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 Glucose and Lipid Metabolism on Antipsychotic Medication (NCT00515723), a randomized na study. The primary outcome is DEXA Total Fat.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00515723 |
| Phase | NA |
| Condition | Schizophrenia, Schizoaffective Disorder, Type 2 Diabetes Mellitus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 96 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The primary outcome population is described as a modified Intent to Treat sample with data at week 0, week 6 and week 12. Two Quetiapine participants were excluded from analyses for failure to adhere to the protocol. The broader project description concerns people with schizophrenia who were not diabetic, alongside untreated healthy controls; the primary outcome population is not otherwise characterized in detail.
Intervention
Participants were randomized to flexibly-dosed treatment with olanzapine, risperidone, quetiapine or ziprasidone. The record also describes the broader project as evaluating metabolic effects of selected antipsychotic medications and re-evaluating patients randomized to switch from their current medication.
Comparator
The four medication groups are identified, but the specific primary-outcome comparisons are not reported in the registry record. It is therefore not clear from the record whether each group was compared with another group, whether comparisons were adjusted, or which comparison was treated as primary.
Primary question
The stated hypothesis was that antipsychotic treatment would increase total body fat measured by whole-body DEXA, with larger adverse effects for olanzapine. The primary outcome is DEXA Total Fat, expressed in kilograms of body fat, at baseline, week 6 and week 12. Numerical results for these measurements and comparisons are not reported in the registry record.
The key statistical question is whether total body fat changed over the stated measurement period and whether the observed patterns differed between randomized medication groups. The stated hypothesis gives a direction for the expected change and anticipates a larger effect for olanzapine, but a hypothesis is not a result. Without group estimates, uncertainty intervals or a clearly identified comparison, the registry record does not establish the size or precision of any change or difference.
3. Trial Design
The study is registered as randomized, with no masking and a parallel model. Its listed enrollment is 96. The four intervention groups are olanzapine, risperidone, quetiapine and ziprasidone; each group description says participants were randomized to flexibly-dosed treatment. The phase is listed as not applicable. The registry status is completed.
The primary outcome is DEXA Total Fat. Its stated measurement occasions are baseline, week 6 and week 12. The primary-outcome population is described as a modified Intent to Treat sample with week 0, week 6 and week 12 data. Two participants assigned to quetiapine were excluded from analyses because of failure to adhere to the protocol. The record does not describe additional eligibility rules for this analysis or how participants without all measurement occasions were handled.
The study sits within a broader project that aimed to assess insulin action in skeletal muscle, liver and adipose tissue; body composition; glucose tolerance; and lipid profiles. The project description names stable isotope tracer methods, dual energy x-ray absorptiometry, magnetic resonance imaging and longitudinal metabolic assessments. These aims and methods provide context, but do not establish which analyses were used for the posted primary-outcome comparisons.
The registry record does not state the allocation ratio, sequence generation method, concealment procedure, dose ranges, treatment adherence measures, or detailed visit schedule beyond the primary outcome time points. It also does not identify a single designated comparator for DEXA Total Fat. Consequently, the randomized structure is clear at a high level, while important details needed to reconstruct the comparison and analysis 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.
Before assignment: Participants were enrolled in the study once they signed consent. After enrollment, participants were brought in for a screening visit consisting of a diagnostic interview, screening labs, a review of records and a discussion with their primary psychiatrist. If the patient met all inclusion criteria after screening, study visits were scheduled.
Overall Study
| Stage | Olanzapine | Risperidone | Quetiapine | Ziprasidone |
|---|---|---|---|---|
| STARTED | 25 | 22 | 22 | 27 |
| COMPLETED | 20 | 21 | 21 | 21 |
| NOT COMPLETED | 5 | 1 | 1 | 6 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat (ITT) sample with week 0, week 6 and week 12 data. Two Quetiapine participants were excluded from analyses due to failure to adhere to the protocol.
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 | Olanzapine | Risperidone | Quetiapine | Ziprasidone | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 25 | 22 | 22 | 27 | 96 | |
| Age, Continuous | years | 37.5 (SD 11.2) | 39.2 (SD 11.1) | 36.4 (SD 8.6) | 38.3 (SD 10.2) | 37.9 (SD 10.2) |
| Sex: Female, Male: Female | Participants | 7 | 4 | 9 | 11 | 31 |
| Sex: Female, Male: Male | Participants | 18 | 18 | 13 | 16 | 65 |
| Race/Ethnicity, Customized: White | Participants | 8 | 7 | 4 | 11 | 30 |
| Race/Ethnicity, Customized: Non-White | Participants | 17 | 15 | 17 | 16 | 65 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 0 | 1 | 0 | 1 |
| Body Weight | kilograms | 98.75 (SD 21.04) | 93.88 (SD 19.19) | 92.95 (SD 18.67) | 94.68 (SD 15.90) | 95.16 (SD 18.56) |
| Body Mass Index | kilograms per squared meters | 32.27 (SD 7.38) | 31.04 (SD 6.50) | 31.76 (SD 6.63) | 32.27 (SD 5.56) | 31.87 (SD 6.45) |
| Waist Circumference | centimeters | 108.44 (SD 16.74) | 102.87 (SD 16.66) | 104.10 (SD 15.45) | 108.50 (SD 15.18) | 106.19 (SD 15.95) |
| DEXA Total Fat | kilograms | 32.24 (SD 13.49) | 24.95 (SD 10.07) | 28.69 (SD 11.63) | 31.60 (SD 11.22) | 29.68 (SD 11.89) |
| Whole Body Sensitivity | mg/kg/min | 4.39 (SD 2.16) | 5.53 (SD 3.32) | 5.10 (SD 2.93) | 4.33 (SD 2.01) | 4.79 (SD 2.62) |
6. Primary Endpoint
The registry lists the primary outcome as DEXA Total Fat, measured over The relevant time points include baseline, week 6 and week 12..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | kilograms of body fat |
| Endpoint classification | Continuous Endpoint |
DEXA Total Fat is a continuous measure of total body fat, expressed in kilograms of body fat. Dual energy x-ray absorptiometry estimates body composition, and the registry record identifies whole-body DEXA as the method for measuring this outcome. Total body fat was selected because the study hypothesized that antipsychotic treatment would increase body fat and that the magnitude of the adverse effect would be larger for olanzapine.
Repeated measurement at baseline, week 6 and week 12 allows the study question to concern change over time as well as differences between randomized groups. In general, a continuous outcome preserves information about the amount of change rather than reducing it to a yes-or-no event. A mean can describe the group’s average measurement, while a measure of uncertainty helps show how precisely that mean has been estimated.
The registry lists the outcome parameter as a mean and its dispersion as a standard error, but numerical outcome values are not reported in the registry record. Nor does the record specify the exact contrast used to assess change or between-group differences. The endpoint and its rationale are therefore identifiable, but the magnitude and precision of the observed results cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary outcome and the planned measurement occasions, but does not report numerical results for DEXA Total Fat. Group means, changes from baseline, between-group contrasts, standard errors, confidence intervals and p-values for this outcome are not reported in the registry record. The data therefore do not permit a quantitative assessment of the hypothesized increase in total body fat or the anticipated larger effect for olanzapine.
The four randomized groups are described as olanzapine, risperidone, quetiapine and ziprasidone. However, the specific comparisons used for the primary outcome are not reported in the registry record. A reader cannot tell which groups were directly contrasted, whether changes were analyzed separately at each follow-up or jointly across time, or whether the reported analysis accounted for baseline measurements. No comparison should be inferred from the list of treatment arms alone.
The outcome population requires particular care in interpretation. It is described as a modified Intent to Treat sample with week 0, week 6 and week 12 data, and two quetiapine participants were excluded because of protocol nonadherence. The record does not explain how the requirement for all three measurement occasions affected inclusion, how missing measurements were handled, or whether any other participants were excluded. Thus, the population underlying any numerical result cannot be fully reconstructed from the registry description.
Randomization can support causal comparisons when the assignment process is maintained and the analysis appropriately handles follow-up and exclusions. It does not, by itself, resolve uncertainty arising from missing outcomes, deviations from assigned treatment, or selective reporting of comparisons. Details about allocation procedures, adherence, missing-data methods and the analysis plan are not reported in the registry record.
The posted safety figures list no serious adverse events and no deaths in any of the four groups. These counts describe the registry’s safety reporting, not the primary body-fat endpoint. Other adverse events are also listed, but their detailed terms and severity are not posted beyond the aggregate counts shown in the record. None of these safety counts substitute for estimates of change in DEXA Total Fat.
Overall, the registry record supports a description of the study question, randomized groups and outcome schedule, but not a conclusion about the direction, size or statistical precision of the primary outcome findings. An absent numerical result is not evidence of no change or no between-group difference.
9. Statistical Methods Explained
What does a mean describe?
For a continuous outcome such as DEXA Total Fat, a group mean describes the average measured body-fat value among participants included in the analysis. A comparison of means can describe the average difference between groups or between measurement occasions, depending on the estimand and model. The registry identifies a mean as the outcome parameter, but it does not give the mean values or specify the exact primary contrast.
A mean is only one part of an analysis. The estimate needs to be interpreted alongside its uncertainty and the design of the comparison. In a repeated-measures study, values from the same participant are related; an analysis that treats them as independent would not reflect that structure. This is a general statistical consideration, not a statement about the method used in this study. The analysis method is not reported in the registry record.
What does a standard error convey?
The registry lists standard error as the measure of dispersion for the primary outcome. In general, a standard error describes the estimated precision of a statistic, such as a mean. It is not the same as the spread of individual participant measurements. A standard error is useful for understanding uncertainty in an estimate, but it does not by itself show the range of participant values.
A confidence interval is a range of values produced by a statistical procedure that, under its assumptions, expresses uncertainty about an estimate. Its width reflects precision: a narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry record does not report confidence intervals for DEXA Total Fat, so the precision of the primary outcome estimates cannot be assessed from that record.
Why does the comparison matter?
A treatment effect is defined by a contrast: for example, a difference between assigned groups, or a difference in change from baseline between groups. Different contrasts answer different questions. A within-group change does not by itself show that the change differs from what occurred in another randomized group. The specific primary-outcome contrasts are not reported in the registry record, so the treatment effect targeted by the reported analyses cannot be identified with confidence.
In general, baseline measurements can be incorporated in different ways, including analysis of follow-up values adjusted for baseline or analysis of change from baseline. These approaches may produce different estimates and rely on different modeling choices. The registry record does not identify which approach was used. It also does not report whether the repeated observations were modeled jointly, how correlation within a participant was handled, or what assumptions underpinned the analysis.
What can a p-value establish?
In general, a p-value measures how compatible the observed data are with a specified statistical model and null hypothesis, under the assumptions of that analysis. It does not measure the probability that the null hypothesis is true, the probability that a finding will replicate, or the clinical importance of an estimated difference. Interpretation also depends on the chosen contrast, analysis population and any multiplicity from testing multiple outcomes, time points or groups.
Numerical p-values for the primary outcome are not reported in the registry record. It is therefore not possible to assess the statistical evidence for the stated hypothesis from the registry description. Even if a p-value were available, the estimated magnitude and confidence interval would still be important for understanding the size and precision of the result.
How should planning illustrations be understood?
In general, sample-size planning uses assumptions about the effect to be detected, variability, significance level, allocation and statistical model. A planning illustration based on an observed effect is not a record of the trial’s original design justification and does not show the probability that the completed study detected an effect. The registry record explicitly describes its planning illustration as computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The effect to detect is described as a stated fraction of the observed effect.
Those assumptions are illustrations, not evidence that the study was originally designed around them. The trial’s own sample-size justification is not reported in the registry record. The illustrations should not be read as observed power or as a substitute for the observed estimates and their uncertainty. No sample-size values for the primary outcome are reported in the registry record’s narrative information.
What remains unknown about the analysis?
The record does not describe the statistical model, baseline adjustment, treatment of repeated observations, missing-data assumptions, outlier handling, covariate adjustment or model diagnostics. It does not report whether analyses followed an intention-to-treat principle, how the modified population was formed beyond the stated time-point data requirement, or whether the four analyses correspond to particular outcomes or comparisons. These omissions limit reproducibility and make it difficult to judge whether the statistical analysis matches the randomized design.
General statistical explanations describe how methods can be interpreted; they do not establish that a particular method was used. Without numerical estimates and a fuller account of the analysis, the registry record permits a description of the study framework, but not a detailed statistical appraisal of its primary result.
10. Multiplicity, Missing Data and Analysis Populations
The study description includes several scientific aims, multiple metabolic and body-composition measures, and repeated assessments over time. The primary outcome itself has three stated measurement occasions. When many outcomes, time points or group comparisons are examined, the chance of a nominally unusual result arising by chance can increase. In general, a prespecified analysis hierarchy or multiplicity adjustment can help clarify how multiple tests are interpreted.
The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or which primary-outcome contrast was designated for inference. It also does not describe interim analyses or a statistical analysis plan. These details are not reported in the registry record, and should not be inferred from the number of analyses listed.
The primary outcome population is described as modified Intent to Treat and includes participants with week 0, week 6 and week 12 data. Two quetiapine participants were excluded because of failure to adhere to the protocol. The record does not explain how missing measurements were handled, whether participants lacking any of the specified occasions were excluded, or whether another method was used to retain partial records. The reasons for any other missing data are not reported in the registry record.
These issues matter because exclusions and missing follow-up can affect which participants contribute to an estimate. A complete-case analysis, imputation approach or model using available observations would make different assumptions. This is a general point; the registry record does not identify which approach was used. The available description is therefore insufficient to determine the impact of missing data, protocol deviations or multiple comparisons on the primary-outcome inference.
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 |
|---|---|---|---|
| Olanzapine | 0 | 19 | 0.0% |
| Risperidone | 0 | 21 | 0.0% |
| Quetiapine | 0 | 20 | 0.0% |
| Ziprasidone | 0 | 21 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Olanzapine | 0 of 19 |
| Risperidone | 0 of 21 |
| Quetiapine | 0 of 20 |
| Ziprasidone | 0 of 21 |
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 |
|---|---|
| Olanzapine | 13 of 19 |
| Risperidone | 8 of 21 |
| Quetiapine | 9 of 20 |
| Ziprasidone | 11 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Olanzapine | Risperidone | Quetiapine | Ziprasidone |
|---|---|---|---|---|---|
| Drowsiness/Somnolence | Psychiatric disorders | 9 of 19 | 3 of 21 | 5 of 20 | 6 of 21 |
| Tiredness/Fatigue | Psychiatric disorders | 8 of 19 | 4 of 21 | 4 of 20 | 4 of 21 |
| Hunger | Psychiatric disorders | 5 of 19 | 3 of 21 | 3 of 20 | 2 of 21 |
| Anxiety | Psychiatric disorders | 1 of 19 | 2 of 21 | 2 of 20 | 2 of 21 |
| Restlessness | Psychiatric disorders | 1 of 19 | 1 of 21 | 1 of 20 | 3 of 21 |
| Headache | Psychiatric disorders | 1 of 19 | 1 of 21 | 3 of 20 | 0 of 21 |
| Difficulty Concentrating | Psychiatric disorders | 0 of 19 | 0 of 21 | 0 of 20 | 3 of 21 |
| Tremor | Psychiatric disorders | 0 of 19 | 0 of 21 | 0 of 20 | 3 of 21 |
The registry lists serious adverse event counts for each randomized medication group. For olanzapine, the record lists 0 serious events among 19 participants at risk; for risperidone, 0 among 21; for quetiapine, 0 among 20; and for ziprasidone, 0 among 21. Deaths are listed as 0 in all four groups. These are counts in the registry record, not estimates of comparative risk.
The record also lists other adverse events affecting 13 olanzapine participants, 8 risperidone participants, 9 quetiapine participants and 11 ziprasidone participants. These are separate from the serious-event counts. The registry does not provide event-level descriptions for these other adverse events in the information available for this summary.
Zero recorded serious events should be read as no events listed in these groups, not as proof that serious events cannot occur or that the groups have identical safety. The record does not state the safety observation period, event definitions, completeness of follow-up, or a comparative safety analysis. Without those details and uncertainty estimates, the counts cannot establish precise differences between medications.
12. What the Result Does, and Does Not, Mean
The study addresses an important measurement question: whether total body fat, assessed by DEXA, changed during treatment with selected antipsychotic medications and whether the pattern differed across randomized groups. The registry also states a specific hypothesis that treatment would increase total body fat, with larger adverse effects for olanzapine. This makes the study question clear, but does not establish what the measurements showed.
The registry record does not report the primary outcome’s group means, changes, contrasts, standard errors, confidence intervals or p-values. It therefore does not support a quantitative conclusion about the presence, direction, size or precision of any treatment-associated change. The absence of these results must not be interpreted as evidence that no change occurred, nor as evidence that the stated hypothesis was confirmed.
The randomized parallel structure is relevant to comparisons between assigned treatment groups. However, the specific primary comparison and the analysis method are not reported in the registry record. The outcome population also excludes two quetiapine participants for protocol nonadherence and is defined by having data at the stated measurement occasions. The consequences of these features for the estimates cannot be assessed from the available record.
The primary outcome is one part of a broader project focused on metabolic function, body composition, glucose tolerance and lipid profiles. Findings from DEXA Total Fat, if fully reported, would address that body-composition measure over the stated follow-up period. They would not by themselves establish effects on insulin action, glucose tolerance, lipid profiles or long-term cardiovascular consequences. Those are distinct questions requiring their own estimates and appropriate follow-up.
The safety counts likewise have a limited interpretation. They describe listed serious and other adverse events in the four groups, but do not provide a comparative safety estimate or detailed event timing. Overall, the record describes the research question and design more fully than it reports the primary outcome findings. Statistical interpretation must remain correspondingly limited.
13. Why This Trial Matters Statistically
This trial is statistically notable for asking a longitudinal question about a continuous body-composition measure within a randomized, parallel-group study. Repeated DEXA measurements at baseline, week 6 and week 12 can, in principle, describe both change over time and differences in change across treatment groups. A clear distinction between within-group change and between-group contrast is essential to interpreting such a design.
The stated hypothesis also anticipates a larger adverse effect for olanzapine. That directional expectation makes the choice and prespecification of comparisons important. The record identifies four randomized medication groups but does not report which contrasts were primary or how multiple groups and time points were handled. Without that information, the statistical target of the primary analysis is not fully specified.
The modified Intent to Treat population highlights another common issue in clinical-trial interpretation: the analysis population may differ from the set of randomized participants. The exclusion of two quetiapine participants for protocol nonadherence and the requirement for measurements at three occasions raise questions about missing follow-up and deviations from assigned treatment. The registry record does not provide enough detail to determine how these issues were addressed.
The broader project description includes multiple metabolic and body-composition aims. This makes transparent reporting of outcome-specific estimates, uncertainty and multiplicity procedures especially valuable. The registry record’s lack of numerical primary-outcome results prevents readers from judging the magnitude and precision of the findings, regardless of the conceptual relevance of the question.
These considerations illustrate why a randomized label alone is not enough for full statistical interpretation. The comparison, analysis population, handling of repeated observations, missing-data strategy and uncertainty around estimates all contribute to what a result can support. In this record, several of those elements are not reported, limiting independent assessment.
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 limitation for interpreting the primary endpoint is the absence of numerical outcome results in the registry record. No group-level DEXA Total Fat estimates, changes, treatment contrasts, standard errors, confidence intervals or p-values are included in the available information. This prevents assessment of effect magnitude and precision.
The primary comparison is not identified. Although the registry lists four randomized medication groups, it does not state which pair or set of groups formed the primary contrast, whether the central question concerned change from baseline, or how the three measurement occasions entered the analysis. The statistical model and any baseline adjustment are also not reported.
The analysis population is described as modified Intent to Treat, requiring week 0, week 6 and week 12 data. Two quetiapine participants were excluded for failure to adhere to the protocol. The record does not give a complete flow of participants through randomization, follow-up and analysis, or explain the treatment of other missing measurements and deviations. This makes the analyzed population difficult to reconstruct.
Other limitations of interpretation include the absence of reported details on allocation procedures, concealment, adherence, dose ranges, multiplicity, interim analyses and the statistical analysis plan. The safety record does not specify the observation period or event definitions. The trial’s sample-size justification is not reported in the registry record.
The project description spans several metabolic and body-composition aims, while the primary outcome is total body fat measured by DEXA. Any interpretation should remain specific to that endpoint and its stated follow-up. The registry record does not provide enough information to infer results for the other aims or longer-term consequences.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Glucose and Lipid Metabolism on Antipsychotic Medication — NCT00515723.
- Registry record last updated 2019-10-02; status last verified 2019-10.
- Results first posted 2019-10-02.
- 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
NCT00515723, titled “Glucose and Lipid Metabolism on Antipsychotic Medication,” is listed as a completed, randomized, unmasked, parallel study with enrollment of 96. The four described randomized groups received flexibly-dosed olanzapine, risperidone, quetiapine or ziprasidone.
The primary outcome is DEXA Total Fat, measured in kilograms of body fat at baseline, week 6 and week 12. The stated hypothesis anticipated an increase in total body fat during antipsychotic treatment, with larger adverse effects for olanzapine. The analysis population is described as modified Intent to Treat with data at all three occasions; two quetiapine participants were excluded for protocol nonadherence.
Numerical results for the primary outcome and the precise comparisons are not reported in the registry record. Serious adverse events and deaths are listed as zero in each group. The record does not provide the statistical analysis plan, missing-data methods, multiplicity approach or detailed safety observation period.