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 The Effect of N-Acetyl Cysteine on Cortical Erosion in Early Stage Schizophrenia (NCT01339858), a randomized phase 4 study. The primary outcome is Cortical Thickness.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01339858 |
| Phase | Phase 4 |
| Condition | Schizophrenia, Psychotic Disorder NOS, Schizoaffective Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Indiana University |
| Results posted | Yes |
2. Clinical Question
Population
People described in the registry summary as having early-stage psychosis. The listed conditions are schizophrenia, psychotic disorder NOS, schizoaffective disorder, and schizophreniform disorder. Further eligibility details are not reported in the registry record.
Intervention
N-acetyl cysteine (NAC) added to existing antipsychotic treatment. The record describes unmarked capsules, with NAC capsules containing 600 mg and dosing beginning at 600 mg/d, titrated over 5 weeks to a maximum of 3600 mg/d. Actual treatment received is not reported in the registry record.
Comparator
A matched sugar-pill placebo. The study summary frames the comparison as NAC add-on treatment versus placebo in the context of existing antipsychotic treatment.
Primary question
After 12 months, does the NAC add-on group have less cortical erosion, assessed in part through cortical thickness, than the placebo group? A numerical estimate for this comparison is not reported in the registry record.
The study also describes questions about working memory and semantic memory, magnetic resonance spectroscopy measures, electrophysiological attention measures, symptoms, functional measures, and cognitive functioning. These are additional aims, not substitutes for the primary cortical-thickness question. The registry summary describes cortical volume and cortical white matter density assessed by DTI as part of the hypothesis about cortical erosion. The posted primary outcome is titled Cortical Thickness, with millimeters as its unit and a 12-month timeframe.
The clinical question is therefore specific to an add-on treatment comparison and a structural brain measure. It is not a comparison of NAC with antipsychotic treatment, and it does not by itself address every outcome listed in the study summary. The registry record does not report the numerical primary comparison or enough detail to determine how the multiple primary-outcome categories and time points were combined in the analysis.
3. Trial Design
The registry describes a phase 4, randomized, double-masked, parallel-group study with an enrollment of 60. Its status is completed. The recorded study start is 2011-05, and the primary completion date is 2015-12. The sponsor is Indiana University. These registry entries describe the study record; they do not establish how many participants were ultimately included in each outcome analysis.
Participants were assigned to an NAC arm or a sugar-pill arm. The intervention description says NAC was provided in unmarked capsules and the placebo was matched. The study summary frames NAC as an addition to existing antipsychotic treatment. Details of sequence generation, allocation concealment, how masking was maintained, treatment adherence, and any changes to treatment are not reported in the registry record. The parallel model means the record describes groups receiving their assigned study treatment alongside one another, rather than a crossover comparison.
The stated treatment period for the primary question is 12 months. The registry describes cortical thickness as the primary outcome and also refers to cortical volume and cortical white matter density in the primary hypothesis. The primary outcome record identifies a least-squares mean and standard error, but the numerical result is not reported in the registry record. It also indicates multiple categories or time points, so the primary outcome is not reduced to one comparison in the posted results summarized by these registry entries.
Secondary outcomes include working memory, glutamine/glutamate level changes, attention measures, symptoms of a psychotic disorder, cognitive functioning, functional status, and mismatch negativity voltage differences. The record gives no detailed account of the randomization procedure, the intended analysis population, participant flow, or the handling of protocol deviations. Enrollment is a study-level registry figure and should not be read as the number analyzed for every outcome.
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 | N-Acetyl Cysteine | Sugar Pill |
|---|---|---|
| STARTED | 30 | 30 |
| COMPLETED | 14 | 18 |
| NOT COMPLETED | 16 | 12 |
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 | N-Acetyl Cysteine | Sugar Pill | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 30 | 60 | |
| Age, Categorical: <=18 years | Participants | 2 | 1 | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 28 | 29 | 57 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 22.2 (SD 4.2) | 25.0 (SD 5.2) | 23.1 (SD 4.8) |
| Sex: Female, Male: Female | Participants | 7 | 6 | 13 |
| Sex: Female, Male: Male | Participants | 23 | 24 | 47 |
| Region of Enrollment: United States | participants | 30 | 30 | 60 |
6. Primary Endpoint
The registry lists the primary outcome as Cortical Thickness, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | mm |
| Endpoint classification | Continuous Endpoint |
Cortical thickness is a structural brain measurement expressed in millimeters. In this study, it was selected as an indicator related to the stated hypothesis of less cortical erosion after 12 months of add-on NAC compared with placebo. The registry identifies the outcome as a least-squares mean, with standard error as its dispersion measure. A least-squares mean is a model-based group mean; its exact interpretation depends on the statistical model and any adjustment variables, which are not reported in the registry record.
As a general statistical point, a continuous measure such as thickness can retain information about the degree of measurement rather than reducing observations to a yes-or-no event. A mean can describe a group’s average measurement, while the uncertainty around that estimate helps readers judge how precisely it is known. The standard error describes the precision of an estimated mean under the model; it is not the spread of individual measurements. The registry record does not report the group estimates, their standard errors, a between-group contrast, or a confidence interval, so the size and precision of the primary comparison cannot be assessed from these registry entries.
The study summary also mentions cortical volume and cortical white matter density assessed by DTI in its primary hypothesis. The recorded primary outcome is specifically titled Cortical Thickness. The record notes multiple categories or time points and does not reduce them to one comparison, which makes it important not to treat the endpoint title alone as a complete account of the analysis. Details about image acquisition, measurement reliability, the selected brain regions, and the exact endpoint calculation are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question, design, and intended measurement, but it does not provide a numerical primary outcome result. There is no posted group mean, standard error, treatment contrast, confidence interval, or p-value for cortical thickness in the registry record for this analysis. Accordingly, the magnitude, direction, and precision of the primary comparison cannot be described. The study’s stated hypothesis is not itself evidence that the hypothesized difference was observed.
The primary outcome is described as a least-squares mean at 12 months, but the analysis model and its covariates are not reported in the registry record. A least-squares mean can account for model terms, so it need not be identical to a simple arithmetic average. Without the model specification and numerical estimates, readers cannot determine what adjustment was made or how much the estimate depends on modeling choices. The record also states that the primary outcome has several categories or time points and is not reduced to one comparison. That limits interpretation of the primary question as a single test.
There are secondary outcomes spanning cognition, symptoms, functioning, spectroscopy, and electrophysiology. The record lists 10 outcome measures, but detailed numerical findings for them are not reported in the registry record. The list of outcomes does not establish that every planned measure was collected or analyzed, nor does it show which results were prespecified as confirmatory. The analysis plan and any approach to multiple comparisons are not reported in the registry record.
Safety information is presented separately from the primary structural outcome. The adverse-event record lists serious adverse events affecting 3 participants in the NAC group and 2 in the sugar-pill group, with 30 at risk in each group. Other adverse events are listed for 28 and 27 participants, respectively, with 30 at risk in each group. Those counts are descriptive. They do not quantify the primary brain-imaging outcome, and the registry entries do not provide the event definitions, observation time, severity breakdown beyond the serious-event designation, or statistical comparison needed for a fuller safety analysis. Death counts are not reported in the registry record.
In general, statistical interpretation requires both an estimated effect and an assessment of uncertainty. A small p-value, if reported, would address compatibility with a null model under specified assumptions, not the clinical importance of an effect. A confidence interval would convey a range of values compatible with the data and model. Neither a p-value nor an interval for the primary comparison is reported in the registry record. No conclusion about benefit, lack of benefit, equivalence, or clinical relevance can be drawn from the study hypothesis or the design details alone.
9. Statistical Methods Explained
The registry identifies a randomized, double-masked, parallel design. As a general statistical principle, random assignment is intended to make treatment groups comparable on average at the point of assignment, including for characteristics that are not measured. It does not guarantee identical groups, particularly in a study with limited enrollment. Masking is intended to reduce the influence of treatment knowledge on behavior, outcome assessment, or other decisions. The registry does not report how the random sequence was generated, how assignment was concealed, who remained masked, or whether masking was successful. The design labels alone do not answer those operational questions.
What does a least-squares mean represent?
The primary outcome is reported as a least-squares mean. In general, this is a mean estimated from a statistical model, often at specified values or distributions of other model variables. The result can differ from a raw group average when the model adjusts for covariates or accounts for repeated observations. The meaning of the reported estimate therefore depends on the model specification, including its terms, assumptions, and treatment of repeated measurements. Those details are not reported in the registry record. The record also does not provide numerical group means or a contrast between groups, so the estimated treatment difference cannot be interpreted.
The dispersion measure is identified as standard error. In general, standard error describes the sampling precision of an estimated quantity under a model. It is distinct from a standard deviation, which describes variation among individual observations. A confidence interval is commonly constructed using an estimate and its standard error, along with a method and confidence level. No confidence interval or standard error value for the primary comparison is reported in the registry record. Standard error alone would not describe the full range of individual cortical-thickness measurements.
How should the endpoint and time point be understood?
The stated primary timeframe is 12 months, and cortical thickness is measured in millimeters. A treatment contrast at a specified follow-up time is not necessarily the same as a contrast in change from baseline. The registry entries do not clarify whether the primary analysis compares follow-up values, changes from baseline, or a model using measurements across time. Baseline measurement procedures, visit windows, and the handling of measurements taken outside the intended timeframe are not reported in the registry record. The primary outcome note indicates several categories or time points, but the record does not reduce them to a single comparison.
The summary identifies additional structural measures: cortical volume and cortical white matter density assessed by DTI. It also describes secondary assessments involving functional MRI tasks, magnetic resonance spectroscopy, electrophysiology, symptoms, functioning, and cognition. These measures may use different scales and statistical methods. The registry record does not specify the models used for each measure, whether outcomes were analyzed as continuous or categorical variables, or how repeated assessments were handled.
What do the planning assumptions mean?
The sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration varies the effect to detect as a stated fraction of the observed effect. In general, such calculations ask how many participants per arm a future design might require under chosen assumptions. They are not observed power for this completed trial and are not evidence that the study had a particular probability of detecting an effect. The registry does not report a sample-size justification from the trial’s own design, and the numerical planning illustrations are not included in the registry record.
Planning calculations depend on assumptions about the effect size, variability, allocation, significance threshold, and analysis. If the assumed effect comes from an observed estimate, uncertainty in that estimate matters; a planning scenario should not be mistaken for an independent confirmation. The record does not state whether the trial’s original design used these assumptions or whether any revisions were made. Any interim analyses, stopping rules, or formal monitoring plan are not reported in the registry record.
What can the adverse-event counts establish statistically?
The serious and other adverse-event figures are counts in groups, with the numbers at risk also recorded. Such counts are descriptive summaries. A comparative interpretation would depend on the event definitions, participant follow-up, whether people could contribute more than one event, and the prespecified method of analysis. Those details are not reported in the registry record. The listed serious-event terms and percentages are not linked to a particular treatment arm in the registry record, so they should not be used to infer arm-specific event rates. No statistical test or interval for the adverse-event comparison is reported.
Overall, the design and endpoint labels identify the intended framework, while the missing numerical estimates and analysis specifications prevent reconstruction of the primary inference. General statistical concepts can clarify what the methods would mean, but they cannot fill in the absent model, results, or analysis decisions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures and several secondary outcome areas, including working memory, glutamine/glutamate level changes, attention, symptoms, cognition, functional status, and mismatch negativity. The study summary describes still more specific assessment types. Testing multiple outcomes or time points raises a multiplicity question: when many statistical comparisons are made, the chance of at least one apparently unusual result can increase. As a general principle, a prespecified hierarchy or adjustment method can help define how multiple findings should be interpreted. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which comparisons were designated confirmatory.
The primary outcome record says it has several categories or time points and is not reduced to one comparison. The registry does not explain how these categories or time points were selected, combined, or prioritized. The number of analyses listed in the record does not establish that there was only one analysis across all outcomes, nor does it reveal the full analysis plan. No outcome-specific estimates or p-values are included in the registry record.
Missing-data handling is not reported in the registry record. In general, this matters when participants lack a follow-up measurement, because the analysis may depend on assumptions about why data are missing and how missing values are handled. The record does not specify the amount or pattern of missing outcome data, any imputation method, or sensitivity analyses. The analysis population is also not reported: it is unclear from these registry entries whether analyses were planned by randomized assignment, treatment received, or another definition. Participant flow and exclusions from individual outcome analyses are not given. These omissions limit assessment of both bias risk and the population to which any result might apply.
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 |
|---|---|---|---|
| N-Acetyl Cysteine | 3 | 30 | 10.0% |
| Sugar Pill | 2 | 30 | 6.7% |
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 |
|---|---|
| N-Acetyl Cysteine | 28 of 30 |
| Sugar Pill | 27 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | N-Acetyl Cysteine | Sugar Pill |
|---|---|---|---|
| Psychosis Exacerbation | Psychiatric disorders | 2 of 30 | 2 of 30 |
| Asthma Exacerbation | Respiratory, thoracic and mediastinal disorders | 1 of 30 | 0 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | N-Acetyl Cysteine | Sugar Pill |
|---|---|---|---|
| Weight Gain | Metabolism and nutrition disorders | 3 of 30 | 6 of 30 |
| Depressed Mood | Psychiatric disorders | 4 of 30 | 4 of 30 |
| Nausea and Vomiting | Gastrointestinal disorders | 3 of 30 | 5 of 30 |
| Headache | Nervous system disorders | 3 of 30 | 2 of 30 |
| Sedation | General disorders | 2 of 30 | 3 of 30 |
| Insomnia | General disorders | 3 of 30 | 2 of 30 |
| Dizziness | Nervous system disorders | 2 of 30 | 3 of 30 |
| Upper Respiratory Infection | Infections and infestations | 2 of 30 | 3 of 30 |
| Illness Exacerbation | Psychiatric disorders | 3 of 30 | 0 of 30 |
| Nasal Congestion | General disorders | 1 of 30 | 2 of 30 |
Serious events with the highest arm-level rate: psychosis exacerbation (6.7%), asthma exacerbation (3.3%).
The adverse-event record gives group-level counts for serious and other adverse events. In the NAC group, 3 participants are listed as having serious adverse events, with 30 at risk; in the sugar-pill group, 2 are listed, with 30 at risk. Other adverse events are listed for 28 participants in the NAC group and 27 in the sugar-pill group, with 30 at risk in each group. These are the registry counts and should be read as descriptive records, not as a test of whether the groups differ.
The registry also lists Psychosis Exacerbation at 6.7% and Asthma Exacerbation at 3.3% among the top serious-event terms. The registry entries do not identify the treatment group for these terms or provide further event-level detail. The percentages should not be assigned to either arm based on the group counts. The record does not specify whether people could have more than one event, how long each participant was observed for safety, or how the events were defined and adjudicated.
Deaths are not reported in the registry record. No comparative statistical estimate or uncertainty interval for adverse events is reported. In general, adverse-event counts need context about duration of exposure, ascertainment, and event seriousness; counts alone do not establish causation. These registry figures describe reported events and do not, by themselves, provide a complete safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record identifies a clinical question and a study design: randomized assignment, double masking, and a parallel comparison of NAC with a matched sugar-pill placebo in an early-stage psychosis study. It also identifies cortical thickness at 12 months as the primary outcome. Those features describe what the trial was intended to investigate, not what its primary analysis found.
The numerical result for cortical thickness is not reported in the registry record. Without a group estimate and a between-group comparison, it is not possible to say whether the observed result favored either group, how large any difference was, or how precisely it was estimated. The registry summary’s stated hypothesis cannot be treated as a result. Nor does the absence of a numerical result establish that there was no difference. A missing estimate is not equivalent to evidence of equivalence or evidence that an effect is absent.
In general, a treatment effect estimate and its uncertainty answer different questions. The estimate describes the direction and magnitude of the observed contrast; an uncertainty interval indicates how imprecisely that contrast is known under the analysis assumptions. Statistical significance, if available, would not by itself establish clinical importance. The record does not report the relevant primary estimates, intervals, or test results, so those distinctions cannot be applied to this comparison.
The safety counts offer limited descriptive information, but they do not answer the cortical-thickness question. The listed serious-event terms are not assigned to treatment groups in the record, and key details about event timing and analysis are not reported. The secondary outcomes are named, but their numerical results are not reported in the registry record either. Consequently, the available information cannot support a broad conclusion about all measured domains.
The most defensible reading is that the registry documents a completed trial with a defined add-on treatment question and a stated structural brain endpoint, while the primary numerical findings and essential analysis details are not reported in the registry record. Interpretation should remain limited to those design and reporting details.
13. Why This Trial Matters Statistically
This trial is statistically notable because it connects a randomized treatment comparison with a continuous structural brain measure. A continuous endpoint such as cortical thickness can capture variation in measurement rather than collapsing observations into a binary event. At the same time, interpretation depends on how the measure was obtained, modeled, and compared across groups. The registry names a least-squares mean and standard error but does not report the model specification or numerical estimates, underscoring why an endpoint label alone is not enough to evaluate evidence.
The study also illustrates the distinction between a focused primary question and a broad set of additional outcomes. The record lists cognitive, functional, symptomatic, imaging, and electrophysiological measures. Such breadth can describe several dimensions of a research question, but it also makes prespecification and multiplicity important. Without a reported hierarchy or adjustment approach, readers cannot know how the investigators intended to distinguish primary evidence from exploratory findings.
The safety record shows why counts need context. Group counts and numbers at risk are useful descriptive elements, yet they do not reveal exposure time, repeated events, or uncertainty around a comparison. The serious-event terms have no treatment-group attribution in the record, limiting their interpretation further.
Finally, the posted information separates the fact that a trial was completed from the availability of interpretable results. A completed status does not supply a treatment estimate, and the study hypothesis does not substitute for one. For biostatisticians and clinical researchers, this record is a reminder to assess design, endpoint definition, analysis transparency, and result reporting together. Here, the design and measurement intent are described, while the primary quantitative finding and important analytic details are not reported in the registry record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most immediate limitation for interpreting this trial is the lack of numerical primary-outcome results in the registry record. The record identifies cortical thickness, millimeters, a 12-month timeframe, a least-squares mean, and standard error, but it does not provide the group estimates, treatment contrast, uncertainty interval, or test result. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.
The primary-outcome note indicates several categories or time points and is not reduced to one comparison. The record does not clarify how these categories or time points relate to the primary hypothesis or how they were handled analytically. Although the summary also refers to cortical volume and cortical white matter density assessed by DTI, the registry entries do not explain how those measures fit into the primary outcome analysis.
Further limitations include the absence of detailed eligibility criteria, participant flow, baseline characteristics, outcome-specific analysis populations, and missing-data procedures. The randomization method, allocation concealment, masking details, adherence, model specification, and analysis plan are not reported in the registry record. These omissions prevent assessment of important design and analysis choices. The record’s enrollment figure should not be taken as the analyzed sample size for each outcome.
The secondary outcomes are listed without numerical findings in the registry record, and the approach to multiple comparisons is not reported. Safety information lacks detail on follow-up duration, event definitions, repeat events, and treatment-group assignment for the listed serious-event terms. Death counts are not reported in the registry record. These limitations constrain both efficacy and safety interpretation; they do not establish that the trial’s underlying analyses lacked such information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect of N-Acetyl Cysteine on Cortical Erosion in Early Stage Schizophrenia — NCT01339858.
- Registry record last updated 2019-05-08; status last verified 2019-04.
- Results first posted 2019-05-08.
- 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 NCT01339858, titled “The Effect of N-Acetyl Cysteine on Cortical Erosion in Early Stage Schizophrenia.” It is recorded as a phase 4, randomized, double-masked, parallel-group study sponsored by Indiana University, with enrollment of 60 and completed status. The recorded start is 2011-05, and primary completion is 2015-12.
The comparison is NAC added to existing antipsychotic treatment versus matched placebo. The primary outcome is cortical thickness in millimeters at 12 months, reported in the registry as a least-squares mean with standard error. The summary also discusses cortical volume and cortical white matter density, along with secondary cognitive, functional, symptomatic, imaging, and electrophysiological outcomes.
The numerical primary comparison, detailed analysis plan, missing-data approach, and analysis populations are not reported in the registry record. Safety counts are listed by group, while the listed serious-event terms are not assigned to a treatment group in the registry record.