Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia (NCT02104752), a randomized phase 1, phase 2 study. The primary outcome is Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB).

2. Clinical Question

The trial asks whether curcumin nanoparticles, added for people with schizophrenia who were already receiving a stable dose of antipsychotic, affect cognitive test scores compared with matched placebo. Its primary measure is the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). The registry lists measurements at baseline, Week 4 and Week 8, so the intended assessment covers cognition over more than one post-baseline time point.

This is a question about a measured cognitive score, not a direct test of every aspect of schizophrenia or overall functioning. The registry also names secondary measures covering EEG mismatch negativity, BDNF, psychiatric rating and negative symptoms. The record does not provide results for those measures either. The clinical question can therefore be described from the trial plan, but the available registry information does not establish the direction, size or precision of any treatment-group difference.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group Phase 1/Phase 2 study. Randomization means assignment to the study arms was intended to occur by chance. Quadruple masking indicates that the record identifies the trial as masked at four levels, but it does not specify which people or roles those levels represent. The parallel-group model means the arms were compared as separate groups rather than in a crossover sequence.

The listed interventions are curcumin and placebo. The curcumin arm is described as receiving Theracurmin-formulated curcumin nanoparticles at 360 mg/day, divided into two oral doses each day. The placebo arm is described as receiving a matched sugar pill, 2 capsules twice daily. The trial summary places this treatment in the context of participants already receiving a stable antipsychotic dose; further details of background treatment are not reported in the registry record.

Enrollment is listed as 39. The sponsor is VA Greater Los Angeles Healthcare System. The recorded start is 2014-07, primary completion is 2016-05, and status is completed. These dates describe the registry milestones; they do not provide the timing or completeness of follow-up for every participant.

The primary endpoint is the MCCB, with measurements specified at baseline, Week 4 and Week 8. The registry lists four secondary outcomes: EEG mismatch negativity, BDNF, the Brief Psychiatric Rating Scale and the Clinical Assessment Interview for Negative Symptoms. It lists 5 outcome measures but 0 analyses. The record does not report the allocation ratio, concealment procedures, detailed masking roles, treatment adherence, participant flow or the statistical model used to compare groups. Those details should not be inferred from the design labels alone.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), measured over Baseline, Week 4, Week 8.

The primary endpoint is the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. It reports a mean score on a scale, with standard deviation as the stated measure of dispersion. Measurements are listed for baseline, Week 4 and Week 8.

The MCCB was developed through the National Institute of Mental Health-sponsored MATRICS initiative for assessing cognition in clinical trials of cognition-enhancing drugs. It combines 10 tests covering 7 cognitive domains: speed of processing, verbal memory, visual memory, working memory, reasoning and problem solving, attention/vigilance, and social cognition. The battery takes approximately 65 minutes to administer and produces age- and gender-corrected normed T-scores, including a global composite score and domain scores.

The described T-score range is 0 to 100, with a mean of 50; higher scores indicate better overall cognitive functioning. These properties help explain why the measure is used: it offers a structured assessment across several cognitive domains rather than relying on a single task. The registry record does not identify which specific MCCB score was selected for the primary comparison, nor does it report the group means, standard deviations or treatment contrast at any listed time point. The clinical meaning and precision of a difference therefore cannot be assessed from the registry results described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General explanation: this is a continuous-outcome setting because the MCCB is reported as a score, and the registry specifies a mean and standard deviation. A mean describes the central level of scores in a group. A standard deviation describes how spread out individual scores are around that group mean. These summaries are not interchangeable: a similar average can occur alongside different degrees of participant-to-participant variability.

To compare randomized groups, an analysis would ordinarily need to define the outcome being compared, the time point or time points, the analysis population and the statistical approach. The registry record identifies measurements at baseline, Week 4 and Week 8 but does not report a treatment contrast at any of them. It does not state whether the intended comparison was based on change from baseline, scores at follow-up adjusted for baseline, or another approach. Those alternatives can answer related but distinct statistical questions, and the record does not permit choosing among them.

General explanation: repeated measurements can provide information about both the level and course of an outcome. They also require a clear strategy for handling the correlation between measurements from the same participant. Treating repeated scores as unrelated observations would generally fail to reflect that dependence. A model can account for within-participant correlation, but the appropriate form depends on the design and data. The registry record does not report a repeated-measures model, covariance structure, or other method for handling the MCCB schedule. No particular model should be attributed to the investigators.

Precision matters alongside the estimated difference. A confidence interval gives an uncertainty range around an estimate under the chosen analysis and assumptions. A narrow interval indicates greater precision than a wide one, while neither width nor statistical significance alone establishes clinical importance. The registry record does not report a confidence interval, standard error or primary comparison estimate. It also does not provide a threshold for interpreting a meaningful MCCB difference. Consequently, the posted information cannot support a judgment about either precision or clinical relevance.

General explanation: p-values are often used to assess how compatible observed data are with a specified null hypothesis, assuming the statistical model is appropriate. A p-value is not the probability that the null hypothesis is true, and it does not quantify the size of an effect. No primary-outcome p-value is reported in the registry record. The absence of a reported result is not evidence that a test was nonsignificant; it means the registry entry does not provide that analysis.

The record identifies several outcomes and multiple MCCB measurement times. When many outcomes, time points or comparisons are examined, the chance of at least one apparently unusual result can increase. General statistical practice may address this through prespecified primary comparisons, multiplicity adjustments, or a careful distinction between confirmatory and exploratory analyses. The registry record does not report which strategy, if any, was used. The listed secondary outcomes do not by themselves reveal whether the analysis plan controlled multiplicity.

Planning calculations should also be distinguished from results. The stated planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation and an effect defined as a stated fraction of the observed effect. Such calculations concern participants per arm for a future study under assumptions. They do not describe the trial’s observed statistical power, and they do not show that the study achieved a particular level of power. The specific numerical planning results and the effect estimate on which they depend are not reported in the registry record.

Finally, an analysis requires decisions about missing outcome measurements and the participants included. General methods can range from analyses of available observations to approaches that model or impute missing data, with different assumptions. An analysis population might include all randomized participants or a defined subset, but the correct interpretation depends on the prespecified plan and actual participant flow. The registry record does not report missing-data methods, analysis populations, exclusions or the treatment of protocol deviations. These omissions prevent assessing the robustness of any primary comparison even if a result were otherwise available.

10. Multiplicity, Missing Data and Analysis Populations

The MCCB schedule includes baseline, Week 4 and Week 8, and the registry also lists four secondary outcomes: EEG mismatch negativity, BDNF, the Brief Psychiatric Rating Scale and the Clinical Assessment Interview for Negative Symptoms. Considering multiple endpoints or time points raises a multiplicity question: the more comparisons examined, the more opportunities there may be for an apparently notable result arising by chance. General approaches include prespecifying a primary contrast, adjusting inference across a family of comparisons, or treating some analyses as exploratory. The registry record does not report which approach was used or whether any adjustment was made.

The primary endpoint is not reduced in the record to one comparison across its listed time points. The record lists 0 analyses. It does not report a hierarchy of endpoints, a prespecified analysis plan, subgroup analyses or interim analyses. Whether these were absent or simply not documented is not reported in the registry record.

Missing-data handling is also not reported in the registry record. There is no account of the number of participants with MCCB measurements at each time point, reasons for missing measurements, imputation, or sensitivity analyses. Without those details, readers cannot assess whether the available outcome data might differ systematically from the data that would have been collected with complete follow-up.

The analysis population is not reported in the registry record. It does not specify which randomized participants were included in any outcome analysis, or how treatment discontinuation, adherence or protocol deviations were handled. These details matter because an analysis of all randomized participants and an analysis restricted to participants with particular follow-up or adherence characteristics can have different interpretations. The registry information does not establish which, if any, was used.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry’s adverse-event record lists 17 participants at risk in the Curcumin group and 19 at risk in the Sugar Pill group. It reports 0 participants affected by serious adverse events in each group and 0 affected by other adverse events in each group. These are the counts recorded for the adverse-event categories in the registry entry; they are not a detailed account of individual events or event rates over a specified follow-up period.

Death counts are not reported in the registry record. The record does not give the adverse-event observation period, definitions, severity grading, causality assessment, ascertainment procedures, or information about completeness of follow-up. It therefore does not establish whether every participant was observed for the same duration or whether all events of interest were captured.

Zero recorded events should not be interpreted as proof that no harm occurred, nor as a complete safety assessment. The event counts do not describe the nature or likelihood of uncommon events, and they cannot be used to compare risk precisely without further information. They should be read narrowly as the adverse-event counts posted in the registry record.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a randomized, quadruple-masked, parallel-group trial compared curcumin with matched placebo and listed the MCCB as its primary outcome. It describes the curcumin formulation and dose, the placebo schedule, measurement times and several secondary outcomes. It also records enrollment of 39 and a completed status. These details describe the study, not its treatment effect.

The record does not report MCCB group results or a comparison across baseline, Week 4 and Week 8. There is no reported estimate of the difference, confidence interval or p-value. As a result, the posted information does not show whether the groups’ cognitive scores differed, in which direction any difference went, or how precisely a difference was estimated. It also does not establish that scores changed within either group.

The endpoint has a clear measurement rationale: the MCCB is a structured battery spanning several cognitive domains, with higher T-scores indicating better overall cognitive functioning. That design feature does not guarantee that a given score difference is clinically important. The registry record does not provide an interpretation threshold or the data required to assess one.

The serious and other adverse-event counts are recorded as zero for both groups in the registry listing, while death counts are not reported. Those entries are not sufficient to establish that the intervention is safe or that risks are equivalent between groups. Follow-up and event-ascertainment details are not reported in the registry record.

Accordingly, the result that can be stated is limited: the registry describes a completed trial and its planned cognitive outcome, but does not report an analyzable primary comparison. This is not evidence of benefit, evidence of no benefit, or a basis for medical decisions. It is a limitation of what the registry record makes available for statistical interpretation.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison using a multidomain cognitive measure rather than a single test. The MCCB was developed for cognition-focused trials and combines tests across speed of processing, memory, working memory, reasoning and problem solving, attention/vigilance, and social cognition. Its global composite and domain scores can represent different aspects of performance, making clear specification of the primary score and comparison especially important.

The study schedule lists baseline, Week 4 and Week 8. Multiple measurements can help describe change over time, but they also make the choice of estimand and analysis consequential. The registry record does not report how repeated measurements were modeled or which time-point contrast was primary. It also lists multiple secondary outcomes, while the multiplicity strategy is not reported. These are central issues for interpreting a trial with several outcomes and times of assessment.

The entry illustrates why registration details and outcome reporting serve different purposes. Design labels, interventions and endpoints establish what was planned or recorded, but they cannot replace group outcome summaries and an analysis of uncertainty. Here, the registry lists 0 analyses and does not report a primary treatment-effect estimate. The study therefore cannot answer its statistical question through the available result information.

For researchers, the distinction is practical: transparent reporting should connect the prespecified outcome and time point to the analysis population, method, estimate and uncertainty. Without that chain, readers cannot distinguish an imprecise estimate from a null result or an unreported analysis. The record supports examination of the measurement plan and documentation gaps, but not a conclusion about the cognitive effect of curcumin.

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 principal limitation for interpretation is that the registry record does not report a primary-outcome comparison. Although it names the MCCB and gives the assessment schedule, it does not provide group means, standard deviations, effect estimates, confidence intervals or p-values. The listed analysis count is 0. Therefore, the trial’s cognitive results and their precision cannot be evaluated from the record.

The endpoint is specified at several time points, but the record does not identify a single comparison or explain how baseline measurements were incorporated. It does not state which MCCB score was selected for primary inference, despite the description of a global composite and domain scores. Multiplicity handling is not reported despite the multiple time points and secondary outcomes.

Participant flow and analysis details are also unavailable in the registry record. It does not report outcome completion at each time, missing-data methods, analysis populations, adherence, discontinuations or protocol deviations. These omissions limit assessment of the representativeness and reliability of any outcome analysis. The registry’s enrollment figure alone does not indicate how many participants contributed data to each outcome.

Safety interpretation is constrained by sparse reporting: adverse-event counts are listed, but observation periods, definitions and ascertainment details are not. Death counts are not reported in the registry record. Finally, the available information does not establish the treatment allocation ratio, the roles included in quadruple masking, or the statistical plan. These limitations concern what can be learned from the registry entry and should not be treated as proof that particular procedures or analyses did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia — NCT02104752.
• Registry record last updated 2019-05-15; status last verified 2019-04.
• Results first posted 2019-05-15.
• 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.

18. Record Summary

The registry record describes NCT02104752, a completed randomized, quadruple-masked, parallel-group Phase 1/Phase 2 trial sponsored by VA Greater Los Angeles Healthcare System. Enrollment is listed as 39; the recorded start is 2014-07 and primary completion is 2016-05. The trial compared Theracurmin-formulated curcumin nanoparticles, given at 360 mg/day in twice-daily oral doses, with matched placebo described as 2 capsules twice daily.

The primary outcome is the MCCB mean score, measured at baseline, Week 4 and Week 8. The record lists four secondary outcomes, 5 outcome measures and 0 analyses. It does not report a primary-outcome comparison, statistical plan, missing-data approach or analysis population. The adverse-event entry reports zero serious and zero other adverse events in each listed group; death counts are not reported in the registry record. The available information describes the design and selected recorded counts, but does not establish the cognitive effect or provide a complete assessment of safety.