Vagal Nerve Stimulation for Gastroparesis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vagal Nerve Stimulation for Gastroparesis (NCT03120325), a non-randomized na study. The primary outcome is Effect of Vagal Nerve Stimulation on Gastroparesis Symptoms as Measures by the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) Questionnaire..

2. Clinical Question

The planned observations covered a baseline period and later assessments during and after the four-week stimulation phase. The trial also described measures of pain, general wellbeing and health, heart rate variability, inflammation and leukocyte infiltration, along with adverse events. These additional measures provide context for the study’s broader interest in gastrointestinal symptoms and possible neuroimmune mechanisms. They do not replace the primary symptom endpoint, and their results are not reported in the registry record.

3. Trial Design

This was a non-randomized, unmasked, parallel-group study of a device intervention. The registry lists three groups: idiopathic gastroparesis, diabetic gastroparesis and functional dyspepsia. The first two groups were described as having delayed gastric emptying; the functional dyspepsia group was described as having normal gastric emptying. Each group description specifies the same vagal nerve stimulation schedule. The groups therefore represent different participant categories, not randomized intervention and control arms.

The registry reports enrollment of 24 and identifies Stanford University as the sponsor. The study began on 2017-03-01, had a primary completion date of 2018-08-24, and is listed as terminated. The reason for termination is not reported in the registry record. The record does not specify the study phase beyond listing it as not applicable.

The brief description outlines six research visits. Screening and baseline visits could take up to eight weeks; the treatment phase was four weeks; and the follow-up or washout phase was described as an additional four weeks. The record notes that total participation could extend to approximately 16 weeks depending on visit timing, while the baseline visit interval could be shorter. These are schedule descriptions, not evidence that every participant completed every visit or the planned treatment period. Completion rates and actual exposure duration are not reported in the registry record.

The study planned endoscopy, breath testing, and blood, stool, urine, heart rate variability and saliva testing. The registry does not describe a randomized allocation process or masking, and explicitly lists the allocation as non-randomized and masking as none. As a result, observed changes over time, if available, would not by themselves separate an intervention effect from time trends, expectation, measurement effects or other changes during participation. The registry record does not report the protocol’s sample-size justification or a detailed statistical analysis plan.

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

Analysis population for the primary outcome, as defined in the registry: Participants who received treatment are included in the analysis.

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 received treatment

6. Primary Endpoint

The registry lists the primary outcome as Effect of Vagal Nerve Stimulation on Gastroparesis Symptoms as Measures by the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) Questionnaire., measured over Baseline (2 weeks prior to initiation), week 4 (7 days), week 8 (7 days).

The primary endpoint was the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD), a symptom questionnaire scored from 0 to 5, with higher scores corresponding to worse symptoms. The registry describes ten items and defines the scale anchors from none to very severe. Daily scores were to be averaged to produce an overall score at each assessment period. The scheduled periods were baseline, described as two weeks before initiation, week 4, and week 8; the latter two periods were each described as seven days.

A daily diary can capture symptom experience repeatedly rather than relying on a single retrospective report. Averaging daily values is intended to represent symptom severity across the specified assessment window. The resulting measure is continuous on the described scale, and the registry identifies the planned summary as a mean with standard deviation. These features make it possible to describe group-level symptom levels and changes over time, if the necessary observations and analyses are reported.

The investigators hypothesized a change of more than 0.75 points. That statement is a planned expectation, not an observed result or a demonstrated threshold of clinical importance. The registry record does not report the actual baseline or follow-up means, the change in score, variability, confidence intervals, or a test of the primary endpoint. It also does not report how missing daily entries were handled when forming an average.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary measure summarized as a mean and standard deviation. It does not report which inferential statistical procedures were used, whether changes were modeled across all assessment periods, or how any adjusted or unadjusted estimates were obtained. The following explains relevant concepts generally; it does not claim that a particular method was used in this study.

What does a mean score represent?

In general, a mean is a way to describe the central level of a continuous measure across participants or observations. For the GCSI-DD, daily questionnaire scores were to be averaged within each assessment period to form an overall score. A group mean can make the overall symptom level easier to describe, but it does not show how scores vary between individuals or whether every participant followed the same pattern. The registry specifies that higher scores correspond to worse symptoms and that the scale ranges from 0 to 5.

A change in a group mean is a summary of the change in the group, not necessarily the change experienced by each person. Individual responses can differ, and a mean can obscure that variation. A clear report would identify the analysis population, the available observations at each assessment, the summary at each time point, and the estimated change with an uncertainty measure. Those numerical results are not reported in the registry record.

What does the standard deviation add?

In general, a standard deviation describes how spread out observations are around their mean. It is not the same as the uncertainty in the estimated mean. A wide spread can indicate that participants’ symptom scores differ substantially, while the precision of a group estimate also depends on how many observations contribute and their structure. The registry says that standard deviations were the planned dispersion measure, but it does not report the observed standard deviations for the primary endpoint.

Repeated daily ratings can also be correlated: measurements from the same participant may be more alike than measurements from different participants. This is a general statistical consideration for diary data. Treating every daily rating as independent can make uncertainty appear too small if the within-participant pattern is ignored. Appropriate analysis may account for repeated observations, but the method used for this study is not reported in the registry record.

How should change over time be interpreted?

The endpoint schedule includes baseline, week 4 and week 8. In general, an analysis of repeated measurements can describe the pattern across time and estimate differences between time points. It may use participant-level information rather than reducing every observation to a single number. The choice of analysis depends on the design, the question, the distribution of scores, and how missing observations arise. The registry record does not report whether the primary analysis compared each follow-up period with baseline, compared time points directly, or used another approach.

A confidence interval is a general way to express uncertainty around an estimated effect. It gives a range of values compatible with the data and the statistical model at a stated confidence level. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the quality of the design and assumptions. No confidence interval for the primary endpoint is reported in the registry record. A p-value, if reported, would address a different question about compatibility with a specified null model and would not by itself describe effect size or clinical importance. No primary-outcome p-value is reported.

Why do allocation and masking matter?

In general, random allocation helps balance measured and unmeasured participant characteristics between intervention groups, while masking can reduce the influence of expectations on care and outcome assessment. This study is listed as non-randomized and unmasked, and the group descriptions assign the same stimulation schedule across clinical categories. Therefore, the groups do not provide an intervention-versus-control contrast. If a change from baseline had been reported, other explanations such as natural symptom fluctuation, concurrent care, expectation, or measurement effects would remain relevant. These are general design considerations, not findings about what happened to participants in this study.

What is over-dispersion, and is it relevant?

Over-dispersion is a general issue for some statistical models used with count or categorical outcomes: the observed variability can exceed what the model assumes. When this occurs, standard errors may be too small unless the model accounts for the extra variability. The primary outcome in this study is described as a continuous score, so over-dispersion is not a defining feature of the stated primary measure. It could be relevant to analyses of some other kinds of outcomes, depending on how they were recorded and modeled. The registry does not report an analysis of this kind or a model assessment.

What can planning calculations establish?

Sample-size calculations are planning tools. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of an observed effect. Such calculations are illustrations under stated assumptions, not observed power and not a record of how this non-randomized study was designed. The assumptions do not establish that the study had a particular planned sample size or that its analysis used a two-arm randomized comparison. The protocol’s sample-size justification is not reported in the registry record.

The registry does not report the effect estimate on which the planning illustration is based, nor does it report the actual primary-outcome estimates needed to assess precision. Any planning figure should therefore be distinguished from the study’s observed results. The analysis method, handling of within-participant correlation, model assumptions, covariate adjustment and treatment of missing data are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes beyond the primary symptom diary, including pain interference, general wellbeing and health, serious or treatment-emergent adverse events, heart rate variability, mucosal inflammation and leukocyte infiltration. Evaluating multiple outcomes can raise a multiplicity question: when many comparisons are made, the chance of at least one apparently unusual result can increase. In general, a prespecified hierarchy or adjustment approach can help define how multiple tests are interpreted. The registry record does not report a multiplicity plan, a hierarchy among secondary outcomes, or whether adjustments were made.

The analysis population for the primary endpoint is described as participants who received treatment. The number who received treatment and the number contributing data at each assessment are not reported in the registry record. The record does not explain whether all randomized or enrolled participants were analyzed, and this was not a randomized study. It also does not report whether participants were excluded from analyses or the reasons for any exclusions.

Missing daily diary entries could affect an average score, particularly if completeness differs by participant or assessment period. In general, missing-data methods rely on assumptions about why values are unavailable; different assumptions can lead to different estimates. The registry describes daily collection over the assessment periods but does not report diary completion, rules for averaging partial diaries, imputation methods, sensitivity analyses or other missing-data procedures. The actual completeness of endoscopy, laboratory and other secondary assessments is also not reported in the registry record.

These omissions limit assessment of selection, completeness and the robustness of any analysis. They do not establish that data were missing or that a particular analytic decision was made; the relevant details are not reported in the registry record.

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 lists serious adverse events separately for each of the three groups. For idiopathic gastroparesis, 0 of 17 participants at risk were recorded as affected by a serious adverse event; for diabetic gastroparesis, 0 of 1; and for functional dyspepsia, 0 of 6. The death count is 0 in each group. These entries describe the registry’s reported counts and denominators, not proof that an event could not occur or that risk is absent.

For other adverse events, the registry records 1 of 17 participants affected in the idiopathic gastroparesis group, 0 of 1 in the diabetic gastroparesis group, and 0 of 6 in the functional dyspepsia group. The serious-adverse-event term list is empty. The record does not provide a description of the other event, its timing, severity, or relationship to the device. The figures should not be interpreted as event rates calculated across follow-up time, because person-time and detailed exposure data are not reported.

These are small group counts in a non-randomized study without a described control group. They cannot establish comparative safety, and zero reported serious events should not be read as evidence of no possible risk. The registry’s safety entries also do not establish whether every participant completed the planned treatment or how adverse events were collected and adjudicated; those details are not reported in the registry record.

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

The record establishes that a study of a handheld vagal nerve stimulation device was conducted in groups described as idiopathic gastroparesis, diabetic gastroparesis and functional dyspepsia. It documents a four-week stimulation schedule, a symptom diary as the primary outcome, a range of additional physiological and patient-reported outcomes, and safety monitoring. It also reports enrollment of 24 and lists the study status as terminated.

It does not establish whether the primary symptom score improved, worsened or remained unchanged. Although the investigators hypothesized a change greater than 0.75 points, the record contains no observed primary-outcome summary or inferential result. The hypothesis is not evidence that the expected change occurred. Without score estimates and uncertainty, readers cannot determine the direction, size or precision of any change from the registry record.

The design also limits causal interpretation. Because allocation was non-randomized, masking was absent and all described groups received stimulation, there is no described control contrast that can isolate the effect of the device. Comparing clinical categories would not answer whether stimulation differs from no stimulation, because those categories differ in diagnosis and gastric emptying status rather than assigned treatment. A pre-treatment and post-treatment comparison, if available, could describe change over time but would not alone rule out alternative explanations.

The safety entries report no serious adverse events in the listed groups and one participant with another adverse event in the idiopathic gastroparesis group. These are descriptive counts from the registry, not a basis for a broad safety conclusion or a comparison with another treatment. The study’s modest enrollment and missing detail on event descriptions and follow-up further limit interpretation.

Accordingly, the record is informative about the study’s intended measurement strategy and reported safety counts, but it is not sufficient to judge the primary symptom outcome or establish a causal treatment effect. Missing analyses should not be interpreted as either positive or negative evidence.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines repeated symptom measurement with a device intervention and several proposed physiological measures. Daily diary data can describe symptom variation across time more richly than a single assessment, while measures such as heart rate variability and inflammatory markers reflect distinct aspects of the study’s proposed mechanism. For statistical interpretation, these outcomes need clear definitions, assessment schedules, analysis populations and uncertainty estimates. The registry describes the planned measures but does not report their results or analysis details.

The study also illustrates the distinction between a clinical group and a comparison group. Idiopathic gastroparesis, diabetic gastroparesis and functional dyspepsia are separate participant categories in the record, but all are described as receiving stimulation. Those categories can help characterize the enrolled population; they do not create a randomized control comparison. This distinction matters whenever readers interpret differences between groups or changes over time.

Another statistical issue is the gap between a hypothesis and an estimate. The registry states that investigators hypothesized a change greater than 0.75 points, but does not report the observed score changes or their precision. A prespecified expectation can guide planning, yet it cannot substitute for reported data. The study’s stated planning assumptions likewise should not be mistaken for the study’s actual design or observed power.

Finally, the record makes clear that the available evidence is incomplete for judging efficacy and detailed safety. It lists the study as terminated and reports 0 analyses, but does not explain the termination or provide the primary outcome analysis. Transparent reporting of participant flow, diary completeness, analysis methods and estimates with uncertainty would be important for assessing how much the data can support. These are general reporting considerations; the missing details are not reported in the registry record.

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 that the registry record does not report any primary-outcome analysis. It gives the GCSI-DD scale, timing and hypothesized change, but no observed score summaries or estimates. Thus, readers cannot assess the magnitude or precision of symptom change. The registry lists 0 analyses, and the reason for termination is not reported in the registry record.

The study was non-randomized and unmasked. The three groups differ by clinical category and gastric emptying description, and each group description specifies vagal nerve stimulation. There is no described untreated or alternative-treatment comparator. Consequently, the design cannot provide the same causal contrast as a randomized controlled comparison, and between-group differences could reflect the groups’ underlying characteristics.

The enrollment was 24, with group sizes reported as 17 for idiopathic gastroparesis, 1 for diabetic gastroparesis and 6 for functional dyspepsia in the safety entries. In particular, the diabetic gastroparesis safety denominator is small, so its safety listing is highly limited as a description of experience. The number of participants treated, number completing follow-up, and amount of primary outcome data available are not reported in the registry record.

The record does not describe the statistical analysis plan, sample-size justification, handling of repeated diary observations, missing data, multiplicity, or covariate adjustment. It also does not report detailed adverse-event terms or the reason for study termination. The planned assessment windows and participation duration are described, but actual visit timing and adherence are not reported. These limitations restrict both interpretation of the planned measurements and assessment of how representative the posted safety counts are of the full study experience.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vagal Nerve Stimulation for Gastroparesis — NCT03120325.
• Registry record last updated 2023-09-13; status last verified 2023-09.
• Results first posted 2023-04-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a non-randomized, unmasked, parallel study of vagal nerve stimulation in 24 participants across idiopathic gastroparesis, diabetic gastroparesis and functional dyspepsia groups. The planned primary outcome was the GCSI-DD symptom score, assessed at baseline, week 4 and week 8. The intervention schedule was four weeks of stimulation, with follow-up or washout described afterward. The study is listed as terminated, with Stanford University as sponsor.

The registry reports no primary-outcome analysis results and lists 0 analyses. It does not report the reason for termination, the number completing treatment, or the statistical analysis and missing-data procedures. Safety listings show no serious adverse events or deaths in the reported groups, and one participant with another adverse event in the idiopathic gastroparesis group. The findings available in the record therefore describe the study plan and reported safety counts, but do not establish the direction or size of symptom change.