Glutamate Reducing Interventions in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Glutamate Reducing Interventions in Schizophrenia (NCT03321617), a randomized phase 1 study. The primary outcome is Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14.

2. Clinical Question

3. Trial Design

The registry describes this as a phase 1, randomized, triple-masked, parallel-design study. It is marked completed, with an enrollment of 16. The listed study dates run from April 17, 2018, to March 13, 2020, the primary completion date. The record identifies New York State Psychiatric Institute as the sponsor.

Four POMA dose arms are listed. Participants in each arm were to take the assigned dose twice a day for 14 days. The arm descriptions specify 40mg, 80mg, 120mg or 160 mg per dose, with the corresponding twice-daily amounts included in the arm labels. The record does not explain how randomization was generated, how allocation was concealed, or which people were masked. Those details are not reported in the registry record.

The primary endpoint was a continuous measure: mean percentage change in left hippocampal CA1 region CBV from baseline to Day 14. The endpoint population is stated to include participants who completed both scans. The posted arm counts for this endpoint are 2, 3, 2 and 2, respectively, for the four dose arms. These endpoint counts are not the same as the enrollment figure, and the registry record does not explain the difference.

The record lists one outcome measure and no posted analyses. It does not give a detailed protocol, a sample-size justification, or a statistical analysis plan. In particular, the record does not state how the four dose groups were intended to be compared, whether dose was to be analyzed as a category or trend, or how the masking and randomization procedures were implemented. The randomized design is part of the registry description; it does not by itself establish what analysis was performed on the posted outcome summaries.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 5 participants consented to the protocol and underwent screening procedures but were not randomized (did not receive study medication). Reasons for screen fail: 1-withdrew consent 1-unable to undergo scan 3-study was paused due to COVID-19 pandemic

Overall Study

Analysis population for the primary outcome, as defined in the registry: participants who completed both baseline and Day 14 scans

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.

Population: participants who were randomized (received at least one dose of POMA).

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14, measured over Baseline to 14 days of POMA/placebo.

The primary endpoint is percentage change in CBV in the left hippocampal CA1 region, comparing the baseline scan with the Day 14 scan after 14 days of POMA or placebo, as described in the outcome timeframe. The registry specifies the mean as the summary measure and standard deviation as the measure of spread. The outcome population consists of participants who completed both scans.

CBV is an imaging measure. The study summary says MRI was used to examine whether POMA doses affect glutamate levels, while the named primary outcome is change in CBV. These are not interchangeable descriptions: the posted endpoint is CBV percentage change, not a directly reported glutamate concentration. The registry record does not describe the MRI acquisition or analysis in enough detail to explain how CBV was intended to relate to glutamate.

Percentage change puts the endpoint on a scale relative to each participant’s baseline value. This can make within-participant change the focus rather than the absolute CBV value at Day 14. As a general statistical point, a mean conveys the central tendency of the observed changes, while a standard deviation describes their variability. Neither summary alone shows the precision of an estimated treatment contrast. The registry record does not post confidence intervals or a defined inferential comparison for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry names the mean and standard deviation as its summary statistics. For a continuous outcome, the mean is the arithmetic average of the observed measurements. The standard deviation describes how dispersed individual measurements are around that average. These quantities answer different descriptive questions: the mean indicates the center of the observed values, and the standard deviation indicates their spread. They do not, on their own, establish whether groups differ beyond what could arise through sampling variation.

What does a group mean tell the reader?

Here, each mean summarizes percentage changes in left hippocampal CA1 CBV among participants in one dose arm who completed both scans. A positive mean indicates an average increase from baseline on the outcome’s percentage-change scale; a negative mean indicates an average decrease. That direction describes the posted sample summary, not a treatment effect relative to a comparator. To estimate a comparative effect, an analysis would need to define a contrast between groups and quantify uncertainty around it. The registry record does not post such a comparison.

How should the standard deviation be read?

General statistical explanation: standard deviation measures variability among observed values, whereas a confidence interval expresses uncertainty about an estimated quantity, such as a mean or a difference between means. A small standard deviation does not guarantee a precise estimate of a group contrast, particularly when the group contains very few observations. Conversely, a standard deviation is not a confidence interval and should not be interpreted as one. The registry does not report confidence limits for the primary endpoint.

There is also an important distinction between variability among participants and precision of an estimated treatment difference. A treatment comparison depends on the variability and number of observations in the relevant groups, and on the analysis used. The posted arm summaries do not supply a standard error or interval for any two-arm contrast. The record states that values for a two-arm comparison were missing or not estimable, so a reader cannot infer a sponsor-reported comparative estimate or test from the available summaries.

What does randomization contribute?

General statistical explanation: random assignment can help make treatment groups comparable at the start of a study, because assignment is not chosen according to participants’ measured or unmeasured characteristics. It does not ensure that groups with very few participants will be balanced, and it does not replace an appropriate analysis. The registry identifies the study as randomized, but does not report the sequence-generation method, concealment procedure, or an analysis that accounts for assignment. The record also does not specify whether the planned primary comparison was between each dose and the designated control or followed another approach.

The study is labeled triple-masked, but the registry does not identify the three masked parties or give details about how masking was maintained. Masking can reduce the risk that expectations influence care, measurement or assessment, depending on who is masked and how the outcome is collected. Those general benefits cannot be evaluated for this record without implementation details. The primary measure is based on MRI, but the record does not explain the acquisition, processing or review procedures.

Why do the small endpoint counts matter?

The posted endpoint counts in the four arms are 2, 3, 2 and 2. These small counts mean that each participant contributes substantially to the group summary. In general, estimates from small groups tend to be less stable, and uncertainty can be considerable even when a mean appears far from zero. The record does not provide confidence intervals or participant-level values to quantify that uncertainty. A visual impression of differences among means should therefore not be treated as a formal test.

The enrollment figure is 16, while the endpoint summaries include only participants who completed both scans. A randomized study can have different counts for enrollment, treatment exposure, safety assessment and outcome analysis. Which participants were excluded from the primary endpoint, why they were excluded, and how missing scans were handled are not reported in the registry record. It is therefore not possible to determine from the record whether the primary summaries reflect all randomized participants or only a subset selected by scan completion.

What can be learned from the planning assumptions?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It also describes considering effects at a stated fraction of the observed effect. Such planning calculations estimate the participant count that might be needed under specified assumptions; they are not observed power and do not establish how the trial was designed. No numerical planning outputs are reported in the registry record. The trial’s own sample-size justification and assumptions are not reported.

General statistical explanation: a planning calculation depends on the chosen outcome, target effect, variability, significance level, allocation, and analysis assumptions. If an observed effect from a small study is used as a planning input, that estimate may be unstable. A planning illustration is not a retrospective demonstration that the completed study had adequate power. It also cannot compensate for the absence of a posted inferential analysis. The registry record does not state whether interim analyses were planned or conducted, and no such details should be inferred from the posted summaries.

Finally, no model or analysis procedure is posted for the primary endpoint. It is not reported whether an analysis adjusted for baseline CBV, used a repeated-measures approach, or accounted for any additional factors. Those methods can affect the estimate and its uncertainty. Without a reported analysis plan and results, the safest statistical reading is to treat the arm means and standard deviations as descriptive summaries only.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no secondary outcomes posted. It also lists zero analyses. A single listed outcome does not establish that only one hypothesis was examined: the record does not provide a complete statistical analysis plan, nor does it say whether multiple dose comparisons, time points or imaging measures were considered elsewhere. A multiplicity adjustment or strategy is not reported in the registry record.

The primary outcome population is defined as participants who completed both baseline and Day 14 scans. This is a scan-completer population, rather than an explicit statement that all randomized participants were included. The record does not report how many participants lacked one or both scans, why scans were unavailable, or whether any missing values were imputed. It also does not describe sensitivity analyses for missing outcome data.

The enrollment figure is 16, while the primary outcome arm counts are 2, 3, 2 and 2. The registry record does not explain the difference between enrollment and the counts contributing to the posted endpoint summaries. The safety denominators also differ by arm from the posted endpoint counts. This may reflect different analysis populations or assessment availability, but the reason is not reported and cannot be determined from these summaries.

The record does not identify an intention-to-treat analysis, a per-protocol analysis, or another analysis population for the primary outcome. It also does not report whether participants were analyzed in the groups to which they were randomized. These omissions limit assessment of missing-data bias and of the relationship between randomization and the reported summaries.

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 non-serious adverse event terms

The registry reports no serious adverse events affecting participants in any of the four listed POMA arms, and no deaths are reported in those arms. The serious-event risk counts are 3, 3, 2 and 3 for the dose arms, respectively. These are the denominators for the serious adverse event summaries; they should not be replaced by the enrollment figure or the primary outcome counts.

Other adverse events affected 1, 3, 1 and 2 participants in the respective arms, with risk counts of 3, 3, 2 and 3. These are descriptive counts for the groups and are not comparative estimates. The registry does not provide event-level detail for these other events in the posted safety information, so their nature, severity and timing cannot be assessed from these counts.

A count of zero serious adverse events in a small group does not establish that serious events cannot occur or that a treatment is safe more broadly. General statistical explanation: when few participants are observed, uncommon outcomes may not appear even if the underlying risk is not zero. The registry record does not report further details about safety monitoring, definitions, follow-up beyond the study period, or statistical comparisons of adverse events.

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

The record establishes that the study was registered as a randomized, triple-masked, parallel phase 1 trial of four POMA dose levels in people at clinical high risk for psychosis. It reports mean changes in left hippocampal CA1 CBV among participants who completed baseline and Day 14 scans. The means are positive in two arms and negative in two arms, rather than forming a consistent direction across the dose levels. The record does not provide a formal dose comparison or an estimate against placebo.

These summaries do not establish whether POMA changes CBV relative to a control, whether any observed difference is statistically reliable, or whether a higher dose is associated with a larger effect. They also do not directly establish an effect on glutamate concentration: the named primary endpoint is CBV percentage change, and a direct glutamate outcome is not reported. No confidence intervals or comparative tests are posted to show the precision of the results.

The small endpoint counts and the absence of a reported analysis plan are important when interpreting the means. Individual observations can have considerable influence in groups of this size. The registry does not explain why the endpoint counts differ from enrollment, how missing scans were handled, or which analysis population was intended. It is therefore not possible to judge from the posted summaries whether the analyzed participants represent all randomized participants.

The safety entries report no serious adverse events or deaths among the participants counted in the listed arms, and they report other adverse events in each arm. These counts describe the registry safety record; they do not provide a broad assessment of safety or a comparison of risks. The record does not report detailed event descriptions or longer-term follow-up.

Overall, the posted data are descriptive and limited. They document a small set of arm-level imaging summaries and safety counts, but they do not establish a comparative treatment effect, a dose-response relation, or the precision of an effect estimate. The registry record does not report enough information to draw stronger statistical conclusions.

13. Why This Trial Matters Statistically

This study illustrates a common distinction in early clinical research: a biologically motivated question and a registered outcome are not necessarily the same measurement. The registry summary describes using MRI to examine whether POMA doses affect glutamate levels, while the named primary endpoint is percentage change in left hippocampal CA1 CBV. Keeping that distinction clear prevents an imaging outcome from being described as though it were a direct measurement of glutamate.

It also demonstrates why the form of the posted result matters. Arm-specific means and standard deviations can describe observed data, but they do not answer a comparative question without a defined contrast and an estimate of uncertainty. The record identifies one arm as the control, yet the listed arms are all POMA doses and no placebo arm appears in the arm list. The description of the comparison is therefore important to interpreting what the results can address.

The endpoint counts are small, which makes precision and missing-data reporting especially consequential. The record defines the endpoint population by completion of both scans but does not explain the difference between enrollment and endpoint counts. Without that information, readers cannot assess how selection into the scan-completer population may shape the summaries.

Finally, the record lists no analyses and provides no inferential comparison. This is a reminder that randomization and masking labels do not substitute for a reported analysis plan and result. Clear reporting of the intended contrast, analysis population, missing-data handling and uncertainty would be needed to support stronger statistical interpretation. The available record is useful for identifying the design and descriptive outcome summaries, while leaving those inferential questions unresolved.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation is the small number of participants contributing to the primary endpoint in each arm: 2, 3, 2 and 2. With so few observations, arm means can be unstable and uncertainty may be substantial. The record posts no confidence intervals or formal tests for the primary outcome, so the precision of the summaries and the evidence for between-arm differences cannot be assessed.

The primary outcome is restricted to participants who completed both baseline and Day 14 scans. The enrollment figure is 16, but the registry does not explain why the endpoint counts are smaller or report the reasons for missing scans. It is not reported whether missing outcomes were imputed, whether sensitivity analyses were done, or whether the analysis included all randomized participants. This leaves possible selection effects unresolved.

The comparator information is also limited. The registered control is the 40mg BID POMA arm, while the other listed arms are higher POMA doses. The registry summary timeframe refers to POMA/placebo, but no placebo arm is listed in the posted arms. The record does not clarify this discrepancy, and the two-arm comparison is reported as missing or not estimable.

Further methodological details are not reported in the registry record. These include the randomization procedure, the identities of the masked parties, the planned analysis model, the sample-size justification, multiplicity handling, and any interim analyses. The record does not provide participant-level observations, detailed MRI methods, or detailed descriptions of other adverse events. These omissions limit assessment of the outcome measurement, potential bias, statistical uncertainty and safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Glutamate Reducing Interventions in Schizophrenia — NCT03321617.
• Registry record last updated 2021-12-01; status last verified 2021-11.
• Results first posted 2021-12-01.
• 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 completed study is registered as a randomized, triple-masked, parallel phase 1 trial sponsored by New York State Psychiatric Institute. It enrolled 16 participants with clinical high risk for psychosis and assigned participants to one of four twice-daily POMA dose arms for 14 days.

The primary outcome is mean percentage change in left hippocampal CA1 CBV from baseline to Day 14 among participants who completed both scans. Posted endpoint counts are 2, 3, 2 and 2 across the four arms. The record lists one outcome measure and no analyses. It does not report a formal comparative result, confidence intervals, or an analysis plan.

No serious adverse events or deaths are reported in the listed arms. Other adverse events are reported in each arm. The record does not explain the difference between enrollment and the endpoint counts, or provide details sufficient to assess missing outcomes, the comparator inconsistency, or the precision of the imaging summaries.