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 Does Improving Vagal Tone Increase Mitochondrial Bioenergetics (NCT03931330), a na na study. The primary outcome is To Measure Different Mitochondrial Bioenergetic Markers, Including Basal Respiratory Capacity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03931330 |
| Phase | NA |
| Condition | Functional Gastrointestinal Disorders, Irritable Bowel Syndrome, Dyspepsia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Medical College of Wisconsin |
| Results posted | Yes |
2. Clinical Question
Population
Children with functional gastrointestinal disorders, including functional gastrointestinal disorders, irritable bowel syndrome, dyspepsia, and functional abdominal pain syndrome. The registry describes per-protocol maximal respiration data collected at baseline, after the 4 weeks of therapy, and at long-term follow-up. Further eligibility details and the number contributing data at each visit are not reported in the registry record.
Intervention
Percutaneous neurostimulation, described as a non-invasive percutaneous electrical nerve field stimulator intended to modulate the vagal nerve. The arm description specifies 4 weeks of active therapy. The registry's study summary frames the intervention as auricular neurostimulation.
Comparator
There is no separate comparison group listed. The study is described as single-group, with allocation recorded as NA and masking as none. Measurements at baseline and follow-up provide observations at different times, not a randomized or concurrent control comparison.
Primary question
The primary question is whether mitochondrial bioenergetic markers, including basal respiratory capacity, change after percutaneous neurostimulation. The registry states that higher basal respiratory capacity is better, but does not report the measured values or an estimated change. Heart rate variability and the Functional Disability Inventory are listed as secondary outcomes.
In statistical terms, this record describes a within-group question: whether the measured values differ across the stated assessment times among participants with recorded data. Without a control group, any observed change could not by itself distinguish an intervention-associated change from other explanations, such as natural variation over time. The registry record does not report numerical results with which to assess the direction, size, or precision of any change.
3. Trial Design
The registry lists this as a completed, single-group study sponsored by the Medical College of Wisconsin. Enrollment is 8. The study started on 2019-02-06, and primary completion was 2019-09-24. Phase is recorded as NA. Allocation is recorded as NA, and masking is listed as none. These details describe an open-label study without a separate control group in the registry record.
The intervention is percutaneous neurostimulation, listed as a device. The arm description specifies 4 weeks of active therapy. The registry summary describes evaluation of mitochondrial bioenergetics and inflammation through vagal nerve modulation in children with functional gastrointestinal disorders. It does not report further device settings, treatment adherence, or implementation details.
The primary outcome is described as measurement of different mitochondrial bioenergetic markers, including basal respiratory capacity. The stated timeframe is baseline, follow-up visit 4 at Week 4, and follow-up visit 5 at Week 8 or 12. The registry's population description says per-protocol maximal respiration data were collected at baseline, after completing all 4 weeks of therapy, and at long-term follow-up. It does not clarify the timing of the long-term visit for each participant or report how many participants contributed data at each time.
Heart rate variability and the Functional Disability Inventory are listed as secondary outcomes. The record lists three outcome measures in total, but gives no numerical outcome results and reports zero analyses. Participant flow, withdrawals, protocol deviations, and the analysis population for outcomes other than the described per-protocol maximal respiration data are not reported in the registry record. The single-group design is central to interpreting any change: it allows description of measurements over time, but does not supply a concurrent untreated 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 | Only Active Devise, Open Label |
|---|---|
| STARTED | 8 |
| 4 Weeks of Neuromodulation | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Only Active Devise, Open Label |
|---|---|
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: Per protocol maximal respiration data was collected for patients at baseline, after completing all 4 weeks of NSS Bridge Neurostim therapy and long term follow up post therapy.
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 | Percutaneous Neurostimulation |
|---|---|---|
| Participants analysed | 7 | |
| Age, Categorical: <=18 years | Participants | 7 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 0 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as To Measure Different Mitochondrial Bioenergetic Markers, Including Basal Respiratory Capacity, measured over Baseline, at follow-up visit 4 (Week 4) and at follow up visit 5 (Week 8 or 12).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | pmol/min |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns mitochondrial bioenergetics, with basal respiratory capacity identified as one of the markers. The registry specifies the unit as pmol/min and the summary measure as a mean with standard deviation. The description says blood draws will be tested for mitochondrial function, including basal respiratory capacity, ATP production, and spare respiration, and for changes in protein that can be an indicator for inflammation. It states that a higher basal respiratory capacity is better.
These measurements are intended to describe aspects of cellular energy production and respiratory function. In general, measuring more than one bioenergetic marker can provide a broader picture than relying on a single measurement, but each marker represents a distinct outcome and should be interpreted on its own terms. The registry does not define a composite endpoint or state that the markers are combined into one score.
The endpoint is scheduled for baseline and follow-up assessments, including Week 4 and Week 8 or 12. Repeated measurements can describe whether values change over time among participants with data at multiple visits. They do not, by themselves, establish why a change occurred. The stated unit and summary measure identify how results could be expressed, but the actual means, standard deviations, and changes are not reported in the registry record. The number of participants contributing to the endpoint at each visit is also not reported there.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed study with enrollment of 8, but it does not report numerical results for basal respiratory capacity or the other mitochondrial measures. It also reports zero analyses. Consequently, the posted record does not establish whether measured values increased, decreased, or remained similar over time, nor does it quantify the uncertainty around any change. The endpoint's stated direction—that a higher basal respiratory capacity is better—does not substitute for observed values.
The design is single-group and has no listed comparator. Baseline and follow-up measurements can describe change within participants, if the same participants contribute data at the relevant visits. Such a pattern would not separate intervention effects from time-related change, natural fluctuation, concurrent care, or other influences. Because the registry does not give participant-level visit counts or a numerical analysis, even the completeness and comparability of measurements across visits cannot be assessed from this record.
The registry identifies the primary outcome as a mean with standard deviation in pmol/min. In general, a mean describes the central value of a continuous measurement, while a standard deviation describes variation among observations. Neither one alone conveys the precision of an estimated mean change. A confidence interval would help show the range of values compatible with the data under the analysis assumptions, but no confidence interval is reported in the registry record.
Several related outcomes are named, including basal respiratory capacity, ATP production, spare respiration, protein changes, heart rate variability, and functional disability. The record does not report results for these measures, so it is not possible to judge whether their observed patterns agree or differ. It also does not report an analysis plan, the handling of repeated observations, or whether any tests were adjusted for multiple outcomes and timepoints. Those omissions limit assessment of how the investigators intended to distinguish a clear signal from ordinary variation.
Safety information is also limited to registry counts: the listed active-device group has 7 participants at risk for serious adverse events and 0 affected; for other adverse events, 7 were at risk and 0 affected. Deaths are 0. These counts should be read as recorded event counts, not as proof that the intervention has no risk. The safety record does not supply more detail on the period of observation or event ascertainment.
Overall, the registry record documents the study question, design, measurement schedule, and some safety counts, but not the numerical primary outcome findings. It therefore supports a description of what was planned or recorded, not a conclusion about the magnitude or precision of changes in mitochondrial bioenergetics.
9. Statistical Methods Explained
The registry identifies the primary measurement as continuous and describes it using a mean and standard deviation. In general, a continuous outcome can take a range of numerical values, rather than only belonging to a fixed set of categories. A mean gives a concise description of the observations' central level. A standard deviation describes how spread out those observations are around the mean. These summaries do not show the full distribution, and they do not by themselves answer whether measurements changed from baseline or how precisely a change has been estimated.
What would a within-group change estimate describe?
Because the record lists a single group and assessments at baseline and follow-up, a natural descriptive quantity would be the change in the measured outcome over time among participants with relevant observations. In general, comparing measurements from the same participants can account for the fact that repeated observations on one person are related. The registry does not report a change estimate, its uncertainty, or the method used to analyze repeated measurements. It is therefore not possible to say whether the posted results used a paired comparison, a repeated-measures model, or another method.
Repeated measurements also raise practical questions. A participant may have a baseline measurement but no follow-up measurement, or may contribute to one follow-up but not another. In general, an analysis should make clear which observations contribute to each estimate and how incomplete follow-up is handled. The record does not report visit-specific participant counts, reasons for missing measurements, or a method for dealing with missing data. The phrase per protocol appears in the description of maximal respiration data, but eligibility for that population and its size are not reported.
How should uncertainty be understood?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while an interval compatible with a range of changes may leave the direction or size uncertain. A p-value, when reported, addresses how compatible the data are with a specified null model; it does not measure clinical importance or the probability that a hypothesis is true. No confidence intervals, p-values, or numerical outcome estimates are reported in the registry record, so these measures cannot be interpreted for this study.
Means and standard deviations can be useful summaries, but their interpretation depends on the distribution and on the analysis population. In general, unusual values or skewed data can make a mean less representative of a typical observation. The record does not report distributions, diagnostic checks, transformations, or robust alternatives. Those analysis details are not reported in the registry record and should not be inferred from the endpoint's use of a mean and standard deviation.
What does the planning illustration represent?
The stated sample-size assumptions describe a planning illustration, not the study's own design justification. The illustration uses 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. The registry record does not report a sample-size justification for the enrolled single-group study. Nor does it report numerical planning results in the information available for interpretation.
In general, a planning calculation asks what sample size would be needed under specified assumptions to detect a chosen effect with a chosen level of power. The assumed effect, variability, allocation, significance threshold, and analysis model all affect the answer. A planning illustration based on a fraction of an observed effect is not evidence about the actual study's power, and it is not observed power. Where such an illustration is expressed for a two-arm design, the convention is participants per arm for 80% power; that hypothetical design is distinct from this single-group study. No sample-size illustration can replace a reported treatment estimate and its uncertainty.
Why does the design matter for statistical interpretation?
In general, a control group supplies a concurrent reference for changes that may occur over time even without the intervention. This registry record lists no separate comparator, so a change from baseline would remain a within-group observation. Even a precise estimate of within-group change would not, on its own, isolate an effect attributable to neurostimulation. The record does not report randomization, masking, or a comparative statistical model; allocation is NA and masking is none.
The outcome description includes multiple mitochondrial markers and mentions protein changes, while secondary outcomes include heart rate variability and functional disability. In general, assessing multiple outcomes and timepoints creates multiplicity: the more questions examined, the greater the chance that some apparent patterns arise from random variation. A statistical analysis plan can specify a primary comparison and any adjustment or hierarchy. Such a plan and any multiplicity procedures are not reported in the registry record. No conclusions about statistical significance or consistency across outcomes can be drawn without numerical analyses and details of how they were conducted.
10. Multiplicity, Missing Data and Analysis Populations
The registry names a primary mitochondrial outcome that includes basal respiratory capacity, ATP production, spare respiration, and protein changes related to inflammation. It also lists heart rate variability and the Functional Disability Inventory as secondary outcomes. The primary measurement is scheduled at baseline, follow-up visit 4 at Week 4, and follow-up visit 5 at Week 8 or 12. Considering several markers, outcomes, and assessment times creates multiple opportunities to examine results. In general, multiplicity can make isolated findings harder to interpret because repeated testing increases the chance of apparently notable patterns from random variation.
The registry record does not report a statistical analysis plan, a hierarchy among the individual markers, or any method for controlling multiplicity. It reports zero analyses, so no adjusted or unadjusted findings are available to assess. It is not reported whether the listed markers were intended as separate endpoints, components of an overall evaluation, or exploratory measurements beyond the primary outcome description.
Missing-data information is also absent. The record does not give the number of participants with measurements at each visit, reasons for missing measurements, or a method for handling them. The primary outcome population description refers to per-protocol maximal respiration data, but the definition of that population and its size are not reported in the registry record. It is not reported whether participants with incomplete follow-up were excluded, included for available observations, or handled using another approach.
In general, these details matter because incomplete or selectively available measurements can affect both the estimate and its uncertainty. Without a participant flow, visit-specific denominators, and analysis methods, readers cannot determine how fully the enrolled group contributed to the outcomes. No missingness pattern or remedy should be presumed from the fact that the study is marked completed.
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 |
|---|---|---|---|
| Only Active Device, Open Label | 0 | 7 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Only Active Device, Open Label | 0 of 7 |
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 |
|---|---|
| Only Active Device, Open Label | 0 of 7 |
The registry lists one group, titled Only Active Device, Open Label. For serious adverse events, 7 participants are recorded as at risk and 0 as affected. For other adverse events, 7 are recorded as at risk and 0 as affected. Deaths are recorded as 0, and no top serious-event terms are listed.
These figures describe the registry's recorded counts. They do not indicate that all 8 enrolled participants were included in the safety denominator: the enrollment is 8, while the at-risk counts for both adverse-event categories are 7. The record does not explain this difference or report the duration of safety follow-up, the method of event collection, or whether any participants lacked safety data. Those details are not reported in the registry record.
In general, a zero recorded event count means no events of that category were recorded among the participants counted as at risk; it does not establish that the true event risk is zero. With a small exposed group, rare events may not occur during observation even if they are possible. The registry counts also do not provide a comparator, so they cannot support a comparative safety estimate. These figures should be read alongside the limited event ascertainment details, not as a complete characterization of safety.
12. What the Result Does, and Does Not, Mean
The record documents a study asking whether percutaneous neurostimulation is associated with changes in mitochondrial bioenergetic markers among children with functional gastrointestinal disorders. It identifies basal respiratory capacity as a primary measure and states that higher values are better. It also describes assessments at baseline, Week 4, and Week 8 or 12, with heart rate variability and the Functional Disability Inventory listed as secondary outcomes.
What the record does not provide is the numerical evidence needed to answer the outcome question. Means, standard deviations, changes over time, confidence intervals, and statistical tests are not reported in the registry record. The record reports zero analyses. It is therefore not possible to describe whether the mitochondrial measurements changed, how large any change was, how precise an estimate might be, or whether the different measures showed a consistent pattern.
Even if within-group changes were reported, the design would still matter. This is a single-group study with no listed comparator, so changes over time could not be separated from other time-related influences by a randomized comparison. The open-label design also means masking is listed as none. This does not erase the value of collecting repeated biological measurements, but it limits the claims those measurements alone can support.
The record also does not establish the completeness of the outcome data. Enrollment is 8, while safety denominators are 7, and visit-specific outcome counts are not reported. The per-protocol description does not define eligibility for that analysis population. Without these details, readers cannot assess how much of the enrolled group contributes to the primary endpoint or whether missing data might affect interpretation.
Accordingly, the registry supports a description of the study's question, intervention, planned measurement schedule, and recorded safety counts. It does not support a conclusion about whether mitochondrial bioenergetics changed or whether any observed change would be attributable to the intervention. It also does not provide a basis for clinical advice.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a research question and a reported result. The registry identifies a biological endpoint, a measurement unit, a summary measure, and planned assessment times. Those details help clarify what investigators intended to observe. Yet without numerical outcomes or analyses, the central statistical questions—direction, magnitude, and precision—remain unanswered in the registry record.
The single-group design makes interpretation especially dependent on careful wording. Repeated measurements can reveal patterns within participants, but they do not provide the concurrent counterfactual comparison needed to distinguish intervention-associated change from changes that might have occurred over time for other reasons. This design feature is not a defect in the measurement itself; it defines the scope of inference available from the record.
The record also illustrates why analysis populations and follow-up completeness matter. Enrollment is 8, while 7 participants are listed as at risk in each adverse-event category. The number contributing to each mitochondrial measurement at each visit is not reported. The phrase per protocol identifies a population description, but without its definition or size, the extent of the analyzed data cannot be evaluated.
Finally, the outcome description spans several biological markers and secondary measures. General statistical practice calls for clarity about which outcome is primary, how repeated timepoints are handled, and whether multiple testing is addressed. The registry does not report those analysis details or numerical findings. The most defensible interpretation is therefore limited and transparent: the record describes a completed study and its measurement plan, while leaving its efficacy-related statistical results unreported.
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 important limitation for interpreting this record is the absence of numerical outcome results. Although the registry defines the primary outcome and its measurement schedule, it reports no means, standard deviations, changes, confidence intervals, or tests. It also reports zero analyses. The direction and precision of any change in mitochondrial bioenergetics therefore cannot be assessed.
The single-group design has no separate control group. This limits what a change between baseline and follow-up could establish, because there is no concurrent reference for changes that might occur over time for reasons other than the intervention. Masking is listed as none. The record does not report further design procedures that might clarify how measurements or assessments were conducted.
The enrollment is 8, while the adverse-event risk counts are 7. The reason for this difference is not reported in the registry record. Outcome denominators at baseline and follow-up are also not reported, so the completeness of the primary data cannot be judged. The per-protocol description does not state how the analysis population was defined or how many participants it included.
Other limitations in the record include the absence of a reported statistical analysis plan, missing-data methods, multiplicity procedures, and detailed outcome analyses. The timeframe includes Week 8 or 12 for long-term follow-up, but participant-specific timing is not reported. Device implementation details and safety-event ascertainment details are not reported either. These gaps limit reproducibility and assessment of bias; they should not be filled by assumptions about the protocol.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Does Improving Vagal Tone Increase Mitochondrial Bioenergetics — NCT03931330.
- Registry record last updated 2021-06-21; status last verified 2021-05.
- Results first posted 2021-06-21.
- 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 describes a completed, open-label, single-group study of percutaneous neurostimulation in children with functional gastrointestinal disorders. Enrollment is 8. Active therapy is described as 4 weeks, with mitochondrial measurements scheduled at baseline, Week 4, and Week 8 or 12. The primary outcome includes basal respiratory capacity, ATP production, and spare respiration; higher basal respiratory capacity is stated to be better. Heart rate variability and the Functional Disability Inventory are listed as secondary outcomes.
No numerical outcome results are reported, and the record lists zero analyses. It does not report visit-specific outcome counts, missing-data methods, or a statistical analysis plan. Safety counts list 7 participants at risk and 0 affected for both serious and other adverse events; deaths are 0. These findings describe the registry record and do not provide a comparative estimate of intervention effects.