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 Adjunctive Isradipine for the Treatment of Bipolar Depression (NCT01784666), a randomized phase 2 study. The primary outcome is Change in MADRS (4 Weeks).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01784666 |
| Phase | Phase 2 |
| Condition | Bipolar Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 2 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with bipolar disorder who were experiencing a major depressive episode and taking lithium, valproate, and/or atypical antipsychotics were the intended population described in the registry record. The enrollment listed in the record is 2. Further eligibility details and a fuller description of the analyzed population are not reported in the registry record.
Intervention
The intervention was isradipine added to ongoing treatment. The record describes an isradipine-isradipine arm in which participants received isradipine during both the first and subsequent 4-week periods.
Comparator
The comparator was placebo, described as an add-on to ongoing treatment. The record also describes placebo non-responders being re-randomized for the subsequent 4-week period, with placebo or isradipine as the possible treatment.
Primary question
The primary question was whether change in depressive symptoms, measured with the Montgomery-Asberg Depression Rating Scale (MADRS), differed between isradipine-treated and placebo-treated periods. The registry record states the hypothesis that isradipine would be superior to placebo, but the posted results do not provide an inferential comparison that answers that question.
3. Trial Design
The registry record identifies this as a randomized, double-masked, parallel-design phase 2 study sponsored by Massachusetts General Hospital. Its status is terminated. The recorded start is 2013-02 and the recorded primary completion is 2014-04. The enrollment is 2.
The intervention and arm descriptions indicate a treatment sequence involving two 4-week periods. The Isradipine-Isradipine arm received isradipine in both periods. The two placebo arm descriptions concern participants who did not respond to placebo during the first period; they describe re-randomization to placebo or isradipine for the subsequent period. These descriptions coexist with the registry's parallel model designation. The record does not explain the relationship between that designation and the treatment sequences in further detail.
The posted outcome entries list a numerical change for the Isradipine-Isradipine and Placebo-Placebo arms. The Placebo-to-Isradipine arm has no participants listed for the outcome. No reason for termination, detailed randomization procedure, masking procedure, treatment dose, adherence information, or fuller protocol description is reported in the registry record. The planned enrollment and rationale for the enrollment are 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 | Isradipine-Isradipine | Placebo -> Isradipine | Placebo-Placebo |
|---|---|---|---|
| STARTED | 1 | 0 | 1 |
| COMPLETED | 1 | 0 | 1 |
| NOT COMPLETED | 0 | 0 | 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 | Isradipine-Isradipine | Placebo -> Isradipine | Placebo-Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 1 | 0 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 0 | 1 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 56 (56 to 56) | — | 44 (44 to 44) | 50 (44 to 56) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 0 | 1 |
| Region of Enrollment: United States | Participants | 1 | 0 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in MADRS (4 Weeks), measured over Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | scores on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in MADRS score over the recorded treatment periods. The MADRS is a scale for depressive symptoms; the registry record says total scores range from 0-60 and that a higher score indicates greater depression severity. The stated assessment is baseline versus week 4, and, for placebo non-responders in the first 4 weeks, week 8 versus week 4.
Change scores describe how a person's recorded score differs between assessments. Because higher MADRS scores indicate more severe symptoms, a negative change represents a lower score at the later assessment than at the earlier one. The registry describes the intended endpoint as change during isradipine-treated epochs versus placebo-treated epochs.
A symptom scale can provide a structured way to quantify change during a trial, rather than relying only on a broad judgment that someone improved or did not improve. However, the record does not report a threshold for clinically meaningful change, the precise handling of repeated treatment periods, or how scores were combined for a treatment comparison. The posted values therefore should not be treated as a complete analysis of the endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted outcome values are -9.0 for the Isradipine-Isradipine arm, with n=1, and 0.0 for the Placebo-Placebo arm, with n=1. The Placebo-to-Isradipine arm has n=0 and no outcome value. On the MADRS, a lower score indicates less depression severity, so the negative value records a lower score at the later assessment in the Isradipine-Isradipine arm; the zero value records no change in the Placebo-Placebo arm. These are descriptive observations from very sparse arm-level data, not a reliable estimate of the difference between treatment strategies.
The record does not provide a standard error, confidence interval, p-value, or adjusted treatment-effect estimate. It also reports no analyses. The posted values therefore do not establish the size or precision of a treatment contrast, and they cannot support a conclusion about whether the registry's stated superiority hypothesis was met. The missing outcome for the Placebo-to-Isradipine arm further limits interpretation of the treatment sequence described in the record.
The endpoint description includes more than one assessment window: baseline to week 4, and week 4 to week 8 for placebo non-responders. The arm summaries alone do not explain how those windows were used to compare isradipine-treated and placebo-treated periods. The registry record does not report the analysis population, method for handling repeated measurements, missing-data approach, or model used for the primary analysis.
Randomization and double masking are features of the stated design, but the presence of those design features does not compensate for the lack of an interpretable comparative estimate in the posted results. With such sparse outcome entries, estimates of variability and uncertainty are especially important, yet they are not reported. The record's displayed values should consequently be read as limited descriptive data, not as a definitive assessment of benefit or lack of benefit.
9. Statistical Methods Explained
Randomization is a design method intended to allocate participants to treatment groups by chance. When implemented as planned, it can reduce systematic differences between groups at the start of a study. Double masking means the record identifies masking of two parties, but it does not name those parties or describe how masking was maintained. Details of sequence generation, allocation concealment, and masking procedures are not reported in the registry record.
The record labels the model parallel, while its arm descriptions also specify treatment sequences and re-randomization of placebo non-responders. A parallel comparison generally assigns participants to treatment groups for comparison across groups. A sequence involving an initial treatment period followed by a new assignment raises additional questions about which period and population form the comparison. The registry record does not report enough analysis detail to resolve those questions. In particular, it does not say whether the primary comparison used only the first period, included later periods, or treated periods as repeated observations within a participant.
The primary endpoint is a change in MADRS score. A change score compares a measurement at a later assessment with a measurement at an earlier assessment. A treatment-effect analysis would ordinarily need to specify how those changes are summarized and compared, and how uncertainty is quantified. The registry record reports numerical values for two arms but no measure of spread, confidence interval, p-value, or model-based contrast. No inferential analysis is posted.
A confidence interval is a general statistical tool for showing the range of effect estimates compatible with the data and the assumptions of an analysis. Its width communicates precision: a wider interval reflects greater uncertainty than a narrower interval. The posted results do not include confidence intervals, so the precision of any treatment difference cannot be assessed from the record. A p-value, when reported, addresses how compatible data are with a specified null model; it is not itself an estimate of effect size or a measure of clinical importance. No p-value is reported for this endpoint.
Sparse data make descriptive values particularly sensitive to the observations contributing to them. With n=1 in each of two arms with reported outcomes, there is no within-arm information in those entries from which to estimate variability. The arm with n=0 has no posted outcome value. These features mean that the displayed arm values cannot stand in for a comparative estimate with quantified uncertainty. This is a limitation of the available result, not a reason to infer an unreported analysis.
The record classifies the endpoint as a count-other outcome and indicates that values are missing or not estimable for a two-arm comparison. It reports one outcome measure and zero analyses. The label does not provide a statistical model, and the registry record does not identify a test or estimator for the primary question. It would therefore be inappropriate to assign a particular method to the sponsor's analysis or to reconstruct one as if it were the prespecified analysis.
Over-dispersion is a general concern when count data vary more than a chosen count model expects; ignoring it can make uncertainty estimates too small. That concept does not establish that an over-dispersion problem occurred in this trial. The record does not describe a fitted count model, a dispersion assessment, or even an inferential analysis for the posted endpoint. The values and endpoint classification alone are not enough to select or evaluate a model.
Planning calculations are different from observed trial results. The stated planning illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such calculations are illustrations based on assumptions; they are not observed power and do not demonstrate that the trial had a particular probability of detecting an effect. No numerical planning estimates are reported in the registry record. The trial's own sample-size justification is not reported in the registry record.
Any recalculation from posted summary values would be an unadjusted calculation, not a substitute for the sponsor's analysis. There is no sponsor analysis posted for comparison in this record, and no recalculated inferential comparison is available. The appropriate reading is therefore limited to the values and counts actually recorded, alongside the explicit absence of a reported comparative analysis.
10. Multiplicity, Missing Data and Analysis Populations
The record lists one primary outcome measure and zero secondary outcomes. It also lists zero analyses. No multiplicity strategy, such as an adjustment for multiple outcomes, time points, or comparisons, is reported in the registry record. The presence of more than one assessment window in the endpoint description does not by itself show how many statistical tests were planned or whether any correction was intended.
The outcome entries are incomplete for a comparison across the described treatment sequences: the Placebo-to-Isradipine arm has n=0 and no value. The record does not explain whether this reflects non-enrollment, missing outcome data, or another reason. A missing-data method, imputation approach, and sensitivity analysis are not reported in the registry record. The record also does not report whether the analysis was based on all randomized participants, participants who completed treatment, or another analysis population.
These omissions matter because the interpretation of a change endpoint can depend on which participants and periods are included, how absent assessments are handled, and which comparison is designated as primary. Those choices cannot be recovered from the posted arm values. No statistical analysis plan or detailed analysis population is reported in the registry record, so no claim about prespecification or analysis conduct can be made from these entries.
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 |
|---|---|---|---|
| Isradipine-Isradipine | 0 | 1 | 0.0% |
| Placebo-Placebo | 0 | 1 | 0.0% |
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 |
|---|---|
| Isradipine-Isradipine | 0 of 1 |
| Placebo -> Isradipine | 0 of 0 |
| Placebo-Placebo | 0 of 1 |
The adverse-event entries report zero serious adverse events among the one participant listed at risk in the Isradipine-Isradipine arm and zero among the one listed at risk in the Placebo-Placebo arm. The Placebo-to-Isradipine arm has zero listed at risk and zero affected. The non-serious adverse-event entries likewise show zero affected among the one participant listed at risk in each of the first two arms, and zero listed at risk in the remaining arm.
These counts describe only what is entered in the registry record. The very sparse recorded groups cannot characterize the frequency or range of possible adverse events, and a zero count does not establish that an event cannot occur. The record does not report death counts. It also does not provide further detail about the observation period, event ascertainment, or the classification of events beyond the serious and other categories shown in the entries. The safety figures should therefore be read as limited recorded counts, not as a comprehensive assessment of safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-masked phase 2 study of adjunctive isradipine was registered for people experiencing bipolar depression, and that the study is now listed as terminated. It also records a MADRS change endpoint and numerical values for two arms. Those details describe the study and its posted results; they do not supply a robust estimate of how isradipine compares with placebo.
The negative MADRS change recorded for the Isradipine-Isradipine arm is consistent with a lower score at the later assessment for the participant represented by that entry. The zero change in the Placebo-Placebo arm records no change for its listed participant. Without a comparative estimate, uncertainty measure, and clear account of how the different periods were analyzed, those values cannot be generalized to the intended population or interpreted as proof of a treatment effect.
Likewise, the sparse adverse-event counts do not show that an intervention is free of risk. They only report that no serious or other adverse events were entered for the participants listed at risk in the two arms with participants. The record does not report death counts or fuller safety details.
The posted results do not explain why the study was terminated, whether enrollment ended as planned, or whether other analyses were conducted outside the registry record. Those matters are not reported in the registry record. The appropriate conclusion is not that treatment succeeded or failed, but that the registry contains too little comparative and uncertainty information to resolve the primary question.
13. Why This Trial Matters Statistically
This trial is statistically notable because its design description and posted outcome entries do not yield a usable comparative result. The study is identified as randomized and double-masked, and the registry describes both an initial treatment period and re-randomization of placebo non-responders. Yet the record provides only sparse arm-level outcome values, no spread estimates, and no inferential analyses. Readers need the analysis method and a treatment contrast to understand what the trial data say about its primary question.
The endpoint's treatment-period structure also illustrates why analysis populations and time windows matter. An outcome measured from baseline to week 4 is not automatically interchangeable with a change from week 4 to week 8. Interpreting a comparison across those periods requires clarity about treatment assignment, response status, and the way repeated observations contribute to the estimate. Those details are not reported in the registry record.
Finally, the record shows why sample size and precision should not be conflated. Planning illustrations are based on stated assumptions and are not observed power. A displayed change value without a measure of uncertainty does not show how precisely the treatment difference is estimated. For this record, the absence of a reported comparative analysis is central to interpretation, not a minor reporting detail.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is the scarcity of posted outcome data: the Isradipine-Isradipine and Placebo-Placebo arms each have n=1, while the Placebo-to-Isradipine arm has n=0. Only the first two arms have numerical outcome values. No variability estimate or inferential comparison is reported, preventing assessment of the size and precision of a treatment contrast.
The registry record does not explain why the study was terminated or whether the listed enrollment reflects the intended enrollment. It does not report the eligibility criteria in detail, treatment dose, adherence, or reasons for the missing arm outcome. These omissions limit understanding of who contributed to the results and how the treatment periods were implemented.
The record designates the study as parallel while describing re-randomization of placebo non-responders. It does not report how the primary analysis handled those sequences or the distinct assessment windows. Analysis populations, missing-data methods, multiplicity handling, and a statistical analysis plan are not reported in the registry record. These gaps prevent reconstruction of the intended treatment comparison and restrict interpretation to the limited descriptive values entered.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Adjunctive Isradipine for the Treatment of Bipolar Depression — NCT01784666.
- Registry record last updated 2017-04-20; status last verified 2017-04.
- Results first posted 2017-04-20.
- 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
NCT01784666 is a randomized, double-masked, parallel-design phase 2 study of adjunctive isradipine for bipolar depression, sponsored by Massachusetts General Hospital. The registry record lists the study as terminated, with start 2013-02, primary completion 2014-04, and enrollment 2.
The primary outcome is change in MADRS score over the recorded treatment periods. The posted values are -9.0 for Isradipine-Isradipine and 0.0 for Placebo-Placebo, each with n=1. The Placebo-to-Isradipine arm has n=0 and no outcome value. No inferential analyses are posted, and the record does not report a comparative estimate or its uncertainty. The adverse-event entries list zero affected in the arms with participants; death counts are not reported in the registry record.