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 Ketamine Treatment Effects on Synaptic Plasticity in Depression (NCT04091971), a na phase 4 study. The primary outcome is Synaptic Density.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04091971 |
| Phase | Phase 4 |
| Condition | Major Depressive Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | New York State Psychiatric Institute |
| Results posted | Yes |
2. Clinical Question
Population
Adults with current major depressive disorder (MDD) who completed PET imaging before and after a course of ketamine infusions. The registry record lists an enrollment of 9, but does not report how many participants completed both scans or contributed to the primary analysis.
Intervention
Ketamine, given as 4 sequential intravenous infusions over a two-week period. The primary endpoint description places the post-treatment PET scan 24-48 hours after the final infusion.
Comparator
There is no separate control group in the registry record. This is a single-group study, with synaptic density assessed before and after treatment. The record lists allocation as NA and masking as none.
Primary question
How does PET-measured synaptic density in the medial prefrontal cortex compare before and after ketamine treatment? The registry record describes the planned measurement but does not report a numerical estimate of the change, its variability, or an inferential analysis.
The study is focused on a biological measure rather than a direct comparison of treatment strategies. Its stated purpose is to examine synaptic density before and after ketamine and to investigate ketamine's mechanism of action. The registry summary also describes an interest in biomarkers that might predict treatment outcome. Those aims provide context, but the posted record does not report a biomarker-prediction result.
Because each participant is assessed at baseline and after treatment, the intended comparison is within the same group over time. That structure can describe how the PET measure changes across the assessment periods among participants with available measurements. It cannot, by itself, separate a treatment-associated change from changes that might occur over time for other reasons. No randomized or concurrent control comparison is described.
3. Trial Design
The registry identifies this as a completed Phase 4 study with a single-group model. The recorded enrollment is 9. The listed condition is major depressive disorder, and the intervention is ketamine. The group description specifies depressed adults with current MDD and describes 4 sequential intravenous infusions over a two-week period.
The design uses a pre-treatment and post-treatment PET assessment, rather than a comparison between separate treatment arms. The baseline scan was to be acquired as close as possible before the first infusion, up to 7 days before it. The post-treatment scan was to be acquired 24-48 hours after the final infusion. These timings define the intended measurement windows; the registry record does not report individual scan dates or whether all participants followed those windows.
Allocation is listed as NA, masking as none, and the model as single group. Thus, the record does not describe random assignment or a blinded control group. The intervention group description is the only treatment-group description posted by the registry record.
The study start date is 2020-10-09, and the primary completion date is 2022-05-01. Its status is listed as completed. A completed status describes the registry's study status; it does not establish that every enrolled participant completed treatment, PET imaging, or the analysis. Participant flow and the number included in the endpoint analysis are not reported in the registry record.
The primary outcome is synaptic density measured by PET. The registry also lists the 17-item Hamilton Depression Rating Scale as a secondary outcome. Although the record indicates 2 outcome measures, it lists 0 analyses. Numerical outcome results and details of the statistical analysis are not reported in the registry record.
The registry names the New York State Psychiatric Institute as sponsor. It does not report a control treatment, a masking procedure, or an allocation procedure. The one-group, pre-post structure is important when interpreting any observed difference: a change over time in the measured group is not the same as an effect established by a controlled comparison.
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 | Depressed Adults With Current MDD |
|---|---|
| STARTED | 9 |
| COMPLETED | 5 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Depressed Adults With Current MDD |
|---|---|
| Withdrawal by Subject | 1 |
| No longer met eligibility criteria after enrollment. | 2 |
| Panic attack during MRI; no MRI or PET but completed ketamine and other procedures | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants with MDD who completed PET imaging pre-post a course of ketamine infusions for depression
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: Including only participants who completed research procedures beyond initial screening and consent (n=6: 5 completers and 1 participants with clinical outcomes but not PET)
| Characteristic | Unit | Depressed Adults With Current MDD |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 37.33 (SD 3.83) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Synaptic Density, measured over Measured at two time frames: Time frame 1 = Baseline. Time frame 2 = post-treatment.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Ratio |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is synaptic density, expressed as a ratio, measured with PET imaging using the radiotracer [11C]UCB-J. The registry describes [11C]UCB-J as a marker of synaptic density and specifies the medial prefrontal cortex as the brain region for quantification. It identifies the measure as binding potential, BPND, defined as the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue.
The same endpoint is intended to be assessed at baseline and after treatment. The baseline scan was scheduled as close as possible before the first ketamine infusion, up to 7 days beforehand. The post-treatment scan was scheduled 24-48 hours after the final infusion. This paired timing is intended to capture within-participant differences in the PET measure across the treatment period.
The endpoint is used to investigate a biological question: whether PET-measured synaptic density differs between the two assessment times. The registry summary explains that [11C]UCB-J targets SV2A, a protein present in presynaptic vesicles, and describes PET as a way to measure synaptic connections in the living brain. The record states that previous studies found lower binding in patients with more severe depression, but it does not provide those studies' results or establish a clinical interpretation for this trial's endpoint.
A numerical baseline value, post-treatment value, within-participant change, standard deviation, confidence interval, or test result is not reported in the registry record. The posted information therefore describes what was measured and when, but does not quantify the endpoint outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the rationale, design, endpoint definition, and assessment schedule, but not the numerical primary-outcome results. It does not report the mean synaptic-density value at either time point, the mean within-participant change, a standard deviation, a confidence interval, or a p-value. Consequently, the direction, size, and precision of any change cannot be described from the record.
The endpoint is a continuous PET measure summarized in the registry as a mean with standard deviation. In general, a mean describes the central value of a measurement, while a standard deviation describes how dispersed individual measurements are around that mean. Neither summary is available for this endpoint in the registry record. Without them, the scale and variability of the observed measurements are unknown.
In general, a confidence interval indicates the range of values compatible with a statistical estimate under the assumptions of the analysis. It helps distinguish a relatively precise estimate from one with substantial uncertainty. No confidence interval is reported for the primary endpoint, so the precision of a treatment-period change cannot be assessed. The absence of a reported interval is not evidence that the underlying effect is either small or large.
This is a single-group pre-post study, not a randomized comparison. In general, measuring participants before and after an intervention can reveal a temporal pattern in the observed group, but without a concurrent control group it cannot isolate the intervention as the cause of that pattern. Other changes over time, measurement variation, and participant-level factors may also contribute. The registry record does not report an analysis that addresses these issues.
The enrollment is listed as 9, but the analysis population and the number of participants with both PET assessments are not reported. It would therefore be inappropriate to assume that all enrolled participants contributed to the endpoint. No participant-level data or analysis estimates are available in the record to clarify this point.
The registry describes an aim to examine ketamine's mechanism and identify biomarkers that could predict outcome. Those are research aims, not reported findings. The record does not report a biomarker model, predictive performance, or an analysis linking changes in PET binding to depression outcomes. It also does not report numerical results for the listed secondary outcome, the 17-item Hamilton Depression Rating Scale.
Safety counts are reported separately: the group record lists 0 serious adverse events, 5 participants affected by other adverse events, and 0 deaths. Those counts do not provide information about the primary PET endpoint and should not be treated as an estimate of treatment effect.
9. Statistical Methods Explained
The record describes a continuous primary endpoint measured at two time frames: baseline and post-treatment. The endpoint is PET-measured [11C]UCB-J binding potential, BPND, in the medial prefrontal cortex. The registry identifies the summary parameter as a mean and the dispersion measure as a standard deviation. It does not report the actual means, standard deviations, or a calculated comparison between the time frames.
What does a within-participant comparison mean?
In general, a within-participant comparison uses measurements from the same person at different times. For a pre-post outcome, the relevant quantity is each participant's post-treatment measurement relative to that participant's baseline measurement. An average of those individual changes can describe the group's mean change, while the spread of individual changes conveys how consistently participants changed. This approach differs from comparing the mean of one group with the mean of an independent group. The registry record does not state how the paired measurements were analyzed or provide an estimate of their change.
The paired structure can account for stable differences between participants when estimating change, because each person serves as their own reference. It does not, however, create a control group. In general, a pre-post comparison alone cannot determine how much of an observed change is attributable to the intervention rather than other time-related influences. The registry record lists no randomized comparator or masking.
What do a mean and standard deviation describe?
In general, the mean is the arithmetic average of the observed measurements. The standard deviation describes how spread out the measurements are around that average, in the same units as the measure. For a paired analysis, the standard deviation of participant-level changes is distinct from the standard deviations at baseline and post-treatment. The record names standard deviation as the dispersion measure but does not provide any of these numerical summaries.
In general, a confidence interval expresses uncertainty around an estimate and depends on the estimate's variability and the analysis assumptions. A p-value addresses compatibility of the data with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No test statistic, model specification, or covariate adjustment is reported either.
What do the planning assumptions mean?
The registry's planning description says that sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. It also distinguishes total event counts for time-to-event calculations from participants per arm for other calculations. These are planning assumptions, not a description of the study's single-group pre-post design. Numerical planning outputs and the fraction of the observed effect are not reported in the registry record.
In general, a sample-size illustration estimates the amount of information a hypothetical design might need under specified assumptions. It is not the number analyzed in the completed study and is not observed power. A planning calculation based on an observed effect also depends on that effect estimate, but the primary endpoint estimate is not reported in the registry record. The record does not report the study's own sample-size justification, or whether these illustrations informed its design.
What is not described about the analysis?
The registry lists 0 analyses. It does not report a prespecified statistical analysis plan, a method for handling missing PET measurements, a transformation of the PET endpoint, or an approach to outliers. It also does not report whether the analysis included all enrolled participants, only those with both scans, or another analysis population. These omissions prevent assessment of how the planned endpoint was converted into a statistical result.
In general, repeated measurements can be analyzed with paired methods or models that account for the relationship between observations from the same participant. The appropriate method depends on the data structure, assumptions, and estimand. Over-dispersion is a concern in some count-data models when variability exceeds a model's assumptions; it is not a reported feature of this continuous PET endpoint. The registry record does not describe a count model or an over-dispersion adjustment.
Without numerical results and an analysis description, no recalculation from summary statistics is possible. The registry does not report a sponsor analysis or a recalculated estimate to compare. Any interpretation must therefore remain at the level of the stated design, endpoint, and reported safety counts, rather than inferential evidence about change in synaptic density.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies synaptic density as the primary outcome and the 17-item Hamilton Depression Rating Scale as a secondary outcome. It also reports 2 outcome measures and 0 analyses. Numerical results for either outcome are not reported in the registry record.
Multiplicity refers, in general, to the added chance of a false-positive finding when multiple hypotheses or outcomes are tested. A statistical plan may specify which outcome is primary, how secondary outcomes are interpreted, and whether any adjustment is used. The record does not report a multiplicity strategy, the number of hypotheses tested, or any outcome-specific analyses. The presence of a named primary and secondary outcome does not by itself show how multiple testing was handled.
Missing-data methods are also not reported. The endpoint description specifies two assessment times, but the registry record does not provide participant flow, the number with both scans, reasons for missing measurements, or an imputation or sensitivity-analysis method. The enrollment of 9 should not be treated as the number included in the endpoint analysis because the analysis population is not reported.
The analysis population is not described. The record does not say whether analyses were based on all enrolled participants, participants who received treatment, participants who completed both PET assessments, or another defined group. It also does not report exclusions or protocol deviations.
In general, these details matter because incomplete observations and analytic choices can affect the estimate and its uncertainty. With no reported outcome estimates, analysis population, missing-data approach, or multiplicity plan, the robustness of any endpoint finding cannot be evaluated from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Depressed Adults With Current MDD | 0 | 9 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Depressed Adults With Current MDD | 0 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Depressed Adults With Current MDD | 5 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Depressed Adults With Current MDD |
|---|---|---|
| Excessive Sweating | General disorders | 3 of 9 |
| Decreased appetite | Gastrointestinal disorders | 3 of 9 |
| Insomnia | Nervous system disorders | 2 of 9 |
| Drowsiness | Nervous system disorders | 2 of 9 |
| Irritability | Nervous system disorders | 2 of 9 |
| Memory difficulties | Nervous system disorders | 2 of 9 |
| Headache | Nervous system disorders | 2 of 9 |
| Ringing in Ears or Trouble Hearing | Ear and labyrinth disorders | 2 of 9 |
| Frequent need to urinate | Renal and urinary disorders | 2 of 9 |
| Hair thinning/loss | General disorders | 2 of 9 |
The registry lists safety information for the group titled “Depressed Adults With Current MDD.” The serious-adverse-event count is 0 among 9 at risk, and the death count is 0. For other adverse events, 5 are listed as affected among 9 at risk. The record does not list serious adverse-event terms.
These are counts recorded in the registry, not estimates of a comparative risk difference. Because the study has a single group and no concurrent control group, the listed counts do not show how safety outcomes compare with another treatment or with no treatment. The registry record does not provide event descriptions for the other adverse events, their timing, severity, relationship to treatment, or the number of events per affected participant.
In general, a count of zero recorded serious events does not establish that an event is impossible or that risk is absent. It describes what was recorded for this group within the registry's reported safety fields. Likewise, the other-adverse-event count should not be converted into a percentage or treated as a measure of comparative safety. These counts are separate from the primary PET endpoint and do not explain whether synaptic density changed.
12. What the Result Does, and Does Not, Mean
The study asks a focused biological question: whether PET-measured synaptic density in the medial prefrontal cortex differs between baseline and the period after a course of ketamine infusions. The registry describes the radiotracer, the endpoint, and the intended scan timing. It does not report a numerical result for that comparison, so no direction or magnitude of change can be stated.
The record's stated goals include examining ketamine's mechanism of action and identifying biomarkers that could predict treatment outcome. Those goals describe the motivation for the research. They should not be read as evidence that the mechanism was confirmed or that a predictive biomarker was identified. The registry does not report numerical findings for either aim.
The study's design also sets limits on interpretation. A single-group pre-post comparison can describe a measured change among participants with observations at both times, but it cannot by itself establish that treatment caused the change. There is no randomized comparator in the registry record, and allocation is listed as NA. Masking is listed as none.
The record does not report the primary estimate, its standard deviation, a confidence interval, a p-value, or the number included in the endpoint analysis. As a result, statistical precision and compatibility with different effect sizes cannot be assessed. The listed enrollment does not resolve this uncertainty about the analysis population.
Safety information is limited to registry counts: 0 serious adverse events, 5 affected by other adverse events, and 0 deaths. Those figures are descriptive for the recorded group and do not provide a controlled comparison. The listed secondary outcome is the 17-item Hamilton Depression Rating Scale, but numerical results for it are not reported.
In short, the registry record documents a small, single-group investigation of a PET measure with pre-treatment and post-treatment assessments. It supports describing the research question and measurement approach, but not a conclusion about the size, precision, cause, or clinical significance of a change.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of a mechanistic, within-group study whose main outcome is a continuous imaging measure. Its focus differs from a randomized treatment comparison: the central question is about a measured biological feature before and after treatment. The design and endpoint therefore need to be kept distinct from evidence about comparative clinical outcomes.
The repeated-measure structure makes the participant-level pairing important. In general, baseline and post-treatment values from the same person are related, and analysis of their changes should account for that relationship. Reporting only separate group averages, if that were done, would not necessarily convey the variability of the paired changes. The registry record does not report the analysis or numerical summaries needed to evaluate this issue.
The record also illustrates why endpoint definition and result reporting are both necessary. It identifies the PET tracer, target measure, brain region, and scan timing in detail. However, without an estimate and measure of uncertainty, readers cannot judge the amount or precision of any observed change. A well-described measurement protocol is not a substitute for a reported outcome analysis.
The single-group design is another important statistical feature. In general, pre-post measurements can describe temporal change but do not supply the counterfactual comparison needed to isolate treatment effects. A concurrent control group and randomization can address some alternative explanations, but neither is described in this registry record.
Finally, the stated interest in biomarkers raises a distinction between mechanistic measurement and prediction. In general, a candidate biomarker's predictive value requires an analysis that relates the biomarker to an outcome and evaluates how well it predicts that outcome. No such analysis is reported in the registry record. The listed study aims should therefore remain separate from claims about demonstrated predictive performance.
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 for interpretation is that the registry record does not report numerical primary-outcome results. There is no baseline or post-treatment mean, estimate of within-participant change, standard deviation, confidence interval, or p-value. The size and precision of any change cannot be assessed.
The single-group design has no concurrent control comparison. A pre-post pattern, if reported, would not alone establish that ketamine caused the change. Allocation is listed as NA, masking as none, and the model as single group.
The record lists enrollment of 9 but does not report how many participants completed both PET assessments or were included in the primary analysis. It does not describe missing observations, participant exclusions, protocol deviations, or the analysis population. The timing windows are specified, but actual scan timing and adherence are not reported.
The registry lists a secondary depression-rating outcome but does not report its results. It also does not report the statistical analysis plan, the methods used to analyze repeated measures, a multiplicity approach, or details of missing-data handling. These gaps limit assessment of analytic choices and the reliability of any endpoint finding.
The safety information is limited to group counts. Serious-event terms are not listed, and descriptions, timing, severity, and treatment relationship for other adverse events are not reported. With no control group, the safety counts are not comparative estimates.
The stated biomarker and mechanism aims are not accompanied by reported analyses or results. No conclusions about biomarker prediction or the mechanism can be drawn from the registry information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ketamine Treatment Effects on Synaptic Plasticity in Depression — NCT04091971.
- Registry record last updated 2023-11-13; status last verified 2023-11.
- Results first posted 2023-11-13.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed Phase 4, single-group study of ketamine in adults with current MDD. Enrollment is listed as 9. The intervention group description specifies 4 sequential intravenous infusions over a two-week period. The study start date is 2020-10-09, and the primary completion date is 2022-05-01.
The primary outcome is PET-measured synaptic density, quantified as [11C]UCB-J binding potential, BPND, in the medial prefrontal cortex. The intended assessments are baseline and 24-48 hours after the final infusion; the baseline scan was scheduled up to 7 days before the first infusion. The secondary outcome is the 17-item Hamilton Depression Rating Scale.
The record lists allocation as NA, masking as none, and 0 analyses. It does not report numerical outcome results, an analysis population, or missing-data methods. Safety counts list 0 serious adverse events, 5 affected by other adverse events, and 0 deaths. These data describe the study record but do not establish a comparative treatment effect.