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 Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression (NCT01051440), a randomized phase 4 study. The primary outcome is Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01051440 |
| Phase | Phase 4 |
| Condition | Bipolar Depression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 2 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Steward St. Elizabeth's Medical Center of Boston, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants with bipolar depression were eligible for the study. The primary outcome description says all participants randomized to lisdexamfetamine or placebo were included. The registry records total enrollment of 2.
Intervention
Participants assigned to lisdexamfetamine started at 20 mg per day, with the possibility of increasing to a maximum of 40 mg. The study summary describes treatment alongside a mood stabilizer.
Comparator
The comparison group received placebo for lisdexamfetamine. The study summary also describes placebo as being taken in addition to a mood stabilizer.
Primary question
Did MADRS scores change from baseline to week 8 among participants assigned to lisdexamfetamine, compared with participants assigned to placebo? The registry lists change in MADRS score over time as the primary outcome.
The study was also intended to examine brain responses to affective stimuli and neurotransmitter levels using functional magnetic resonance imaging and magnetic resonance spectroscopy. Its summary describes a further interest in memory and attention, and the registry lists changes in Clinical Global Impressions Severity and Improvement scores as secondary outcomes.
The central clinical question is whether the posted outcome data can distinguish a treatment-associated change from the variation that can occur between participants. With only one participant in each arm, the reported arm values describe those participants; they cannot characterize the range of outcomes in either group. The registry record does not report a statistical comparison or uncertainty interval for the primary outcome. The result therefore cannot establish whether the observed changes represent a consistent difference between treatment strategies.
3. Trial Design
This was a randomized, triple-masked, parallel-group phase 4 study of lisdexamfetamine and placebo for bipolar depression. The registry records enrollment of 2 and a terminated status. The study started in 2010-02, and primary completion is recorded as 2011-06. The reason for termination is not reported in the registry record.
In the lisdexamfetamine arm, participants started with 20 mg per day and could increase to a maximum of 40 mg. The comparator arm received placebo for lisdexamfetamine. The study summary describes both study treatment and placebo as being given in addition to a mood stabilizer. The registry identifies the allocation as randomized, the masking as triple, and the model as parallel. The identities of the masked parties and the practical details of the masking procedures are not reported in the registry record.
The primary outcome was change in Montgomery Asberg Depression Rating Scale score from baseline to week 8. The record also lists change in Clinical Global Impressions Severity and Clinical Global Impressions Improvement scores as secondary outcomes. Brain imaging and spectroscopy were part of the study rationale and aims, but numerical results for those measures are not posted in the registry record.
The primary outcome lists one participant in each arm. Although randomization and masking are features of the design, the enrollment recorded is too limited for the posted arm summaries to characterize outcomes reliably across a broader population. The registry record does not report the planned sample size, a sample-size justification, or details of any recruitment or termination decision beyond the status and enrollment entries.
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 who were not on an approved mood stabilizer (lithium, valproate, or lamotrigine) at the time of enrollment were eligible for a one-month lead in to start a mood stabilizer prior to randomization. Several participants were excluded due to psychiatric co-morbidity, unclear diagnosis, history of stimulant use, or medical concerns.
Overall Study
| Stage | Placebo | Lisdexamfetamine |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants randomized to lisdexamfetamine or placebo were included.
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 | Placebo | Lisdexamfetamine | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 1 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 38 (SD 0) | 30 (SD 0) | 34 (SD 5.7) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time., measured over baseline and 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in Montgomery Asberg Depression Rating Scale (MADRS) score from baseline to week 8. MADRS is a clinician-rated measure comprising 10 items, each rated from 0 to 6, with a maximum total score of 60. Higher scores indicate greater symptom severity. A decrease in score indicates improvement in symptoms, while an increase indicates worsening.
A repeated measure of symptom severity can describe how a participant’s recorded score changes during a study. Comparing change between randomized groups can, in a sufficiently informative trial, help assess whether outcomes differ between treatment strategies while accounting for the starting score. The endpoint’s interpretation depends on the scale’s direction: a negative change represents a lower score at follow-up than at baseline, and a positive change represents a higher score.
The registry reports a mean change of 4.0 in the placebo arm and -22.0 in the lisdexamfetamine arm, with one participant in each arm. These are arm-level summaries based on the posted results. The record reports no dispersion or confidence interval for either mean, and no statistical comparison is posted. With only one participant in each arm, the values cannot show how much individual outcomes vary or how precisely an underlying group difference has been estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a mean change in MADRS score of 4.0 for placebo and -22.0 for lisdexamfetamine. The endpoint description defines decreases as improvement in symptoms and increases as worsening, so the posted values indicate different directions of change for the individual participants represented in the two arms. Each arm contains one participant. These values should therefore be read as descriptions of those observed participants, not as stable estimates of typical outcomes in the treatment groups.
The record does not provide a confidence interval, standard error, or other measure of uncertainty for the arm summaries. It also does not post an inferential comparison for the primary endpoint: the number of analyses recorded is 0, and the registry indicates that values are missing or not estimable for a two-arm comparison for this count-other endpoint. Consequently, the posted results do not establish whether the difference in observed changes reflects a treatment effect, participant-specific variation, or other influences. No treatment conclusion follows from the numerical contrast alone.
The primary endpoint is described as including all participants randomized to lisdexamfetamine or placebo, and the results list one participant per arm. The registry does not provide participant-level scores or additional outcome detail that would allow readers to examine how the change was constructed, whether any observations were missing, or whether there were deviations from the planned measurement schedule.
The study was terminated, with enrollment recorded as 2. The reason for termination is not reported in the registry record. The posted enrollment and results are insufficient to assess whether the study reached a planned target or whether the status reflects a particular operational or scientific decision. The record also does not report the planned sample size or a design justification.
The registry’s stated study aims included clinical symptoms, brain responses to affective stimuli, neurotransmitter levels, and neuropsychological measures. However, the posted numerical primary results concern MADRS change; numerical results for imaging, spectroscopy, memory, or attention are not reported in the registry record. The secondary outcome names are listed, but numerical results for those outcomes are also not included in the posted results.
9. Statistical Methods Explained
General: A randomized parallel-group trial assigns participants to separate treatment groups and compares outcomes between those groups. Random assignment is intended to reduce systematic differences between groups at the outset, while masking can limit the influence of expectations on care, measurement, or reporting. Those design features do not, by themselves, ensure that an estimate will be precise. The amount of information in the results also depends on how many participants contribute usable outcome data and how variable their outcomes are.
For this study, the registry records randomized allocation, triple masking, a parallel model, and one participant in each arm for the primary outcome. The record does not explain who was masked or describe the randomization procedure. With such limited outcome data, design features cannot provide a basis for estimating the range of MADRS changes in either group.
What does the endpoint change represent?
General: A change score expresses the difference between a follow-up measurement and a baseline measurement for the same participant. The sign of the change depends on the scale’s direction and on the subtraction convention. The MADRS description explicitly states that an increase indicates worsening and a decrease indicates improvement. The registry labels the endpoint as change from baseline to week 8 and posts mean changes of 4.0 for placebo and -22.0 for lisdexamfetamine.
A group mean change describes the average change among the participants included in that group. It does not show whether every participant changed by that amount, nor does it show the distribution of individual changes. In this record, each arm has one participant, so the arm mean is based on that participant’s observed change. The posted summaries do not include participant-level data or a measure of variability.
Why does uncertainty matter?
General: An estimate is more informative when its uncertainty is also described. A confidence interval is a range of values compatible with the data under the assumptions of the analysis; it communicates precision as well as the direction of an estimate. A p-value addresses how compatible the observed data are with a specified null model, under the analysis assumptions. Neither is reported for the primary comparison in this registry record.
When data are sparse, an estimate can be highly sensitive to the outcome of a single participant. Without sufficient observations to characterize variation, readers cannot determine whether the observed arm summaries are representative or whether a different set of participants would produce substantially different results. The posted arm means alone do not resolve that uncertainty.
What can a two-group comparison establish?
General: A between-group analysis is intended to estimate how outcomes differ between assigned strategies, with uncertainty reflecting the amount and variability of the data. That estimate is not the same as comparing whether a change within one group is statistically significant and whether a change within the other group is not. A direct comparison is needed to address a treatment-group difference.
The registry does not report an estimable two-arm comparison for this endpoint and records no analyses. It therefore does not provide an adjusted or unadjusted treatment-effect estimate, a confidence interval, or a p-value. No inferential conclusion can be drawn from the arm values alone.
How should planning calculations be read?
General: A sample-size calculation describes how many participants a hypothetical study might need under stated assumptions about the effect to detect, variability, allocation, and statistical method. It is a planning exercise, not a finding about the data already observed. A calculation based on an observed effect is especially uncertain when that observed effect comes from very limited data. Such a calculation is not observed power and does not indicate the probability that the intervention is effective.
The registry record does not report the trial’s own sample-size justification. Any planning illustration based on the observed effect is distinct from the original study design and should not be interpreted as evidence that the trial had adequate information to answer its clinical question.
Why can over-dispersion matter?
General: Over-dispersion occurs when observed variability is greater than a statistical model assumes. If the analysis underestimates variability, its uncertainty estimates can be too narrow and its inferential results too optimistic. For continuous change scores such as MADRS change, the more direct issue is whether the analysis accounts for the actual spread and distribution of participant outcomes. This registry record does not report a dispersion estimate for either arm, so the amount of outcome variability cannot be assessed.
These methodological concepts explain what would ordinarily be needed for a precise group comparison. They do not fill gaps in the registry record: the analysis method, model adjustments, handling of missing observations, and inferential results are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a primary MADRS change outcome and two secondary outcomes: change in Clinical Global Impressions Severity and change in Clinical Global Impressions Improvement scores. The study summary also describes imaging, spectroscopy, memory, and attention as areas of interest. The registry record does not report a multiplicity-control plan or specify how results across the outcomes were intended to be interpreted together. Numerical results for the named secondary outcomes are not reported in the registry record.
Multiplicity matters when many outcomes or analyses are examined because the chance of finding an apparently notable result can increase across repeated tests. General approaches can control that risk by prioritizing outcomes or adjusting inference, but the registry record does not report whether such an approach was planned or used. The absence of posted analyses means there is no basis for assessing the multiplicity of the trial’s reported inferential findings.
The primary outcome description states that all participants randomized to lisdexamfetamine or placebo were included. The posted results list one participant per arm. The record does not give further details about missing outcome observations, withdrawals, exclusions, or the analysis population used for the posted arm summaries. It also does not describe a missing-data method or sensitivity analyses. Missing-data handling should therefore be treated as not reported in the registry record, rather than assumed to be complete or to follow a particular procedure.
The registry records 0 analyses and indicates that a two-arm comparison was not estimable for this count-other endpoint. It does not report an analysis plan, interim analyses, or a protocol for handling multiplicity or missing data. These omissions limit the ability to assess how the posted results were selected and analyzed.
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 |
|---|---|---|---|
| Placebo | 0 | 1 | 0.0% |
| Lisdexamfetamine | 0 | 1 | 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 |
|---|---|
| Placebo | 0 of 1 |
| Lisdexamfetamine | 0 of 1 |
The registry lists 0 serious adverse events among 1 participant at risk in the placebo arm and 0 among 1 participant at risk in the lisdexamfetamine arm. It also lists 0 other adverse events among 1 participant at risk in each arm. These entries mean that no affected participants are recorded in the posted adverse-event counts for the groups shown.
The denominators are very small, so the absence of recorded events in these participants cannot establish that either treatment has no safety risks. The figures describe the recorded experience of the participants enrolled in this study; they cannot characterize uncommon events or provide a reliable estimate of event frequency in a larger population. The registry does not list any serious adverse-event terms. Death counts are not reported in the registry record.
Adverse-event counts also depend on how events were defined, collected, monitored, and reported. Details of those procedures are not reported in the registry record. These entries should therefore be read as a limited description of the posted safety data, not as a comprehensive comparison of safety between treatment groups.
12. What the Result Does, and Does Not, Mean
The posted MADRS results show a mean change of 4.0 in the placebo arm and -22.0 in the lisdexamfetamine arm. Under the scale description, the positive value represents an increase in symptom severity and the negative value represents a decrease. Because one participant is represented in each arm, the results describe those participants’ changes rather than estimating what typically happens in each group.
The registry does not report a statistical comparison, an uncertainty interval, or an analysis method for the primary outcome. It is therefore not possible to determine from the posted summaries whether the difference between the arm values is compatible with a treatment-associated effect or is due to individual variation. The values do not establish that lisdexamfetamine improves symptoms, and they do not establish that it does not.
The study’s randomized and masked design describes how the trial was intended to compare treatment strategies, but the recorded enrollment is only 2 and the status is terminated. Randomization and masking cannot compensate for the limited information in the outcome data. The reason for termination and the planned enrollment target are not reported in the registry record, so the registry entries do not explain why the study ended with the recorded enrollment.
The study summary describes imaging, spectroscopy, and neuropsychological aims, while the registry lists two secondary clinical outcomes. Numerical results for those measures are not reported in the registry record. Their absence means that no conclusion about brain responses, neurotransmitter levels, memory, attention, or the secondary clinical outcomes can be drawn from the posted numerical results.
In short, the record documents a small terminated randomized study and reports individual-level arm changes summarized as means. It does not contain enough outcome information or inferential analysis to support a reliable estimate of a between-group treatment effect. That distinction is about the limits of the posted evidence, not a judgment about the intervention’s clinical value.
13. Why This Trial Matters Statistically
This trial illustrates why a reported direction of change is not the same as an estimated treatment effect. The posted arm means move in different directions, but each is based on one participant. Without enough participants to observe the range of responses, the means cannot show whether those changes are typical or how much they might vary across people with bipolar depression.
It also highlights the role of uncertainty in clinical research. Readers need more than outcome values to assess an intervention: they need a direct comparison and a way to judge the precision of that comparison. The registry does not report an inferential estimate or uncertainty interval for MADRS change, and records that a two-arm comparison was not estimable. The available numbers therefore cannot resolve the study’s primary question.
The study’s planned combination of clinical ratings, imaging, spectroscopy, and neuropsychological testing also illustrates the importance of distinguishing study aims from posted findings. The registry describes these interests, but numerical results for the non-primary measures are not reported in the registry record. A stated objective is not itself evidence that the corresponding outcome changed.
Finally, the terminated status and enrollment of 2 make clear that trial design labels alone do not tell readers how much evidence the completed record contains. Randomization and masking are meaningful design features, but their inferential value depends on usable data and sufficiently informative comparisons. This record is useful for teaching the difference between describing observed participants and drawing conclusions about a broader treatment effect.
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 most direct limitation is the limited enrollment recorded in the registry: 2 participants, with one listed in each arm for the primary outcome. Such sparse data cannot characterize variation in MADRS change between participants or support a reliable estimate of an average treatment-group difference. The posted arm values should not be generalized as representative outcomes for people with bipolar depression.
The primary results do not include dispersion measures, confidence intervals, or a statistical comparison. The registry records 0 analyses and states that a two-arm comparison was not estimable for this endpoint. The analysis method, any covariate adjustment, and the handling of missing observations are not reported in the registry record. These gaps prevent assessment of the precision and robustness of the primary result.
The study status is terminated, but the reason for termination and the planned sample-size target are not reported in the registry record. The record does not provide a sample-size justification, so it is not possible to assess the enrollment against the intended design. It also does not report whether interim analyses were planned or conducted.
The registry describes imaging, spectroscopy, and neuropsychological aims, as well as secondary clinical outcomes, but numerical results for those measures are not reported in the registry record. Adverse-event counts are also based on one participant per arm, and procedural details for collecting and classifying events are not reported. These limitations restrict both efficacy and safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression — NCT01051440.
- Registry record last updated 2013-01-30; status last verified 2012-12.
- Results first posted 2013-01-30.
- 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
NCT01051440 is a randomized, triple-masked, parallel-group phase 4 study of lisdexamfetamine versus placebo for bipolar depression. The registry records enrollment of 2 and status as terminated. The study started in 2010-02, with primary completion recorded as 2011-06; the reason for termination is not reported in the registry record.
The primary outcome is change in MADRS score from baseline to week 8. The posted mean changes are 4.0 for placebo and -22.0 for lisdexamfetamine, with one participant in each arm. No dispersion estimate, confidence interval, or statistical comparison is reported, and the registry indicates that a two-arm comparison was not estimable. The record also lists two secondary clinical outcomes and describes imaging, spectroscopy, and neuropsychological aims, but numerical results for those measures are not reported in the registry record.
Adverse-event entries record 0 serious and 0 other affected participants in each arm, with one participant at risk per arm. These sparse counts do not characterize safety in a broader population.