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 L-arginine in Treatment as Usual in Schizophrenia (NCT00718510), a randomized na study. The primary outcome is Change From Baseline in Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00718510 |
| Phase | NA |
| Condition | Schizophrenia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Alberta |
| Results posted | Yes |
2. Clinical Question
Population
Patients diagnosed with schizophrenia or schizoaffective disorder using DSM-IV criteria. The registry reports enrollment of 13 participants; the study description anticipated 14.
Intervention
L-arginine added to treatment as usual. The planned dose was 3 grams twice a day, for a total daily dose of 6 grams, during an active treatment period of 3 weeks.
Comparator
Placebo added to treatment as usual. Participants were assigned to receive L-arginine and placebo in opposite orders, with a 5-day wash-out between the treatment periods.
Primary question
Whether PANSS total and subscale scores changed from baseline during the 3-week treatment period, comparing adjunctive L-arginine with adjunctive placebo. The registry record does not report the outcome values or a treatment-effect estimate.
The study was designed to examine whether adding L-arginine to treatment as usual could affect schizophrenia symptom measures. Its primary outcome covered the PANSS total score and the positive, negative, and general psychopathology subscales. The record also lists change in the Clinical Global Impression scale and the Calgary Depression Scale for Schizophrenia as secondary outcomes.
The crossover design means that participants were intended to receive both study conditions, one after the other. One sequence began with L-arginine and then switched to placebo; the other began with placebo and then switched to L-arginine. Treatment as usual was part of both conditions. This allows within-participant comparisons in principle, but the registry record does not report the observed measurements or a comparison of the two conditions.
Consequently, the clinical question is identifiable from the planned outcomes, but its answer is not available in the registry record. The available information describes what the investigators intended to measure, not whether scores changed or how the conditions differed.
3. Trial Design
This was a randomized, double-blind, quadruple-masked, placebo-controlled crossover study of L-arginine as an adjunct to treatment as usual in schizophrenia. The registry identifies the sponsor as the University of Alberta. It records the study as completed, with 13 participants enrolled. The study description anticipated 14 participants, a distinction between the expected and recorded enrollment.
Participants were assigned to one of two treatment sequences: L-arginine first followed by placebo, or placebo first followed by L-arginine. Both conditions were added to treatment as usual. The planned active treatment duration was 3 weeks for each condition, separated by a 5-day wash-out. The registry descriptions of the sequences are truncated, so any further details beyond the stated design and schedule are not reported in the registry record.
The study description identifies baseline and weekly assessments during the first treatment period, a wash-out assessment, and assessments during the second treatment period. It describes the first active period as 3 weeks and the second as 3 weeks. The registry lists the primary PANSS timeframe as baseline and 3 weeks. It does not clarify in the posted results how the primary timeframe was applied across both treatment periods.
The registry records the study start as 2009-09 and primary completion as 2011-07. The phase is listed as not applicable. These design details establish the intended structure, but do not show whether the schedule was followed by every participant, how many participants completed each period, or whether sequence groups remained balanced.
A crossover comparison can account for stable differences between participants because each participant receives both conditions. Its interpretation also depends on the conduct and analysis of the treatment periods. The registry record does not report period-specific results, sequence effects, carryover assessments, or participant flow through the two sequences.
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.
First Intervention (3 Weeks)
| Stage | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second |
|---|---|---|
| STARTED | 7 | 8 |
| Received Intervention | 7 | 7 |
| COMPLETED | 7 | 7 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
Washout (5 Days)
| Stage | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second |
|---|---|---|
| STARTED | 7 | 7 |
| COMPLETED | 7 | 7 |
| NOT COMPLETED | 0 | 0 |
Second Intervention (3 Weeks)
| Stage | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second |
|---|---|---|
| STARTED | 7 | 7 |
| COMPLETED | 6 | 7 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who received all doses of each intervention and completed all study visits were included in the efficacy analysis
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 | L-arginine Treatment First, Placebo Treatment Second | Placebo Treatment First, L-arginine Treatment Second | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 7 | 13 | |
| Age, Continuous | years | 33.8 (SD 15.1) | 37.8 (SD 8.1) | 36 (SD 11.5) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 5 | 7 | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks, measured over Baseline and 3 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in mean PANSS total score and the positive, negative, and general psychopathology subscale scores at 3 weeks. PANSS is a 30-item instrument used to assess schizophrenia symptoms. Each item is rated on a 7-point scale, from absent to extreme. The total score ranges from 30 to 210, with higher scores indicating greater symptom severity. The positive and negative subscales each contain 7 items and range from 7 to 49; the general psychopathology subscale contains 16 items and ranges from 16 to 112. Higher subscale scores likewise represent greater severity.
Using a standardized symptom scale allows investigators to describe symptom burden consistently and to compare measurements over time. A change-from-baseline outcome focuses on how the measured score differs from the participant’s starting score, rather than treating the follow-up score in isolation. The registry also lists the mean and standard deviation as the outcome summary measures.
The primary outcome includes multiple related scores rather than one single score: the total and three subscales. The registry record does not report their observed means, changes, standard deviations, confidence intervals, or treatment comparisons. Thus, the endpoint’s intended meaning is clear, but the magnitude and precision of any observed changes cannot be judged from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a trial intended to compare L-arginine with placebo, both added to treatment as usual, using a crossover design. It reports the planned primary outcome and the study’s enrollment, but it does not report numerical results for the PANSS outcomes. Without those measurements or a treatment-effect estimate, the direction, size, and precision of any difference between conditions are unknown from the record.
This absence is important when reading any statistical display associated with the record. A planning calculation, a plot of assumed effects, or a sample-size illustration is not an observed trial result. The record’s stated sample-size assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such assumptions can illustrate planning scenarios; they cannot establish what happened among participants. The registry does not report the trial’s own sample-size justification, and no observed-effect estimate is available to interpret.
The crossover structure potentially allows comparison of each participant’s measurements under both conditions. That feature does not remove all uncertainty. The statistical interpretation would depend on which participants completed both periods, the handling of period and sequence, and whether effects from the first condition could persist into the next. The record describes a wash-out period but does not report tests or analyses addressing period, sequence, or carryover effects.
The record lists enrollment of 13 and an expected total of 14. Enrollment alone does not establish how many participants contributed to each outcome or completed both treatment periods. The specified efficacy population included participants who received all doses of each intervention and completed all study visits. The number meeting that criterion, and the handling of participants who did not, are not reported in the registry record.
The secondary outcomes are changes in the Clinical Global Impression scale and Calgary Depression Scale for Schizophrenia at 3 weeks. Numerical results for these measures are also not reported in the registry record. The record therefore does not permit assessment of consistency across symptom measures or of the uncertainty around any secondary comparison.
Overall, the registry supports conclusions about the trial’s planned question and design, not about the comparative outcomes. It is not possible from these entries to determine whether scores differed between conditions, whether any difference was clinically meaningful, or how precisely an effect was estimated. Absence of posted efficacy results should not be interpreted as evidence of either benefit or lack of benefit.
9. Statistical Methods Explained
The registry describes the planned analysis as an analysis of variance of outcome measures, with treatment as a between-subject factor and pre- and post-treatment scores as within-subject factors. This wording describes a model for comparing measurements across treatment conditions and time. The record does not report a fuller statistical analysis plan, the exact model specification, or the analysis results.
What a mean and standard deviation describe
A mean summarizes the average score in a group or condition. A standard deviation describes how spread out individual scores are around that average. They answer different questions: the mean concerns the central value, while the standard deviation describes participant-to-participant variability. Neither alone shows how precisely a treatment contrast is estimated. Precision depends on the design, the number of usable observations, and the variability of the relevant differences.
For a continuous outcome such as a scale score, a treatment comparison may be expressed as a difference in mean change or as a model-based contrast. A confidence interval around a contrast would show a range of values compatible with the data and model, with wider intervals indicating less precision. The registry record does not report a contrast or confidence interval for the primary or secondary outcomes, so these features cannot be evaluated for this trial.
How crossover comparisons differ
In a crossover design, participants receive more than one condition in sequence. Each participant can therefore contribute measurements under both conditions. Comparing measurements within the same participant can account for stable characteristics that might otherwise make groups differ. However, the analysis must also consider that observations from the same participant are related, and that the conditions occur in different periods and sequences.
The registry’s brief analysis description refers to treatment as a between-subject factor and pre- and post-treatment scores as within-subject factors. It does not explain how this proposed analysis represents the crossover sequence or within-participant dependence across both treatment periods. It also does not state whether the first-period data would be analyzed separately, how period effects would be handled, or whether carryover was assessed. These are not details that can be inferred from the fact that the design is labeled crossover.
A wash-out period is intended to separate treatment periods, but its presence alone does not demonstrate that carryover is absent. General statistical interpretation requires considering whether effects from a preceding condition may remain during the subsequent period. The registry record reports a 5-day wash-out and does not report evidence or an analysis regarding residual effects.
Why over-dispersion can matter
For outcomes analyzed using a count model, over-dispersion means the observed variability exceeds what a basic model assumes. If that excess variability is ignored, standard errors can be too small and confidence intervals too narrow, making estimates appear more precise than they are. This is a general statistical issue, not a reported feature of this trial. The primary outcome is a continuous scale measure, and the registry does not report an over-dispersion assessment or a count-model analysis.
Multiplicity and the set of outcomes
The primary outcome contains a total score and three subscale scores. The record also names two secondary scale outcomes. Examining multiple outcomes creates multiple opportunities to observe a result that appears notable by chance. A prespecified strategy can address this, for example by identifying one primary comparison or by adjusting inference across a family of tests. The registry record does not report a multiplicity adjustment or explain how confirmatory conclusions would be drawn across the scores.
The registry describes analysis of variance but does not report model diagnostics, assumptions, covariate adjustments, treatment-by-time contrasts, or a method for handling incomplete observations. Those choices can affect estimates and uncertainty. The absence of these details in the registry record does not show which methods were ultimately used; it means the posted record does not establish them.
Planning calculations and observed results
Sample-size illustrations are planning exercises, not evidence about the trial’s findings and not observed power. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described relative to an observed effect. No observed efficacy effect is reported in the registry record, and the record does not report its own sample-size justification. Consequently, planning scenarios cannot substitute for an estimate with uncertainty based on participants’ outcome data.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome covers PANSS total score and three subscale scores. The registry also lists two secondary outcomes: change in the Clinical Global Impression scale and change in the Calgary Depression Scale for Schizophrenia at 3 weeks. This set of outcomes raises a multiplicity question: when several outcomes are analyzed, the chance of at least one apparently notable result can increase. A statistical plan can define a primary comparison or specify an adjustment, but neither an adjustment nor a hierarchy of tests is reported in the registry record.
The record states that the efficacy analysis included participants who received all doses of each intervention and completed all study visits. This is a restricted analysis population based on treatment receipt and completion. The registry does not report how many participants met the criterion, how many were excluded, or whether any additional analysis population was used. It also does not report the amount or pattern of missing outcome data, reasons for missingness, or methods used to handle missing measurements.
These omissions matter particularly in a crossover trial, where usable data may depend on completion of both conditions and their assessments. If participants who complete the study differ from those who do not, estimates from completers may not represent all randomized participants. The record does not provide enough information to assess that possibility.
The registry’s brief analysis description does not specify whether multiplicity or missingness procedures were included in the final analysis. It is therefore not possible to determine how these issues affected the reported efficacy results; indeed, efficacy results are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| L-arginine | 0 | 13 | 0.0% |
| Placebo | 0 | 13 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| L-arginine | 0 of 13 |
| Placebo | 0 of 13 |
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 |
|---|---|
| L-arginine | 0 of 13 |
| Placebo | 0 of 13 |
The registry lists 13 participants at risk in each condition for serious adverse events, other adverse events, and deaths. It records 0 serious adverse events and 0 other adverse events for L-arginine, and the same counts for placebo. Deaths are recorded as 0 in each condition. These are the safety figures entered in the registry record.
Because this was a crossover study, the condition-specific groups may represent participants exposed to each condition rather than separate sets of people. The registry does not explain the counting rules for these entries or provide event-level detail. The figures should therefore be read as the recorded counts by condition, not as evidence that the treatments were compared in independent groups.
A recorded zero means that no events of that category are entered for the listed risk group in the posted record. It does not establish that every possible harm was assessed, that follow-up was complete, or that the study could exclude uncommon events. The registry lists no top serious adverse-event terms. It does not report further details about event ascertainment, duration of safety follow-up, or the handling of overlapping exposure periods.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, masked crossover study was conducted to examine L-arginine added to treatment as usual in schizophrenia. It specifies the planned treatment sequences, the wash-out period, and symptom scales intended to measure outcomes. It also records an enrollment of 13 participants and safety counts by condition.
It does not establish the comparative efficacy of L-arginine and placebo. The registry record does not report PANSS changes, secondary outcome values, treatment contrasts, confidence intervals, or statistical test results. There is therefore no basis in the posted results to describe the direction or magnitude of a symptom difference, or to judge its precision. A missing result is not a null result: it cannot be interpreted as showing that conditions were alike or that either condition had an effect.
The design also sets limits on what can be inferred from the available entries. Crossover studies rely on participants’ measurements under both conditions, and interpretation depends on completion, period and sequence effects, and possible carryover. The record does not report those analyses or participant completion details. Its stated efficacy population is limited to people who received all doses and completed all visits, but the number meeting that definition is not reported.
The zero adverse-event counts are descriptive registry entries for the listed categories and risk groups. They do not establish the absence of all harms, nor do they provide detailed information on how events were collected. Enrollment was small as recorded, and the registry does not report a trial-specific sample-size justification. These points limit what can be concluded about precision and safety from the posted record.
The appropriate reading is thus narrow: the registry records a completed trial and its intended outcomes, but does not provide the outcome results needed to answer the primary comparative question. No conclusion about whether L-arginine changed symptoms, or about the clinical importance of a possible difference, can be drawn from these entries.
13. Why This Trial Matters Statistically
This trial is statistically notable for combining a crossover design with repeated symptom measurements. In principle, having each participant receive both L-arginine and placebo permits comparisons within the same person, which can reduce the influence of stable differences between participants. That benefit depends on an analysis that recognizes the relationship between repeated observations and accounts for treatment order and time period.
The registry’s brief statistical description names an analysis of variance with treatment and pre- and post-treatment measurements, but it does not explain how the model addresses the crossover structure. This makes the distinction between a design label and an analysis plan especially important. The record is not detailed enough to establish how period, sequence, or carryover were treated, or whether the final analysis followed the described approach.
The endpoint also illustrates the need to distinguish an overall scale score from its component dimensions. The primary outcome includes PANSS total and positive, negative, and general psychopathology subscale scores. Those measures may describe related but non-identical aspects of symptoms. Considering multiple scores raises questions about multiplicity and how results should be prioritized; the registry does not report a strategy for these questions.
Finally, statistical interpretation requires results and uncertainty, not only a design description. Without posted means, changes, treatment contrasts, or confidence intervals, readers cannot assess the observed effect or its precision. The record therefore offers a useful example of how an apparently well-described study question can remain unanswered when outcome reporting and analysis detail are absent.
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 what the registry records about this trial. First, efficacy outcomes are not reported in the registry record. This prevents assessment of PANSS changes and the listed secondary scale outcomes, including their variability and uncertainty. It also means that the planned primary comparison cannot be reconstructed from the registry entries.
Second, the recorded enrollment was 13, while the study description anticipated 14. The record does not explain the difference, report the number randomized to each sequence, or give participant flow through the treatment periods. It is also unclear how many participants met the efficacy analysis criterion of receiving all doses and completing all visits.
Third, the registry provides only a brief analysis description. It does not report a detailed model for the crossover data, how treatment sequence or period was handled, whether carryover was assessed, or how incomplete measurements were addressed. These omissions prevent a full evaluation of the statistical assumptions and analysis choices.
Fourth, the primary outcome includes multiple PANSS scores, with additional secondary measures. A multiplicity strategy is not reported. The record also does not report a trial-specific sample-size justification, so the rationale for the anticipated enrollment cannot be evaluated.
Finally, the safety entries contain zero recorded events in the listed categories, but detail on ascertainment and follow-up is not reported. These limitations concern the available registry record and should not be mistaken for proof that the study did not collect further information outside it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: L-arginine in Treatment as Usual in Schizophrenia — NCT00718510.
- Registry record last updated 2017-09-05; status last verified 2017-09.
- Results first posted 2017-09-05.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a completed randomized, double-blind, quadruple-masked, placebo-controlled crossover trial of L-arginine added to treatment as usual in schizophrenia or schizoaffective disorder. Enrollment was 13, while the study description anticipated 14. Planned treatment consisted of 3 weeks per condition, separated by a 5-day wash-out.
The primary outcome was change in PANSS total and subscale scores at 3 weeks. Secondary outcomes were changes in the Clinical Global Impression scale and Calgary Depression Scale for Schizophrenia. The registry describes an analysis of variance but does not provide a detailed final analysis plan.
Numerical efficacy results, treatment contrasts, and estimates of precision are not reported in the registry record. The listed adverse-event and death counts are 0 for both conditions. The available record therefore describes the study design and planned measurements but does not answer the comparative efficacy question.