reported. The outcome is clinician-rated, making the absence of masking relevant to interpretation, but it does not establish that ratings were biased.
Why can variation affect precision?
For continuous outcomes, uncertainty in a mean depends in part on how variable participant measurements are and on how many observations contribute to the estimate. Greater variation generally makes an estimate less precise if other factors are unchanged. This is a general principle, not a finding about this study: the record does not give the variability of score changes or the number with complete primary-outcome data.
For count outcomes, over-dispersion is a general concern when the observed variation is greater than a statistical model assumes. It can make uncertainty estimates too small if the model does not account for the extra variation. That issue is not directly described for this continuous primary endpoint, and the registry record does not report a count-outcome analysis requiring such an interpretation.
How should the planning illustration be understood?
The record describes a planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the illustration is not the trial’s own design. The record does not report the numerical planning outputs or the observed effect used for that illustration.
In general, a sample-size calculation asks how many participants a hypothetical study might need under stated assumptions about an effect, variability, allocation, and statistical threshold. Such an illustration is not evidence that the study had a particular probability of detecting an effect, and it is not observed power. The assumptions described for a hypothetical two-arm comparison should not be mistaken for the actual design of this single-group study. The registry record does not report the protocol’s sample-size justification or a statistical analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 4 outcome measures and 4 analyses. It identifies the Hamilton Depression Rating Scale change from baseline (week 0) to week 6 as the primary outcome and names the Montgomery Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression Scale as secondary outcomes. It does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or how the analyses were selected for reporting. These details are not reported in the registry record.
As general statistical context, assessing multiple outcomes or analyses can increase the chance that at least one result appears notable by chance when each is considered separately. Methods for addressing this issue depend on the analysis plan and the intended interpretation of the outcomes. The record does not provide enough information to say whether or how multiplicity was handled.
Missing-data information is also not reported in the registry record. The record gives an enrollment of 14, but does not state how many participants had baseline and week 6 measurements, whether any observations were missing, or how missing measurements were handled. It does not identify an analysis population, such as all enrolled participants or only participants with observed follow-up measurements. The number enrolled therefore should not be assumed to be the number contributing to each result.
The record does not report interim analyses, a stopping rule, or a statistical analysis plan. These omissions limit assessment of how outcomes and analyses were prespecified and how incomplete data might affect interpretation. No conclusions about those procedures can be drawn from the 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 |
|---|---|---|---|
| Riluzole | 0 | 14 | 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 |
|---|---|
| Riluzole | 14 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Riluzole |
|---|---|---|
| nausea | Gastrointestinal disorders | 6 of 14 |
| headache | Nervous system disorders | 4 of 14 |
| diarrhea | Gastrointestinal disorders | 4 of 14 |
| insomnia | Nervous system disorders | 4 of 14 |
| constipation | Gastrointestinal disorders | 3 of 14 |
| sedation | Nervous system disorders | 3 of 14 |
| neck pain | Musculoskeletal and connective tissue disorders | 3 of 14 |
| dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 14 |
| dizziness | Nervous system disorders | 2 of 14 |
| dry mouth | General disorders | 2 of 14 |
The safety record lists 0 serious adverse events among 14 at risk in the riluzole group. It also lists 14 affected among 14 at risk for other adverse events. These are separate categories in the record: the count for other adverse events should not be read as a serious adverse event count. The listed figures describe event status in the registry record, not the primary depression-scale outcome.
The terms for serious adverse events are not listed. The record does not provide descriptions, severity grades, timing, duration, or assessments of whether events were considered related to riluzole. Deaths are not reported in the registry record. The record also does not specify whether the other adverse events were individual symptoms, event episodes, or another reporting unit, so the listed affected figure should be interpreted using the registry’s category rather than as a detailed event profile.
As general context, safety counts are most informative when read alongside definitions, event descriptions, follow-up duration, and the method of collection. With no control group, these figures do not estimate a comparative risk. The absence of listed serious adverse events is not evidence that no risk exists, and the other adverse event count alone does not establish severity or cause.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed, single-group study of riluzole in bipolar depression. It specifies a primary clinical measure, the Hamilton Depression Rating Scale, and a measurement interval from baseline (week 0) to week 6. It also describes a dose-escalation schedule conditional on tolerability, lists secondary clinical measures, and reports selected adverse event counts.
What the record does not report is the primary mean change or its 95% confidence interval. It therefore does not establish the direction, magnitude, or precision of change in depression symptoms. The record also does not report results for the secondary measures or for the proposed association between clinical response and brain glutamate levels. The study’s stated questions cannot be treated as findings.
Even if a within-group change estimate were available, the single-group design would not provide a randomized comparison with a control condition. General statistical interpretation is that a before-and-after change can describe participants’ measured course, but cannot by itself isolate the effect attributable to the intervention. The absence of masking also matters when considering clinician-rated outcomes, although the record does not show whether ratings were influenced.
The safety counts indicate 0 serious adverse events among 14 at risk and 14 affected among 14 at risk for other adverse events. They do not provide detailed event descriptions or a comparative safety estimate. Deaths are not reported in the registry record.
These limitations do not make the study question unimportant; they define what can responsibly be concluded from the available record. The design and outcome definitions are identifiable, while the central outcome estimates and important analysis details are not. No claim about treatment benefit, lack of benefit, or comparative safety follows from the information reported.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a clinical symptom outcome with an interest in brain glutamate levels. The official title describes an investigation of the association between clinical response and change in brain glutamate levels measured by proton magnetic resonance spectroscopy. This links a clinical measure to a biological measurement, but the registry record does not report the association’s results.
The single-group structure is central to interpretation. It can describe measurements during a period of treatment, but it does not include the randomized comparator needed to distinguish treatment-associated change from change that might otherwise have occurred. This distinction is important whenever baseline and follow-up measurements are interpreted as evidence about an intervention.
The primary outcome is a continuous clinician-rated symptom scale, and its timeframe is explicitly defined. A mean change accompanied by an uncertainty interval could have described both the average pattern and its precision. Those numerical results are not reported in the registry record, so readers cannot judge the size or uncertainty of the primary finding.
The record also illustrates why outcome definitions and outcome results must be distinguished. It names several secondary measures and states the study’s biological question, but a list of planned or identified measures is not evidence of their results. The same applies to the safety categories: the reported counts provide limited descriptive information, but not a comparative estimate or detailed event account.
For biostatistical interpretation, the key lesson is to match claims to design and reporting. A completed study with a defined endpoint is not enough to assess an estimated clinical effect when the estimate and analysis details are absent. The record supplies a framework for asking what was measured, while leaving the main result and its uncertainty unreported.
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 principal limitation for interpreting this trial is that the registry record does not report the primary outcome estimate. Although the endpoint, measurement scale, timeframe, and stated confidence-interval format are identified, the mean change and interval are absent. The clinical magnitude and statistical precision of change therefore cannot be evaluated.
The study is listed as a single-group model, with no comparator identified and masking listed as none. A before-and-after description cannot separate treatment-associated change from other causes of change over time. Because the primary outcome is clinician-rated, absence of masking is also relevant to measurement interpretation, though no rating bias is established by the record.
Important participant and analysis details are not reported in the registry record. These include eligibility criteria, participant characteristics, participant flow, completion of follow-up, outcome-specific analysis populations, missing-data handling, adherence, and dose changes. The dose schedule allows increases if tolerated, but the record does not state how often escalation occurred or how tolerability was assessed.
The registry record lists secondary outcomes and 4 analyses but does not report their estimates, a multiplicity strategy, or a statistical analysis plan. It also does not report results for the stated association between clinical response and glutamate change. The basis for any sample-size justification in the actual trial is not reported in the registry record.
Safety interpretation is limited by the absence of serious-event terms and details of other adverse events. Deaths are not reported in the registry record. These gaps prevent a detailed account of event type, timing, or comparative risk. Together, these reporting limitations mean that the record describes the study’s structure more fully than its clinical findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Riluzole in the Treatment of Bipolar Depression — NCT00544544.
- Registry record last updated 2018-08-07; status last verified 2018-08.
- Results first posted 2010-08-18.
- 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
The registry record describes a completed single-group study of riluzole for bipolar depression, sponsored by Mclean Hospital. Enrollment is listed as 14; the start is listed as 2007-06 and primary completion as 2009-06. Masking is listed as none, allocation as NA, and the study phase as NA.
The intervention schedule begins with riluzole 50 mg twice daily for 2 weeks, with increases if tolerated. The primary outcome is change in Hamilton Depression Rating Scale score from baseline (week 0) to week 6. Secondary outcomes include the Montgomery Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression Scale.
The registry record does not report the primary mean change or 95% confidence interval, secondary outcome results, or results for the proposed association with glutamate levels. The serious adverse event figures are 0 affected among 14 at risk; other adverse events are listed as 14 affected among 14 at risk. Serious-event terms and deaths are not reported in the registry record.