Treating Bacterial Overgrowth in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treating Bacterial Overgrowth in Parkinson's Disease (NCT02470780), a randomized phase 2, phase 3 study. The primary outcome is Change in "Off" Time as Measured by Patient Diary.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-masked trial with a sequential model and lists both phase 2 and phase 3. The interventions were rifaximin and placebo. The study title and summary place the question in Parkinson’s disease with small intestinal bacterial overgrowth; the summary specifically describes previously SIBO-positive participants. The record marks the study completed.

Enrollment is reported as 4. The safety information separately lists 4 participants at risk in the rifaximin group and 2 in the placebo group. These figures do not align with the enrollment figure, and the reason for the difference is not reported in the registry record. They should not be combined or treated as a reconciled account of the randomized population. The record does not report how many participants were randomized, treated, or included in the primary outcome analysis.

The start is listed as 2015-12 and primary completion as 2017-08. The arm descriptions name three-month and six-month follow-up but contain no further description. The primary outcome timeframe specifies measurements from baseline to 1 month and 3 months, and a new baseline at 3 months to 4 months and 6 months. The outcome description also states that participants in the group in question completed the study at 3 months after rifaximin treatment and were not assessed at 4 and 6 months. The registry record does not explain how this follow-up structure relates to the named arms or groups.

The record lists two outcome measures and zero analyses. It does not provide the randomization details, a protocol, or a statistical analysis plan. Consequently, the trial’s intended analysis population, allocation implementation, and the relationship between the sequential model and follow-up groups are not reported in the registry 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.

Phase 1

Phase 2

Analysis population for the primary outcome, as defined in the registry: Participants in this group completed the study at 3 months after treatment with rifaximin. They were not assessed at 4 and 6 months.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in "Off" Time as Measured by Patient Diary, measured over baseline to 1 month and 3 months; new baseline at 3 months to 4 months and 6 months.

The primary outcome is change in off time, measured in hours using a patient diary. The registry definition describes off time as the period when levodopa has ceased to be effective and Parkinsonian symptoms reemerge. In general, a diary-based endpoint can capture symptom timing as experienced and recorded across daily life, rather than relying only on a single assessment visit. Its usefulness depends on consistent diary completion, clear definitions, and a prespecified way to summarize observations; those implementation details are not reported in the registry record.

The stated measurement schedule includes change from baseline to 1 month and 3 months, then a new baseline at 3 months with follow-up to 4 months and 6 months. The record also says participants in the reported group completed the study at 3 months after treatment with rifaximin and were not assessed at 4 and 6 months. Thus the planned endpoint spans several time comparisons, but the registry record does not report estimates for any of them, their standard deviations, or inferential results.

In general, change from baseline aims to describe how an outcome differs from a participant’s starting measurement. The interpretation depends on which baseline and follow-up are paired and on how repeated measurements are handled. Here, the later time window explicitly uses a new baseline at 3 months, but the registry record does not report the calculation or analysis method. It also does not report whether diary data were summarized per participant before group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record characterizes the primary outcome as a continuous measure summarized by a mean and standard deviation. The outcome is change in diary-recorded off time, in hours. No primary outcome analysis is posted. The concepts below are general statistical explanations and should not be taken as a description of methods actually used in this study.

What does a mean describe?

In general, a mean is an average that condenses a set of measurements into one value. For a continuous outcome such as hours of off time, the mean can describe the average observed value or average change in a group. A mean alone does not show whether individual participants had similar or very different changes. Nor does a mean change alone establish a difference between randomized groups. For a treatment comparison, the estimated contrast between groups and its uncertainty are important. No such estimates are reported in the registry record.

What does a standard deviation describe?

In general, a standard deviation describes how dispersed individual observations are around their mean. It reflects variation among the observed values, not the precision of the group mean itself. Precision also depends on the number of observations and the analysis. A small standard deviation does not automatically imply a precise treatment comparison, and a large standard deviation does not alone determine whether a comparison is informative. The registry identifies standard deviation as the dispersion measure for the continuous outcome but does not report any values.

How should repeated measurements be understood?

The outcome schedule names several follow-up comparisons, including a new baseline at 3 months for later follow-up. In general, repeated measurements from the same participant are related rather than independent. An analysis needs to account for that relationship if it models multiple time points together. Another possible approach is to define separate changes at specified time points, but the intended approach must be stated in advance and interpreted in light of multiplicity and missing observations. The registry record does not report whether repeated measures were analyzed jointly, separately, or by another method.

The record says participants in one described group completed study follow-up at 3 months and were not assessed at 4 and 6 months. This is important for interpreting the later scheduled windows: the later observations are not reported for that group. The reason, the number of participants affected, and any method for handling absent follow-up are not reported in the registry record. In general, missing observations can affect both the number of measurements available and the validity of an estimate, especially if the likelihood of missingness is related to outcomes or participant characteristics.

Why does the comparison need an uncertainty measure?

In general, a confidence interval combines an effect estimate with information about its uncertainty. A narrow interval indicates greater precision under the chosen analysis assumptions; a wide interval indicates less precision. It can show which effect sizes are compatible with the data, while a point estimate alone cannot. No confidence interval or other uncertainty measure for the primary comparison is reported.

In general, a hypothesis test evaluates data against a null hypothesis under specified assumptions. A p-value is not the probability that a treatment works, and it does not measure the size of an effect. It should be read alongside an effect estimate and interval. The record reports no test, p-value, or statistical model for the primary outcome, so none can be interpreted for this trial.

What does multiplicity mean for this outcome?

In general, multiple outcomes, time points, or comparisons create multiple opportunities to obtain a statistically notable result by chance. A prespecified primary comparison and a stated multiplicity strategy help readers understand how such testing was addressed. Several time windows are listed for off time, but the registry record does not identify a single primary time-point contrast, report a testing hierarchy, or describe an adjustment strategy. The number of listed outcome measures is 2, but the record does not explain how they relate to the multiplicity plan.

The registry record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and distinguishes participant-per-arm planning for non-time-to-event outcomes. These are planning assumptions, not a report of the trial’s original design justification. No sample-size justification for this trial is reported in the registry record. Planning illustrations are not observed power and cannot replace the missing outcome estimates or analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome schedule includes several measurement windows: baseline to 1 month and 3 months, and a new baseline at 3 months to 4 months and 6 months. The registry record does not identify which contrast was the principal inferential comparison or how the multiple time points were handled. It also does not report a multiplicity adjustment, a hierarchy of tests, or whether any analyses were designated exploratory. In general, when multiple comparisons are examined, a prespecified strategy helps distinguish confirmatory inference from exploratory findings. Without that information, the intended control of false-positive findings is not reported in the registry record.

The outcome description states that participants in the group described completed at 3 months and were not assessed at 4 and 6 months. The record does not state why those later assessments were absent, how many participants were affected, or whether later observations were available for other groups. It does not report a missing-data method, assumptions about missingness, imputation, sensitivity analyses, or a participant flow by outcome and time point. Thus the later measurement windows cannot be evaluated for completeness or analyzed from the registry record.

The record does not define an intention-to-treat, per-protocol, treated, or other analysis population. It does not say how participants with incomplete diaries or missing visits were handled. Overall enrollment is 4, whereas the safety denominators are 4 in the rifaximin group and 2 in the placebo group; the reason for this difference is not reported in the registry record. The number of participants contributing to the primary outcome at each time point is also not reported. These omissions limit assessment of both bias and precision.

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 posted safety figures list 4 participants at risk in the rifaximin group and 2 in the placebo group. Serious adverse events affected 0 in each group. Other adverse events affected 0 in each group, and deaths were 0 in each group. No serious adverse event terms are listed.

These counts are descriptive. With the small denominators shown, zero recorded events does not establish that an event cannot occur, nor does it provide a precise estimate of comparative safety. The registry record does not report a statistical comparison of adverse events, event definitions, exposure duration, or detailed safety follow-up. It also does not explain why the at-risk counts differ from the overall enrollment figure of 4. The figures should therefore be read as the recorded counts in each listed group, not as a complete resolution of the participant population or as evidence of equivalence between treatments.

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

The record establishes that a randomized, double-masked study was conducted to investigate rifaximin versus placebo in the context of small intestinal bacterial overgrowth in Parkinson’s disease. It specifies diary-measured change in off time as the primary outcome and defines off time in relation to levodopa no longer being effective and Parkinsonian symptoms reemerging. These details describe the research question and the intended clinical measure.

The record does not report numerical results for the primary outcome or any analysis. Consequently, it does not show whether the observed mean change favored either group, how large any between-group difference was, or how precisely such a difference was estimated. No confidence interval or p-value is reported. The lack of posted results is not evidence that the groups had the same outcomes, and it cannot be interpreted as evidence of benefit or lack of benefit.

The follow-up schedule includes multiple time points, while the outcome description says participants in the specified group were not assessed at 4 and 6 months. The registry record does not explain the missing later assessments or state how they were addressed analytically. It also does not clarify the discrepancy between enrollment of 4 and the safety denominators of 4 and 2. These reporting gaps limit interpretation of the study population and the reach of any potential findings.

In general, a trial’s conclusions depend on its estimates, uncertainty, analysis population, and the completeness and quality of outcome measurement. Here, those elements are not available for the primary efficacy question. The defensible reading is therefore limited: the study design and intended endpoint are documented, but the registry record does not provide the outcome evidence needed to characterize the comparative effect.

13. Why This Trial Matters Statistically

This study raises several statistical issues that are important in small clinical trials. The registry reports enrollment of 4, while safety denominators are 4 for rifaximin and 2 for placebo. The reason for the discrepancy is not reported in the registry record. Clarifying the participant flow matters because readers need to know who was randomized, who received treatment, and who contributed data to each outcome. Those denominators also shape how much precision an estimate can achieve.

The primary measure is continuous and is recorded over several follow-up periods. The specified later periods begin from a new baseline at 3 months, while participants in the described group were not assessed at 4 and 6 months. This makes the definition of the estimand—the treatment contrast and time point the analysis is intended to represent—particularly important. The registry record does not report that estimand or an approach to repeated measurements and absent follow-up.

In general, a small dataset can produce highly uncertain estimates even when the analysis is conducted correctly. This makes transparent reporting of group summaries, effect estimates, uncertainty intervals, and participant counts especially useful. None of the primary outcome estimates is reported. The registry’s sample-size planning assumptions are not a substitute for those results and are not the trial’s documented design justification.

The safety counts also illustrate why denominators and event descriptions need to be read together. No serious or other adverse events and no deaths are listed, but the record gives no detailed exposure or event-level account. Overall, the statistical importance of the record lies as much in its reporting gaps as in its design: readers can identify the question and outcome, but cannot quantify the comparative outcome or its precision.

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 principal limitation for interpretation is that numerical primary outcome results are not reported in the registry record. Group means, standard deviations, between-group estimates, confidence intervals, and p-values are absent, and the record lists zero analyses. The endpoint can be described, but its observed direction, magnitude, and precision cannot be assessed.

The study’s participant accounting is unclear. Enrollment is reported as 4, while safety information lists 4 at risk for rifaximin and 2 for placebo. The reason is not reported in the registry record. Counts randomized, treated, completing follow-up, and included in each outcome analysis are also not reported. This prevents an assessment of the outcome-specific denominators and the extent of attrition.

The primary outcome has multiple stated time windows, and later follow-up uses a new baseline at 3 months. The record also says the group described was not assessed at 4 and 6 months. It does not report the reason for the absent assessments, the handling of missing diary data, or the analysis model. The primary contrast and any multiplicity strategy are not reported in the registry record.

Other trial details that would support interpretation—including the dose and schedule, eligibility criteria, allocation procedure, masking implementation, sample-size justification, and analysis population—are not reported in the registry record. The arm descriptions do not add detail about follow-up. These limitations mean the record can support a description of the study question and selected design features, but not a quantitative judgment of efficacy, precision, or the robustness of the analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treating Bacterial Overgrowth in Parkinson's Disease — NCT02470780.
• Registry record last updated 2024-03-01; status last verified 2024-02.
• Results first posted 2024-03-01.
• 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 record describes a completed randomized, double-masked study of rifaximin versus placebo in Parkinson’s disease and small intestinal bacterial overgrowth. It lists phase 2 and phase 3, a sequential model, enrollment of 4, and the primary outcome of diary-measured change in off time. The recorded timeframe includes baseline to 1 month and 3 months, followed by a new baseline at 3 months and follow-up to 4 months and 6 months.

No primary outcome analyses or numerical efficacy results are reported. The safety counts list no serious adverse events, other adverse events, or deaths in either group, with at-risk denominators of 4 for rifaximin and 2 for placebo. The reason those denominators differ from reported enrollment is not reported in the registry record. Key details on missing data, analysis populations, multiplicity, and the statistical model are also not reported.