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 Pilot Study of Betahistine Dihydrochloride in the Treatment of Major Depression With Atypical Features (NCT00585585), a na phase 2 study. The primary outcome is Maximum Tolerable Dose of Betahistine Dihydrochloride in mg.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00585585 |
| Phase | Phase 2 |
| Condition | Recurrent Major Depressive Disorder With Atypical Features |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with recurrent major depressive disorder with atypical features. The record describes atypical depression as involving temporary mood improvement in response to positive events, alongside features such as increased appetite, increased sleep and severe fatigue. It records enrollment of 1, and says the patient did not complete the study.
Intervention
The intervention was oral betahistine dihydrochloride, with a daily dose range of 50-300 mg. The study description says patients were to be titrated from 50 mg toward a maximum of 300 mg in divided daily doses. The registry does not report the dose actually reached by the patient.
Comparator
There was no comparator arm described. The study used a single-group model, with allocation listed as NA and masking listed as none. Consequently, the record does not offer a like-for-like control comparison that could separate changes during the study from other explanations.
Primary question
The primary outcome was the maximum tolerable betahistine dose, assessed over 7 weeks. The question was whether a dose could be identified as well tolerated during titration, with potential effectiveness mentioned in the study purpose. The patient did not complete the study, and the record says there were not enough data to analyze the primary outcome.
3. Trial Design
This was a Phase 2, single-group pilot study sponsored by the University of Cincinnati. Its official title describes a pilot study of betahistine dihydrochloride in major depression with atypical features. The condition listed is recurrent major depressive disorder with atypical features. The record gives a planned daily dose range of 50-300 mg, administered orally, and describes titration from 50 mg to a maximum of 300 mg in divided doses.
The registry lists allocation as NA, masking as none, and the model as single group. Thus, the design did not include a randomized comparator or a masked comparison. The study status is terminated. Its recorded start is 2007-07 and its primary completion date is 2011-01. The reason for termination is not reported in the registry record.
Enrollment is recorded as 1. This is a pilot design with a very limited recorded enrollment, and the outcome description states that the patient did not complete the study. These registry entries are central to interpreting the record: there is no completed primary-outcome result from which to estimate the maximum tolerable dose. The registry also records no analyses. It does not report a statistical analysis plan, a sample-size justification, an interim-analysis plan, or details about any dose actually received.
Because there was no control group, any change observed during participation could not be interpreted as a comparative treatment effect. In this record, the lack of analyzable endpoint data additionally prevents a description of change within the group. The design and outcome information therefore support a description of the study's question and structure, but not a conclusion about dose tolerability or potential effectiveness.
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: 7 patients signed consent \& 6 patients screen-failed
Overall Study
| Stage | Betahistine Dihydrochloride |
|---|---|
| STARTED | 1 |
| Patients Receiving Drug | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Betahistine Dihydrochloride |
|---|---|
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: The patient did not complete the study and not enough data were collected to be analyzed.
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 | Betahistine Dihydrochloride |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 54 (SD 0) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerable Dose of Betahistine Dihydrochloride in mg, measured over 7 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the maximum tolerable dose of betahistine dihydrochloride, expressed in mg, over 7 weeks. The description defines it as the highest dose that is well tolerated while patients are titrated from 50 mg to a maximum of 300 mg in daily divided doses. This is a dose-finding and tolerability outcome rather than a direct measure of depressive symptoms.
In general, a maximum-tolerated-dose endpoint can help characterize how far dose escalation can proceed under the study's tolerability criteria. It needs an operational definition of what counts as well tolerated and a record of each participant's dose and experience during escalation. The registry description states the general dose range and the aim, but does not report the detailed criteria used to judge tolerability or the dose reached by the patient.
The endpoint is not available as an analyzable result. The registry states that the patient did not complete the study and that not enough data were collected to analyze the outcome. No numerical dose result or summary statistic is reported in the registry record. As a result, the endpoint's intended role can be explained, but its value cannot be interpreted as an observed finding from this study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary endpoint has no analyzable result. The study sought to identify the highest well-tolerated dose during titration over 7 weeks, but the registry says the patient did not complete the study and that the collected data were insufficient for analysis. The record therefore does not establish a maximum tolerable dose. It also does not provide an estimate of potential effectiveness.
Enrollment is recorded as 1, and the registry lists no analyses. These details limit what can be learned from the posted results. There is no reported distribution of doses, no endpoint estimate, and no measure of uncertainty for the primary outcome. It would be misleading to treat the planned dose range as if it were a dose reached, tolerated or evaluated in a completed analysis. The actual dose received is not reported in the registry record.
The design was single group, with allocation listed as NA and masking listed as none. There was no like-for-like control comparison. In general, a control group helps distinguish a treatment-associated change from changes that could occur for other reasons. That comparative interpretation is unavailable in this design; in any case, this registry record does not report an analyzable change in the primary endpoint.
No efficacy result is reported. The study purpose mentions potential effectiveness, but the stated primary outcome concerns dose tolerability. The record does not provide a symptom-scale endpoint, a response definition, or an analysis of depression symptoms. It is therefore not possible to infer symptom improvement or lack of improvement from the registry entry.
The adverse-event counts are limited as well. The record lists one at risk and zero affected for serious adverse events, and one at risk and one affected for other adverse events. These are small counts in a study with enrollment of 1 and should be read as registry counts, not as stable estimates of risk. The death count is not reported in the registry record. The record does not provide detailed event descriptions among the listed serious terms.
General statistical interpretation relies on both an estimated effect and its uncertainty. A confidence interval, when reported, indicates a range of values compatible with the data under the statistical model; it does not repair missing outcome information or create a comparison that the design did not include. No primary-outcome estimate or confidence interval is reported. The appropriate reading is that the registry documents an incomplete pilot study without an analyzable primary endpoint, not a positive or negative finding about tolerability or efficacy.
9. Statistical Methods Explained
The registry identifies a single-group study and reports no analyses. That means there is no reported inferential model or calculated primary-outcome estimate to interpret. The primary endpoint was intended to be the maximum tolerable dose, but the patient did not complete the study and the registry says the available data were insufficient for analysis. The method discussion therefore concerns how such results are generally interpreted, while keeping separate the methods actually documented for this trial.
What does a single-group design tell the reader?
In general, a single-group study can describe outcomes among people who receive an intervention, if outcomes are collected and analyzed. Without a comparator group, it cannot directly estimate how those outcomes differ from what would have happened under another intervention or no intervention. This matters especially for outcomes that can vary over time or depend on clinical judgment. Here, the registry does not report an analyzable primary outcome, so even a within-group dose summary is unavailable.
The design lists no masking. In general, masking can reduce the influence of knowledge about treatment assignment on assessments or reporting, depending on the outcome and study procedures. The record does not describe masking procedures beyond listing masking as none. It also does not report whether dose-tolerability judgments were made using prespecified criteria or by a particular assessor.
How should the dose endpoint be understood?
A maximum-tolerated-dose endpoint is based on escalation and tolerability, not simply on the upper dose permitted by the protocol. In general, the endpoint requires observations during escalation and rules for deciding whether a dose remains tolerable. The registry describes titration from 50 mg to a maximum of 300 mg in daily divided doses and defines the target as the highest well-tolerated dose. It does not report the dose reached, the criteria for dose-limiting effects, or the decision process used to classify a dose. Because the outcome was not analyzed, no dose estimate can be recovered from this record.
The planned range must not be mistaken for an observed range. A dose listed in an intervention description describes the study regimen, not necessarily what a participant received. In this study, the record does not state the actual dose taken. Likewise, a study's stated goal of finding a tolerable dose is not itself evidence that a tolerable dose was identified.
What do estimates and confidence intervals ordinarily add?
In general, an estimate gives a numerical summary of an outcome, while a confidence interval conveys its statistical precision under a model. A narrow interval indicates greater precision than a wide interval, but neither establishes that a result is clinically important or free from bias. An interval also cannot be interpreted when the underlying endpoint has not been estimated. The registry record gives no primary-outcome estimate and no confidence interval.
For a continuous endpoint, a mean or median might summarize observed values; for a binary endpoint, a proportion might be used. Which summary is appropriate depends on the endpoint and analysis plan. The registry does not report a primary analysis method, outcome distribution, or analyzed population. No particular summary should therefore be attributed to this trial.
What do planning calculations mean?
General sample-size calculations ask how much information a future study might need to detect a prespecified effect under stated assumptions. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. It also distinguishes total events for time-to-event calculations from participants per arm for other calculations.
Those assumptions do not describe this single-group study's actual design: the record lists no comparator arm and no like-for-like control comparison. In addition, no analyzable primary effect is reported from which to base a meaningful illustration. A planning calculation is not a result from the trial and is never observed power. Sample-size planning is prospective; it does not turn incomplete observations into evidence or compensate for an endpoint that was not analyzed.
Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. If it is ignored, uncertainty can be understated. The registry does not report an outcome model or data from which over-dispersion could be assessed in this study. Likewise, it does not report an interim-analysis plan, a statistical analysis plan, or a method for handling repeated dose observations. No such methods should be inferred from the title or study objective.
10. Multiplicity, Missing Data and Analysis Populations
The registry reports one outcome measure and no analyses. It does not report a multiplicity plan, a hierarchy of outcomes, or adjustment for multiple comparisons. Multiplicity matters in general when several outcomes, time points, subgroups, or repeated tests are examined: the more opportunities there are to find an unusual result, the more important it becomes to define the analysis strategy in advance. The record does not establish that such testing occurred.
Missing data are directly relevant. The primary-outcome description states that the patient did not complete the study and that not enough data were collected to analyze the outcome. The reason for non-completion and the timing of withdrawal are not reported in the registry record. There is no reported imputation method, sensitivity analysis, or account of how incomplete dose information was handled. With no analyzable primary endpoint, the effect of missingness cannot be evaluated statistically from this record.
The analysis population is also not described beyond the statement about the patient who did not complete the study. The registry does not report an intention-to-treat population, a per-protocol population, or another prespecified analysis set. General analysis-population definitions determine which enrolled participants contribute to a particular estimate; without a reported analysis and population definition, no analyzed denominator or endpoint estimate can be stated.
These omissions do not imply that a particular method was or was not used outside what the registry records. They mean only that the registry record does not report these details, so readers cannot assess the missing-data assumptions, multiplicity control, or population used for an analysis.
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 |
|---|---|---|---|
| Betahistine Dihydrochloride | 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 |
|---|---|
| Betahistine Dihydrochloride | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Betahistine Dihydrochloride |
|---|---|---|
| Mild to Moderate Gastrointestinal irritation | Gastrointestinal disorders | 1 of 1 |
The registry lists the betahistine dihydrochloride group with one at risk and zero affected for serious adverse events. For other adverse events, it lists one at risk and one affected. These are the posted counts; they should not be read as precise estimates of event frequency or as evidence that similar rates would occur in a larger study.
In general, an at-risk count identifies the group included for an adverse-event measure, while an affected count records those meeting that measure. Serious and other adverse events are separate categories, so their counts should not be combined. The registry lists no serious-event terms among its top serious terms. The death count is not reported in the registry record.
The small recorded enrollment, incomplete study participation and absence of detailed analyzed outcomes all constrain interpretation. The entries do not show event timing, duration, severity beyond the serious/non-serious classification, attribution to the intervention, or dose at the time of an event. Those details are not reported in the registry record. The adverse-event counts should therefore be described narrowly as registry counts rather than as a comprehensive safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record documents a pilot study intended to examine the maximum tolerable dose of oral betahistine dihydrochloride in recurrent major depressive disorder with atypical features. It describes a titration range of 50-300 mg per day and a primary endpoint assessed over 7 weeks. The study was terminated, enrollment is recorded as 1, and the patient did not complete the study. The registry states that there were not enough data to analyze the primary outcome.
Accordingly, the record does not identify a maximum tolerable dose. It does not provide an estimate of symptom change, a comparison with a control group, or an estimate of potential effectiveness. The study's stated aim and dose range describe what the investigators sought to examine, not a finding that a particular dose was tolerated or beneficial.
It also does not establish that betahistine is ineffective or intolerable. The absence of an analyzable outcome is not evidence of no effect; it is a limitation on what can be concluded. Likewise, the adverse-event counts are too limited to support a broad safety characterization. They report one at risk and zero affected for serious adverse events, and one at risk and one affected for other adverse events, without detailed event terms or further analysis.
In general, a conclusion about an intervention requires results that correspond to the study question, sufficient information to assess uncertainty, and a design suited to the intended comparison. This record does not report an endpoint estimate, an uncertainty measure, or a comparator. Its contribution is therefore primarily descriptive: it records a planned dose-finding question and an incomplete study, while leaving the central tolerability and effectiveness questions unanswered.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a research question and an analyzable result. The registry describes a focused dose-tolerability objective, a dose-escalation range and a defined timeframe, but reports that the patient did not complete the study and that the primary outcome could not be analyzed. A well-stated endpoint cannot answer its question when the necessary outcome information is unavailable.
It also highlights why the design must shape interpretation. A single-group study without masking or a comparator cannot provide a like-for-like treatment comparison. Even if a within-group outcome had been available, causal interpretation would have been limited by the lack of a control group. In this record, there is no analyzable endpoint on which to make even a descriptive dose estimate.
The entry further shows why planning calculations and observed results are different. General planning calculations depend on assumptions about the design and effect to detect. They are not evidence that an effect was observed, and they are not observed power. A planning setup that assumes equal allocation between two arms does not correspond to the listed single-group design.
Finally, missingness and transparent reporting are part of statistical interpretation, not administrative details. The record identifies non-completion and insufficient primary-outcome data, while leaving the reason and handling of missing information unreported. Readers can distinguish what the trial intended to assess from what the registry can support: no maximum tolerable dose, efficacy estimate, or comparative result is reported.
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 limitations are specific to this record. Enrollment is recorded as 1, and the primary-outcome description says the patient did not complete the study. The registry states that the collected data were insufficient for analysis. Consequently, there is no reported maximum tolerable dose, primary-outcome estimate, or measure of statistical precision.
The design was single group, with allocation listed as NA and masking as none. No like-for-like control comparison is available. The record does not describe the actual dose received, the dose reached, or detailed criteria for deciding whether a dose was well tolerated. Although the stated dose range is 50-300 mg and the endpoint timeframe is 7 weeks, those planned details do not establish what happened during the patient's participation.
The registry does not report the reason for termination or the reason for non-completion. It also does not report a statistical analysis plan, a sample-size justification, interim analyses, a missing-data method, or analysis-population definitions. The lack of reported information prevents assessment of those features; it does not establish what may have occurred outside the registry record.
Safety interpretation is limited by the small recorded counts and absence of detailed event descriptions. The registry lists no serious-event terms among its top serious terms, and the death count is not reported in the registry record. Overall, this record documents the study objective and design, but does not support conclusions about the dose actually tolerated, depressive symptoms, or comparative effectiveness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pilot Study of Betahistine Dihydrochloride in the Treatment of Major Depression With Atypical Features — NCT00585585.
- Registry record last updated 2017-07-25; status last verified 2017-07.
- Results first posted 2017-07-25.
- 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
NCT00585585 is a University of Cincinnati Phase 2 pilot study of oral betahistine dihydrochloride for recurrent major depressive disorder with atypical features. The single-group study had no masking and listed a daily dose range of 50-300 mg. Its primary endpoint was maximum tolerable dose over 7 weeks.
The registry records enrollment of 1 and status as terminated. It states that the patient did not complete the study and that there were not enough data to analyze the primary outcome. No analyses are listed, and no maximum tolerable dose or effectiveness estimate is reported. The reason for termination and the actual dose received are not reported in the registry record.
For safety, the record lists one at risk and zero affected for serious adverse events, and one at risk and one affected for other adverse events. These counts do not provide a broad safety estimate. The main statistical conclusion is that the study's primary question remains unanswered by the analyzable results in the registry.