Combining VNS With PT Interventions for Individuals With PD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combining VNS With PT Interventions for Individuals With PD (NCT05871151), a randomized na study. The primary outcome is Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III.

2. Clinical Question

The comparison concerns the addition of active rather than sham stimulation before exercise, within the study's described treatment groups. Because exercise is included in both groups, the registry description does not define a comparison of exercise with no exercise. Nor does it describe a comparison of stimulation without exercise. The question is therefore about the combined intervention as described, and the record does not establish how any observed change should be attributed to stimulation, exercise, or their combination.

3. Trial Design

The registry lists a randomized, single-masked, parallel study. Random allocation means assignment to the study groups is intended to use a chance-based process; the registry does not describe the sequence-generation or allocation-concealment procedures. In a parallel design, the described groups receive their assigned interventions rather than being described as crossing over between them.

The listed groups are active taVNS plus exercise and sham taVNS plus exercise. The active group is described as receiving 15 minutes of active stimulation before exercise sessions. The sham group is described as receiving 0 mA of current for 15 minutes before exercise sessions. The registry labels masking as single, but does not identify which people involved in the study were masked or explain how masking was maintained.

The enrollment listed in the record is 25, and the study status is completed. The listed dates are a start date of 2023-10-01 and a primary completion date of 2024-05-25. These registry fields describe the study record; they do not establish how many participants contributed to any particular outcome analysis. The record does not report the analyzed population or participant flow by group.

The primary outcome is MDS-UPDRS Part III, measured at baseline, immediately post-treatment after 12 study visits (around 4-6 weeks), and at follow-up 4 weeks after the last treatment. The registry also lists cognitive and executive-function measures as secondary outcomes, including MoCA, DKEFS Color Word Interference Test conditions, DKEFS Verbal Fluency Test, Digit Span Test, Digit Symbol Substitution Test, and Flanker. Although the record lists 16 outcome measures, it reports zero analyses. It does not give numerical outcome results or an account of which comparisons were conducted.

4. Participant Flow and Accounting

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

Before assignment: 44 individuals were screened; 25 attended in-person screening and completed informed consent, and 3 were excluded (cognitive/medical criteria). 22 eligible participants were therefore assigned to study arms.

Overall Study

Reasons for not completing this period:

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: We screened 44 individuals. 25 were consented and enrolled between Oct 2023 and May 2024. The study was completed once recruitment goals were met. Three subjects were excluded after in-person screening. Twenty-two participants were randomized (11 per group). One sham participant withdrew due to an unrelated illness, and one active participant missed the follow-up appointment.

6. Primary Endpoint

The registry lists the primary outcome as Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, measured over Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment).

The primary endpoint is the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III). The registry describes it as a measure of motor symptoms associated with Parkinson disease. Its stated scale ranges from 0 to 132: 0 represents no motor symptoms and 132 represents severe motor symptoms. A higher score is described as a worse outcome, reflecting more severe motor symptoms.

The study plans measurement at baseline, immediately post-treatment after 12 study visits (around 4-6 weeks), and at follow-up 4 weeks after the last treatment. Baseline can describe the starting measurement, while measurements after treatment and at follow-up can describe motor-symptom scores at later points. Comparing measurements over time can be informative about the course of scores during and after the intervention period. However, the registry record does not report the actual scores, changes, or statistical comparisons at these time points.

The registry identifies the outcome as continuous and specifies the mean and standard deviation as its summary measures. In general, the mean describes the average score, and the standard deviation describes how dispersed individual scores are around that average. These summaries alone would not establish whether groups differed, how uncertain a difference was, or whether any difference was attributable to the intervention. Those interpretations require outcome results and a stated analysis, which are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization, masking, outcome summaries, and repeated measurements each address a different part of trial interpretation. The registry identifies some design features, but does not report the statistical analysis used for the outcomes. The explanations below are general statistical context, not a description of unreported procedures.

What does random allocation contribute?

In general, random allocation assigns participants to groups using chance rather than investigator choice. It is intended to reduce systematic differences between groups at the start of a study, including differences that may not have been measured. Randomization does not guarantee that groups will be identical, particularly in a study with limited enrollment, and it does not remove the need to report the group outcomes. The record labels this study randomized, but does not report how the allocation sequence was generated, concealed, or implemented.

What does single masking mean?

Masking is intended to limit the influence of knowledge about assigned treatment on aspects of study conduct or outcome assessment. The registry labels the study single-masked. That label does not identify who was masked, and the record does not explain whether participants, clinicians, assessors, or other study staff knew assignments. The sham group receives 0 mA of current for 15 minutes before exercise, but the registry does not report whether participants or staff could distinguish the sham procedure from active stimulation. The effectiveness of masking therefore cannot be assessed from this description alone.

How should a continuous endpoint be summarized?

The primary outcome is continuous, and the registry specifies mean and standard deviation. In general, the mean is a measure of the centre of a set of scores. The standard deviation describes how much scores vary around that mean. Reporting both can help readers understand the average and the spread of scores, but neither is, by itself, an estimate of the uncertainty in a difference between groups. A confidence interval is a general way to express the range of effect estimates compatible with the data under a statistical model; its width reflects precision. No confidence interval or treatment-effect estimate for this endpoint is reported in the registry record.

Why do the repeated time points matter?

The record specifies baseline, immediately post-treatment, and follow-up measurements. Repeated observations on the same participant are related, rather than being independent measurements. General methods for repeated measurements account for that within-participant relationship. A study might also choose to analyze a particular follow-up time point or a change from baseline. The choice affects the interpretation of the estimated contrast. Here, the registry does not report the analysis method, a single primary comparison, or results at the listed time points. Its note indicates that the primary outcome has multiple time points and was not reduced to a single comparison.

What role does a statistical test play?

In general, a test statistic and p-value assess how compatible the observed data are with a specified null model, given the assumptions of the test. They do not measure the size or clinical importance of an effect, and a p-value alone does not show precision. Effect estimates and confidence intervals are useful for understanding magnitude and uncertainty. The registry record reports no primary-outcome test, p-value, effect estimate, or confidence interval, so none can be interpreted for this comparison.

How should planning illustrations be understood?

Sample-size calculations are planning tools that explore how many participants per arm might be needed under stated assumptions. The registry's planning description refers to an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence of the study's observed treatment effect and not a report of observed power. The record does not report the trial's own design justification or a statistical plan that would establish that the illustration was used to design the study.

Overall, statistical concepts can clarify what information would be useful, but they cannot substitute for the absent outcome analysis. The registry identifies the outcome scale, timing, broad design, and some summary conventions. It does not report the analysis population, model, treatment-effect estimate, uncertainty interval, or hypothesis-test result.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 16 outcome measures and names several secondary cognitive or executive-function assessments, as well as the primary MDS-UPDRS Part III. The primary endpoint is measured at baseline, immediately post-treatment, and follow-up. Considering several outcomes or time points can create multiplicity: in general, the more comparisons examined, the greater the chance of finding an apparently notable result by chance if no adjustment or prespecified hierarchy is used. The registry does not report a multiplicity strategy, a hierarchy among outcomes, or a single primary time-point comparison.

Missing data can also affect interpretation. In general, if outcome availability is related to participants' scores or assigned group, analyses limited to observed measurements may not represent the full randomized groups. The registry does not report missingness by group or time point, reasons for missing measurements, or methods for handling missing data. The listed enrollment does not establish how many participants contributed to the primary outcome at each assessment.

The record does not report analysis populations, such as whether results were analyzed according to randomized assignment or according to treatment received. It lists zero analyses, so no population-specific results or sensitivity analyses can be assessed. These omissions leave uncertainty about which participants and comparisons would underlie any treatment-effect estimate. They should be treated as unreported information, not as evidence that missingness, multiplicity, or analysis-population issues were handled in a particular way.

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.

The adverse-event fields report the number at risk and the number affected for serious and other events in each group. For active taVNS plus exercise, the record lists 10 at risk for serious events and 0 affected; it also lists 10 at risk for other events and 0 affected. For sham taVNS plus exercise, it lists 10 at risk for serious events and 0 affected, and 10 at risk for other events and 0 affected. Deaths are listed as 0 in each group. No top serious-event terms are listed.

These are the registry's posted counts, not an estimate of the chance of an event in other settings. A count of zero affected means that no affected participants are recorded in these fields; it does not demonstrate that an intervention has no risk. The record does not explain event-collection procedures, reporting completeness, event timing, or whether the safety denominators correspond to the full enrollment. The adverse-event counts should also be kept separate from the primary motor-symptom outcome: they do not report MDS-UPDRS Part III results.

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

The record establishes that a completed randomized, single-masked, parallel study was registered to examine active versus sham taVNS before exercise in people with Parkinson disease. It identifies MDS-UPDRS Part III as the primary outcome and describes measurement at baseline, immediately after treatment, and at follow-up. It also gives the scale's direction: higher scores correspond to worse motor symptoms.

It does not establish what happened to motor-symptom scores. There are no reported group summaries, treatment-effect estimates, confidence intervals, or tests for the primary outcome, and the record lists zero analyses. Accordingly, the registry record cannot support a conclusion about whether the groups differed, how large any difference was, or how precisely it was estimated. The absence of results must not be interpreted as evidence of no difference.

The study purpose mentions physical function and quality of life, but the registry information does not give numerical results for those outcomes. The listed secondary measures include cognitive and executive-function assessments; their names alone do not show whether scores changed or differed between groups. Likewise, the safety fields report zero affected participants in the listed event categories, but those counts do not establish the absence of risk.

The intervention contrast is also specific: both group descriptions include exercise, with active or sham stimulation before exercise sessions. The record therefore does not provide evidence about exercise compared with no exercise, or stimulation without exercise. Any interpretation should remain limited to the registered comparison and acknowledge that the outcome analyses and their uncertainty are not reported.

13. Why This Trial Matters Statistically

This study is statistically informative as a registered example of a question involving a combined intervention and repeated outcome measurement. The group descriptions make the comparison explicit: active or sham taVNS before exercise. Keeping that contrast clear matters because the record does not describe a group receiving no exercise or stimulation alone. A result from the described comparison would address the assigned treatment packages, not isolate every component without additional design features or assumptions.

The primary motor-symptom measure is collected at multiple points, from baseline through follow-up. Such a schedule can support questions about scores immediately after treatment and their course later, but the analysis must specify which comparisons are primary and how repeated observations are handled. The registry's note that the primary outcome was not reduced to a single comparison highlights why a clearly reported estimand and analysis are important for interpretation.

The record also illustrates the difference between a completed study and a reported statistical result. Completion status and enrollment describe registry fields, while an estimate with uncertainty is needed to assess the primary comparison. Because the record lists zero analyses, it does not permit readers to judge effect magnitude or precision. The safety counts are available as registry fields, but they are separate from evidence about the primary endpoint.

These features matter to researchers and readers assessing what a trial can answer. Clear outcome reporting, analysis populations, missing-data handling, and multiplicity methods would make the intended comparison more interpretable. Those details and the primary outcome results 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 main limitation for statistical interpretation is that the registry record does not report numerical results or analyses for the primary endpoint. It gives the outcome definition and measurement schedule, but no group means, standard deviations, changes, treatment contrast, confidence interval, or test result. The record also indicates that the primary outcome has multiple time points and was not reduced to a single comparison.

Other analysis details are not reported in the registry record, including the statistical model, the primary estimand, the analysis population, missing-data methods, and any approach to multiplicity across outcomes or time points. The record does not describe the randomization procedure or identify who was masked. These omissions prevent assessment of how the intended design was implemented and how a numerical result would have been produced.

The enrollment listed as 25 does not establish how many participants contributed outcome measurements, nor whether each listed time point was available for all participants. The adverse-event fields list 10 at risk in each group, but the record does not explain their relationship to enrollment or to the outcome-analysis population. The completed status does not, by itself, resolve these reporting gaps.

Finally, the registered contrast includes exercise in both groups. Any interpretation would be about active versus sham stimulation in the context of exercise, not the independent effect of exercise or stimulation alone. Since no primary outcome analysis is reported, even that narrower contrast cannot be quantified from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combining VNS With PT Interventions for Individuals With PD — NCT05871151.
• Registry record last updated 2025-12-17; status last verified 2025-11.
• Results first posted 2025-12-17.
• 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

NCT05871151 is a completed randomized, single-masked, parallel study listed with an enrollment of 25. It compares active taVNS plus exercise with sham taVNS plus exercise in people with Parkinson disease. The active group description specifies 15 minutes of active stimulation before exercise; the sham description specifies 0 mA for 15 minutes before exercise.

The primary outcome is MDS-UPDRS Part III, measured at baseline, immediately post-treatment, and follow-up. Higher scores indicate worse motor symptoms. The record lists secondary cognitive and executive-function measures and 16 outcome measures overall, but reports zero analyses. Numerical primary-outcome results, analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record. The adverse-event fields list zero affected participants for serious and other events in both groups, with deaths listed as 0.