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 Optimization of VNS in Epileptic Patients to Induce Cardioprotection (NCT04387435), a na na study. The primary outcome is Change in Seizure Frequency or Duration Via a Routine Seizure History Used in Clinical Practice..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04387435 |
| Phase | NA |
| Condition | Epilepsy, Sudden Cardiac Death |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Los Angeles |
| Results posted | Yes |
2. Clinical Question
Population
People with epilepsy who already have an FDA-approved vagus nerve stimulation (VNS) device implanted. The registry record lists epilepsy and sudden cardiac death as conditions relevant to the study.
Intervention
A change or titration in the current or frequency settings of the VNS therapy system, intended to evaluate whether adjusting stimulation parameters can engage cardioprotective effects.
Comparator
There was a single intervention arm and no control arm. The study was non-randomized, and allocation is recorded as NA, so the registry record does not describe a like-for-like comparison group.
Primary question
The primary outcome was change in seizure frequency or duration, assessed through a routine seizure history used in clinical practice following the 4-week VNS treatment phase to the end of the study. The participant completed only the first study visit and did not return.
The clinical question links adjustment of VNS settings to two areas of interest: seizure history and cardioprotection. The stated goal was to evaluate the effects of adjusting stimulation parameters to engage cardioprotective effects in people with epilepsy who already had implanted devices. The primary outcome, however, was a change in seizure frequency or duration, while the listed secondary outcome concerned heart rate and blood pressure responses to several physiological tests.
This was a feasibility study, not a randomized comparison of VNS adjustment with an untreated or alternative-treatment group. The record therefore does not support an estimate of the intervention’s effect relative to a control condition. It also does not report an outcome estimate for the primary question. The participant did not return after the initial visit, leaving no recorded follow-up outcome in the registry summary. The question can be described from the intended intervention and outcome, but the posted record does not establish whether a change in seizure history or cardiovascular response occurred.
3. Trial Design
The registry record describes a prospective, non-randomized study in a single group. Its brief summary specifies participants with epilepsy and previously implanted FDA-approved VNS devices. The intervention was a change or titration in the current or frequency settings of the VNS therapy system. The record lists one intervention arm and an enrollment of 1.
There was no randomized allocation, masking is recorded as none, and the design is listed as single group. No control group is described. Consequently, the design does not provide a concurrent comparison that could separate a response to the setting adjustment from changes over time or other influences. This is important when interpreting an outcome that is intended to change after treatment: without a comparison group, observed changes would not by themselves establish that the adjustment caused them.
The study is marked completed. The registry lists a start date of 2020-12-01 and a primary completion date of 2021-07-07. Its title and official title identify it as a feasibility study focused on optimizing VNS in people with epilepsy to induce cardioprotection. The phase is recorded as NA. The record does not report further details about how participants were selected, how settings were adjusted, or how long each adjustment was maintained.
The primary outcome was change in seizure frequency or duration, assessed using routine seizure history after the 4-week VNS treatment phase through the end of the study. The secondary outcome concerned change in heart rate and blood pressure in response to upright tilt, deep breathing, the Valsalva maneuver, and a cold pressor test. The registry record lists two outcome measures but no analyses. The primary-outcome description states that the participant completed only the first study visit and did not return, which limits what can be learned about follow-up outcomes from this record.
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 | Intervention Arm |
|---|---|
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Intervention Arm |
|---|---|
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: Participant only completed first study visit and did not return
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Intervention Arm |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| 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 | 0 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Seizure Frequency or Duration Via a Routine Seizure History Used in Clinical Practice., measured over Following the 4 - week VNS treatment phase to the of the end of study..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is change in seizure frequency or duration, assessed using a routine seizure history used in clinical practice. Seizure frequency describes how often seizures occur; seizure duration describes how long they last. Tracking these features can provide a clinically familiar way to describe a participant’s seizure history over time. The registry specifies that the outcome was to be assessed following the 4-week VNS treatment phase through the end of the study.
The endpoint is relevant to the study because it records a clinical outcome during a feasibility investigation of VNS setting adjustment. It is distinct from the study’s stated goal of evaluating cardioprotective effects: the primary outcome concerns seizures, while the secondary outcome concerns heart rate and blood pressure responses to physiological tests. Keeping those outcome domains separate is necessary when interpreting what the study was designed to measure.
The registry record does not provide a numerical seizure-frequency or seizure-duration result, a unit, a summary measure, or a measure of variability. Its primary-outcome description says the participant completed only the first study visit and did not return. Therefore, the record does not give a follow-up change to interpret. It also does not report details of the seizure-history assessment, such as the reference period or how a change would be summarized. Those omissions mean the endpoint’s intended clinical meaning can be described, but its observed value and precision cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry lists an enrollment of 1 and states that the participant completed only the first study visit and did not return. The primary outcome is change in seizure frequency or duration after the 4-week VNS treatment phase through the end of the study, but no numerical outcome result is recorded in the registry record for this analysis. The registry also lists zero analyses. Thus, there is no posted estimate of change, no uncertainty interval, and no inferential result to interpret for the primary outcome.
The study’s design also limits what could be concluded even if an outcome change had been available. It is a non-randomized, single-group study with no control arm. A before-and-after change in an individual can be described, but without a concurrent comparator it cannot isolate the effect of setting adjustment from other explanations, including natural fluctuation or changes in circumstances. This is a general limitation of uncontrolled comparisons, not evidence that any particular alternative explanation occurred in this study.
The planned secondary outcome concerns heart rate and blood pressure responses to upright tilt, deep breathing, the Valsalva maneuver, and a cold pressor test. No numerical secondary-outcome results or analyses are listed in the record. The study’s cardioprotection goal should therefore be understood as the aim described in the record, rather than as a demonstrated outcome.
The adverse-event summary records 1 at risk for serious adverse events and 0 affected; for other adverse events it records 1 at risk and 0 affected. It also records 0 deaths. These are counts in a very small registry record and do not establish that the intervention is free of risk. They should be read as recorded event counts, not as precise estimates of event probability.
Overall, the record documents the study’s intended question, intervention, design, outcome definitions, and limited participation. It does not document a completed follow-up assessment or an analyzed clinical effect. The absence of an estimate is not evidence of no change, and the record cannot support a conclusion about whether VNS setting adjustment changed seizure outcomes or cardiovascular responses.
9. Statistical Methods Explained
What does a single-group design tell us?
In a single-group study, participants receive the intervention without a separate control group. Researchers may describe observations during or after intervention, but a comparison with an untreated or alternative-treatment group is not available. If a measurement changes over time, that change alone does not establish that the intervention caused it. General sources of change can include ordinary fluctuation and influences unrelated to the intervention; the registry record does not identify such influences as having occurred in this study.
Here, the registry describes a non-randomized prospective study with one intervention arm and an enrollment of 1. Allocation is recorded as NA, and masking is recorded as none. These design features mean the record does not support a randomized treatment contrast. It also does not report a comparison estimate. The listed primary endpoint is a change in seizure frequency or duration, but the participant did not return after the first visit.
What would an estimate and confidence interval mean?
In general, an estimate is a numerical summary of an observed outcome or contrast. A confidence interval describes uncertainty around an estimate under the assumptions of the statistical method used. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. Neither an estimate nor its interval, on its own, resolves design limitations such as the lack of a control group.
The registry entries do not include a primary-outcome estimate, confidence interval, or measure of variability. They also list no analyses. As a result, there is no numerical estimate whose magnitude or precision can be evaluated. It would not be appropriate to infer a zero effect from the missing result: no follow-up outcome is reported for interpretation.
What does a significance test contribute?
In general, a significance test evaluates how compatible data are with a specified null model, using assumptions about the observations and analysis. A p-value is not the probability that a treatment works, and it does not measure the size or clinical importance of an effect. A statistical test also cannot remedy a missing outcome or create a valid control comparison where none exists.
No p-value or analysis result is listed in the registry entries. The record does not report a statistical plan, model, or test for the primary outcome. Accordingly, there is no basis for describing the primary result as statistically significant or not statistically significant. The same caution applies to the secondary outcome.
Why do missing observations matter?
Missing follow-up information prevents direct assessment of an outcome that depends on later observations. It also matters because missingness can affect the interpretation of results if people with observed and unobserved outcomes differ in relevant ways. General statistical approaches can address missing data under stated assumptions, but those assumptions need to be appropriate and explained. The registry does not report a missing-data method or an analysis population for this study.
The primary-outcome description says the participant completed only the first study visit and did not return. That statement explains why the intended follow-up change cannot be interpreted from the registry entries. It does not establish why the participant did not return, what the participant’s later outcome was, or whether any data were collected outside the recorded visit. Those details are not reported in the registry record.
How should planning calculations be read?
In general, sample-size planning calculations estimate how many observations might be needed under assumed design and effect conditions. They are planning illustrations, not observed outcomes and not evidence of the power achieved by a completed study. Their relevance depends on the assumptions and on whether the assumed effect is credible and applicable to the planned comparison.
The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. Time-to-event illustrations are described as total event counts, while other illustrations are described as participants per arm. These assumptions do not change the actual study design: the registry lists a single group, enrollment of 1, and no randomized comparison. No numerical planning outputs or observed effect estimate are included in the registry record for interpretation. The illustrations therefore cannot be treated as the study’s observed power or as a result of the trial.
More broadly, statistical methods are most informative when the outcome definition, analysis population, model, assumptions, and uncertainty are reported alongside the estimate. The registry entries do not report those details for an outcome analysis. The most defensible reading is therefore descriptive: the record identifies an intended feasibility question and an intervention, but does not supply an analyzed effect estimate for the seizure or cardiovascular outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary outcome of change in seizure frequency or duration and a secondary outcome of change in heart rate and blood pressure responses to physiological tests. When a study examines multiple outcomes or multiple analyses, the chance of finding at least one apparently unusual result can increase if each is tested separately. General approaches to this issue include defining a primary endpoint in advance, specifying the order of testing, or adjusting statistical thresholds. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how this issue was addressed.
The registry lists zero analyses. It does not report a statistical analysis plan, analysis population, missing-data method, or outcome estimates. The primary-outcome description states that the participant completed only the first study visit and did not return. This leaves no reported follow-up primary outcome to interpret and makes the handling of missing observations especially relevant, but the record does not explain any approach to that issue.
General methods for missing data rely on assumptions about why measurements are unavailable and how the unobserved values relate to observed information. The record does not report why the participant did not return or whether any further outcome information was collected. No missing-data assumption or method should therefore be inferred. Nor does the record describe whether analyses were intended to include all enrolled participants, only participants with follow-up, or another analysis population.
These gaps limit assessment of the analysis process, not just the precision of a result. Without a reported analysis plan and outcome data, it is not possible to assess whether outcomes were selected or analyzed as planned, or to evaluate the effect of missingness and multiple outcomes on any inferential claim.
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 |
|---|---|---|---|
| Intervention Arm | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Intervention Arm | 0 of 1 |
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 |
|---|---|
| Intervention Arm | 0 of 1 |
The registry adverse-event summary records 1 at risk for serious adverse events and 0 affected. It records 1 at risk for other adverse events and 0 affected, and 0 deaths. No serious adverse-event terms are listed. These figures describe the counts recorded in the registry; they are not a comparison between treatment groups because the study had a single intervention arm.
With an enrollment of 1 and no reported return after the first visit, the counts should be interpreted cautiously. A count of 0 affected means that no events were recorded in the listed category for the recorded information; it does not show that the intervention has no risk. A small amount of observed information cannot characterize uncommon events or provide a precise estimate of event frequency. The registry entries also do not describe the duration or completeness of safety follow-up, event definitions, or attribution of events to the intervention.
Serious adverse events and other adverse events are separate registry categories. The record does not provide event-level descriptions for either category, and no event terms are listed among the serious events. These data are therefore a limited safety record, not a comprehensive evaluation of safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a feasibility study was conducted to evaluate adjustment of VNS settings in people with epilepsy and previously implanted devices. It identifies a single intervention arm, an intended change in current or frequency settings, a primary seizure-history outcome, and a secondary cardiovascular-response outcome. It also records that the study is completed and that the participant completed only the first visit and did not return.
What the record does not establish is whether VNS adjustment changed seizure frequency or duration, or whether heart rate or blood pressure responses changed. No numerical outcome estimates or analyses are listed. The missing follow-up result should not be interpreted as no change, and no treatment effect can be inferred from the intervention’s stated goal.
Even a reported change in a single-group study would not, by itself, establish that the intervention caused it. Without a control group, there is no concurrent reference for changes that might have occurred over time for other reasons. The design is suitable for describing a feasibility investigation, but the registry entries do not support a controlled estimate of efficacy.
The adverse-event counts are also limited. The registry records no affected participants in the listed serious or other adverse-event categories and no deaths, but the enrollment and follow-up information do not permit a broad safety conclusion. Those counts should not be generalized beyond the recorded study information.
The most accurate conclusion is that this registry record describes the study’s aims and design but contains insufficient outcome information to assess clinical effects. It does not demonstrate cardioprotection, a change in seizure outcomes, or absence of risk. It also does not establish that the intended outcomes were assessed at the planned follow-up point.
13. Why This Trial Matters Statistically
This study is statistically notable because the question links a device-setting adjustment to outcomes in more than one domain: seizure history and cardiovascular responses. The distinction between the study’s cardioprotection goal and its listed primary endpoint matters. The primary endpoint concerns seizure frequency or duration, while the secondary outcome concerns heart rate and blood pressure responses to physiological tests. These outcomes address different aspects of the study and should not be treated as interchangeable evidence.
The registry describes a feasibility study, a single intervention group, and enrollment of 1. Those features make it especially important to distinguish a study’s aim from evidence about an effect. A feasibility investigation can document whether a planned approach was attempted, but an outcome claim requires interpretable observations and a suitable analysis. The registry entries do not include a numerical outcome result or analysis.
The record also illustrates why follow-up and transparent analysis reporting matter. The primary-outcome description says the participant completed only the first study visit and did not return. Without reported follow-up data, there is no estimate of change to assess. Without a reported analysis plan or analysis population, readers also cannot evaluate how outcomes would have been handled or what assumptions would support an inference.
These points are relevant beyond this study. Statistical interpretation depends on the outcome definition, study design, completeness of observation, and the precision of any estimate. The absence of a control group constrains causal interpretation, while missing follow-up limits even descriptive assessment of the intended outcome. In this record, those constraints are central to understanding what can and cannot be concluded.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most direct limitation is the small enrollment recorded in the registry: 1. The primary-outcome description says that the participant completed only the first study visit and did not return. As a result, no follow-up change in seizure frequency or duration is available in the registry entries for interpretation. The record does not explain why the participant did not return or whether outcome information was obtained by another means.
The single-group, non-randomized design has no concurrent control group. Any change, if it had been recorded, could not be separated from changes over time or other influences using a randomized comparison. Masking is recorded as none. The registry does not report further details about how outcomes were assessed or whether the assessment was standardized beyond the description of routine seizure history.
The primary outcome is described, but the record does not report a numerical result, unit, summary parameter, or measure of variability. It lists no analyses. For the secondary cardiovascular outcome, the record names the physiological tests but does not give numerical results or analysis details. The registry also does not report a statistical plan, analysis population, or missing-data method.
Finally, the safety counts are based on the limited recorded study information. Event definitions, safety follow-up details, and attribution are not reported in the registry record. These limitations mean that the record can describe the study’s intent and design, but cannot provide a reliable estimate of clinical effect or a broad characterization of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Optimization of VNS in Epileptic Patients to Induce Cardioprotection — NCT04387435.
- Registry record last updated 2025-04-06; status last verified 2025-03.
- Results first posted 2024-08-28.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed, prospective, non-randomized, single-group feasibility study sponsored by the University of California, Los Angeles. It concerns adjustment of current or frequency settings in people with epilepsy and previously implanted FDA-approved VNS devices, with the stated goal of evaluating cardioprotective effects. The study is marked completed, with dates of 2020-12-01 and 2021-07-07 recorded for start and primary completion.
Enrollment is listed as 1. The primary outcome is change in seizure frequency or duration assessed through routine seizure history following the 4-week VNS treatment phase to the end of the study. A secondary outcome concerns heart rate and blood pressure responses to upright tilt, deep breathing, the Valsalva maneuver, and a cold pressor test. The participant completed only the first study visit and did not return. The registry lists no analyses and no numerical outcome results in the registry record for interpretation.
The record also lists 0 serious adverse events, 0 other adverse events, and 0 deaths among the recorded at-risk count of 1. These counts are limited and do not establish absence of risk.