Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity (NCT02118610), a randomized na study. The primary outcome is Positive and Negative Symptom Improvement.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group trial registered as NCT02118610. Its listed condition was schizophrenia, and its interventions were L-tetrahydropalmatine (l-THP) and a sugar pill. The registry describes the l-THP arm as receiving 30 mg BID. It gives no corresponding administration details for the sugar-pill arm. The phase is recorded as NA.

The enrollment was 63. That is the overall enrollment figure in the record; it should not be treated as the number analyzed for a particular outcome. The adverse-event record separately lists 29 people at risk in the l-THP group and 32 in the sugar-pill group. The registry does not report how participants were assigned to the outcome analyses, whether all enrolled participants received treatment, or whether anyone withdrew or was excluded.

The registry lists the sponsor as the University of Maryland, Baltimore. The recorded start is 2014-09, primary completion is 2018-12, and status is completed. These administrative details describe the trial record, but do not establish when individual participants were assessed or how long each person was followed.

The stated primary outcome concerns positive and negative symptom improvement at baseline and 4 weeks (endpoint). Improvement in cognitive function is listed as a secondary outcome. The registry record does not report the randomization procedure, allocation concealment, masking roles, treatment adherence, or details of the statistical analysis plan. It also does not report a primary outcome estimate, standard error, confidence interval, or hypothesis-test result. Consequently, the design can be described, but the comparative symptom results cannot be reconstructed from the posted results.

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

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 Positive and Negative Symptom Improvement, measured over Baseline and 4 weeks (endpoint).

The primary outcome is titled Positive and Negative Symptom Improvement. The registry describes measurement with the BPRS positive symptom subfactor, SANS, and BNSS at baseline and 4 weeks (endpoint). These instruments address psychiatric symptoms, with the BPRS description specifically identifying a positive-symptom subfactor and the other named scales addressing negative symptoms.

The registry also gives a scoring description for the total BPRS. It says that the total is calculated by adding scores for scales #1-#18, each ranging from 1=Not Present to 7=Very Severe; total scores range from 18 to 126, with higher scores indicating more severe psychiatric symptom ratings. That explanation applies to the described BPRS total score. It does not establish that the primary outcome used the total score rather than the stated positive symptom subfactor, nor does it define a combined endpoint across BPRS, SANS, and BNSS.

Repeated assessment from baseline to endpoint can describe symptom status over the stated interval, while comparisons between randomized groups can estimate differences associated with assigned treatment. The record does not state which scale or scales determined the primary analysis, how change was calculated, or how multiple scales were handled. Outcome values and a between-group estimate are not reported in the registry record, so the direction, magnitude, and precision of any difference are unavailable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. When implemented as intended, it can reduce systematic differences in measured and unmeasured characteristics at the point of assignment. That supports a causal interpretation of a between-group comparison, but does not guarantee that the groups remain comparable after withdrawals, nonadherence, or missing outcome measurements. The registry labels this trial randomized, but does not report the sequence-generation method, allocation concealment, or how participants were handled after assignment.

What does masking mean?

The record labels the trial quadruple-masked. Masking is intended to limit the influence of knowing treatment assignment on care, participant reporting, or outcome assessment. The registry does not identify which roles were masked or describe how masking was maintained. The sugar pill is listed as the comparator, but the record does not explain its appearance or administration. Thus the masking label is informative about the recorded design, but its implementation cannot be evaluated from this information.

How should a continuous symptom score be compared?

The primary outcome is described as a mean of a continuous measure with standard deviation as the dispersion measure. In general, a mean summarizes the average score in a group, while a standard deviation describes the spread of individual scores around that mean. A treatment comparison could concern endpoint scores, change from baseline, or an adjusted estimate; these approaches answer related but not identical questions. The registry record does not state which approach was used, and it reports no means, standard deviations, adjusted estimate, or between-group contrast. A numerical treatment effect therefore cannot be interpreted.

The record’s BPRS explanation says that higher total scores indicate more severe psychiatric symptom ratings. However, the primary description specifies the BPRS positive symptom subfactor as well as SANS and BNSS. The record does not state that all these measures share the same score range or direction, and it does not define a combined score. Interpretation should therefore remain tied to each named instrument rather than assuming one common scale.

What would uncertainty measures show?

In general, a standard error quantifies the sampling variability of an estimate under a statistical model. A confidence interval uses that uncertainty to describe a set of effect values compatible with the observed data and specified assumptions. It helps assess precision and whether effects of different sizes remain plausible. No standard errors or confidence intervals for the symptom outcomes are reported in the registry record. The direction and precision of an effect cannot be inferred from the design alone.

A hypothesis test assesses how unusual the observed data would be under a specified null model. Its p-value is not the probability that a treatment is effective, and it does not convey the effect’s clinical importance. Because no primary-outcome p-value or estimate is reported, neither statistical significance nor the evidence against a null comparison can be assessed from the posted results.

Why do distributional assumptions matter?

General statistical explanation: analyses of continuous scores often rely on assumptions about the outcome distribution and the behavior of residuals, the differences between observed and model-predicted values. If scores are strongly skewed, bounded, or concentrated at certain values, a simple normal-model analysis may represent the data poorly. The registry identifies a mean and standard deviation, but does not report score distributions, residual checks, transformations, or the model used. It is therefore not possible to assess whether the analysis assumptions were reasonable.

Over-dispersion is a general concern when observed variability exceeds what an assumed model allows. Underestimating variability can make uncertainty intervals too narrow and tests too optimistic. This is a general statistical issue, not a reported feature of this trial: the registry does not provide the outcome distributions or model diagnostics needed to assess it.

What can be learned from the planning illustration?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that an effect was detected. The primary comparison is not reduced to one result because the outcome has several categories or time points. No specific planning counts or observed primary effect are reported in the registry record, so no numerical sample-size implication can be interpreted from these registry entries.

In general, planning calculations depend on assumptions about the effect of interest, outcome variability, allocation, and analysis. If those assumptions differ from the trial’s actual design or results, the calculation does not describe the achieved precision. The record explicitly distinguishes its illustration from the trial’s own design. Its contents cannot substitute for the missing primary outcome estimates or analysis details.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description names the BPRS positive symptom subfactor, SANS, and BNSS, and specifies baseline and 4 weeks (endpoint). The record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report which measure, contrast, or time point was designated as the principal test, or whether the scales were analyzed separately or combined.

When multiple outcomes or comparisons are examined, the chance of obtaining at least one apparently unusual result can increase. General methods for addressing multiplicity include prioritizing a primary comparison in advance, adjusting significance thresholds, or interpreting a set of findings jointly. The registry record does not report whether any such approach was planned or used. It also does not report an analysis plan or interim analyses. No inference about the handling of multiplicity can therefore be made.

Missing-data methods are also not reported in the registry record. There is no account of missing endpoint assessments, withdrawals, reasons for missingness, imputation, or sensitivity analyses. Without this information, it is not possible to assess whether the analyzed participants represented everyone randomized or whether missing outcomes could have affected the comparison.

The record does not report analysis populations, such as an intention-to-treat population or a per-protocol population, and does not explain how participants were classified for analysis. Enrollment is recorded as 63, while the adverse-event entries list group-specific numbers at risk. Those safety denominators do not establish the symptom-outcome denominators. The absent analysis-population and missing-data details limit reproducibility and interpretation of any treatment estimate, even if one were available.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: severe neutropenia (3.1%).

The adverse-event record lists serious adverse events in 0 of 29 people at risk in the l-THP group and 1 of 32 in the sugar-pill group. Deaths are listed as 0 in each group. These are descriptive counts in the registry record; they do not establish that treatment caused or prevented an event.

The record also lists a serious adverse-event term, Severe Neutropenia, with 3.1%. It does not connect that term to a specific group or provide event-level details in the information available. The percentage should therefore be read as a registry listing, not as a group-specific risk estimate or as a basis for comparison.

Other adverse events are recorded for 29 of 29 people at risk in the l-THP group and 32 of 32 in the sugar-pill group. The registry does not define the scope of this category or provide the event types and severity details needed to interpret these counts. Serious and other adverse-event counts are distinct registry entries; they should not be treated as interchangeable measures.

The event counts are small, and the record does not report confidence intervals, statistical comparisons, exposure duration, or complete event descriptions. Accordingly, the figures are best read as the safety counts recorded, with substantial limits on comparative interpretation.

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

The registry record identifies a clinical question: whether symptom outcomes differed between people assigned to l-THP and those assigned to a sugar pill, with assessment at baseline and 4 weeks (endpoint). It documents randomization, quadruple masking, a parallel-group design, and enrollment of 63. It also records the intervention dose as 30 mg BID and lists improvement in cognitive function as a secondary outcome.

What the record does not establish is the answer to the primary question. It contains no symptom means, changes, between-group estimates, confidence intervals, or p-values. Thus it cannot show the direction or size of a symptom difference, whether the estimate is precise, or how compatible the results are with effects of different magnitudes. Completion status does not fill this gap.

The record also does not establish that the treatment was beneficial or harmful. Descriptions of the drug’s proposed pharmacological properties are part of the trial rationale, not clinical outcome evidence. Likewise, the limited adverse-event counts do not establish comparative safety, especially without group-linked detail for the listed serious event term, event descriptions, exposure information, or uncertainty estimates.

General interpretation: absence of a posted estimate is not evidence that groups were the same, and it is not evidence of a difference. A null or inconclusive result would require outcome data and an analysis; neither is reported for the primary endpoint. The missing statistical details also prevent appraisal of analysis populations, missing data, or multiplicity.

The most defensible reading is therefore limited: the registry record documents a completed randomized trial with a stated symptom-outcome question and brief safety counts, but it does not provide the comparative primary results needed to judge the magnitude or precision of any effect.

13. Why This Trial Matters Statistically

This trial is statistically notable because its design description and outcome question are clearer than its posted comparative results. Randomization, quadruple masking, a parallel-group model, and a 4-week endpoint identify important features of the intended comparison. Yet no primary outcome estimates or uncertainty measures are reported. The distinction between knowing how a trial was designed and knowing what it found is central to sound statistical interpretation.

The primary outcome is described through several symptom measures and categories. A composite or multi-measure outcome can be difficult to interpret unless its components, scoring, and analysis priority are clear. The record names the BPRS positive symptom subfactor, SANS, and BNSS, while also including a description of the total BPRS score. It does not clarify how those pieces relate to the primary analysis. That ambiguity makes a single summary of the intended endpoint difficult to reconstruct.

The record also illustrates why outcome denominators and analysis populations matter. Enrollment is 63, while the safety entries give separate at-risk counts. Without participant flow and outcome-specific denominators, readers cannot determine who contributed to each analysis. Missing-data methods and multiplicity handling are also not reported, limiting assessment of robustness and reproducibility.

Finally, safety counts need contextual interpretation. A count alone does not show causation, and a listed serious event term without a group assignment cannot support a direct comparison. Statistical reporting is most useful when it pairs event counts with clear definitions, denominators, and uncertainty. These limitations make the registry informative about the question and design, but insufficient for evaluating a treatment effect.

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 key limitation is that the registry record does not report primary outcome results. It provides no group-level scores, change estimates, treatment contrast, confidence interval, or p-value. As a result, neither effect magnitude nor precision can be assessed.

The outcome description is not fully operationalized. It names the BPRS positive symptom subfactor, SANS, and BNSS, while also describing the total BPRS scoring range and direction. The record does not specify which measure defined the primary analysis, whether measures were analyzed separately, or how endpoint values were compared with baseline. The primary outcome is noted as involving several categories or time points, without one comparison being selected in the posted information.

Participant flow is not reported. Although enrollment is 63, the record does not state how many were randomized to each arm, completed the 4-week assessment, or contributed to each symptom analysis. It does not report withdrawal reasons, adherence, missing outcomes, or missing-data methods. The adverse-event denominators cannot resolve these questions about efficacy analyses.

Important design and analysis details are also absent: eligibility criteria, baseline characteristics, randomization method, allocation concealment, the roles masked, the statistical model, prespecified multiplicity procedures, and analysis populations are not reported in the registry record. Interim analyses and the trial’s own sample-size justification are also not reported in the registry record.

Safety interpretation is limited by sparse event information. The record lists serious-event counts and deaths but does not give a group assignment for the listed Severe Neutropenia term or provide fuller event descriptions and uncertainty. These limitations restrict interpretation of both efficacy and safety and prevent independent reconstruction of the trial’s main comparative findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity — NCT02118610.
• Registry record last updated 2022-01-06; status last verified 2022-01.
• Results first posted 2020-04-07.
• 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

NCT02118610 is recorded as a completed, randomized, quadruple-masked, parallel-group trial sponsored by the University of Maryland, Baltimore. It lists schizophrenia as the condition and enrollment of 63. The recorded start is 2014-09, and primary completion is 2018-12. Phase is listed as NA.

The interventions were L-tetrahydropalmatine (l-THP), described as 30 mg BID, and a sugar pill. The primary outcome is titled Positive and Negative Symptom Improvement, with BPRS positive symptom subfactor, SANS, and BNSS measurements at baseline and 4 weeks (endpoint). Improvement in cognitive function is listed as a secondary outcome.

The registry record does not report a primary outcome estimate or analysis details sufficient to assess its precision. Safety entries list serious adverse events in 0 of 29 people at risk in the l-THP group and 1 of 32 in the sugar-pill group; deaths are 0 in each group. The listed serious adverse-event term Severe Neutropenia is 3.1%, without a group assignment in the record.