Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA) (NCT01198509), a randomized na study. The primary outcome is Alteration of Microbiota, Alteration of T Cell Function/Activation.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel study sponsored by NYU Langone Health. Its status is completed. The study began in 2010-01, and primary completion was recorded as 2013-01. Enrollment was 178. The phase is listed as NA, which is not a drug-development phase designation in this record.

The primary outcome concerned changes in oral and intestinal microbiota and T-cell function or activation. The registry says these measures were assessed at baseline and at 1, 2, 3, 4, and 5 months after baseline, with a timeframe of 6 months. It describes three RA groups for the primary outcome: doxycycline, vancomycin, and no treatment. The group sizes stated for that outcome were 4, 10, and 19 participants, respectively.

The intervention descriptions specify doxycycline at 100 mg twice a day for 2 months and vancomycin at 250 mg four times a day for 2 weeks. The no-treatment group is described as a comparison group. The broader group description also includes PsA and healthy participants, who were intended to contribute baseline microbiota comparisons. The registry does not give further details about how participants in the broader comparison group were assigned or followed.

Although randomization is recorded, details of sequence generation, concealment, and implementation are not reported in the registry record. The specific masking procedure and which people were masked are also not reported in the registry record. These omissions limit how fully the conduct of randomization and masking can be assessed from the record alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary outcome only evaluated in first three groups of RA patients: 4 randomized to treatment with doxycycline; 10 randomized to treatment with vancomycin; 19 randomized to no treatment.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Alteration of Microbiota, Alteration of T Cell Function/Activation, measured over 6 months.

The primary outcome counts participants who experienced changes in oral or intestinal microbiota, T-cell function, or T-cell activation. The registry describes microbiota change as a change in the relative abundance of microorganisms at the genus and species levels, assessed using high-throughput 16S rDNA sequencing. T-cell function or activation was assessed through the percentage of inhibition of regulatory T cells, measured by interferon gamma levels in in-vitro assays.

These measures address the study’s stated biological question: whether the antibiotic groups differed from one another or from the no-treatment group in microbiota and T-cell outcomes. In general, measuring microbial composition can characterize which microorganisms are relatively more or less abundant; a change in abundance is not, by itself, evidence that a change caused a clinical outcome. Similarly, a laboratory measure of T-cell activity describes an assay result and is distinct from a clinical measure of arthritis symptoms.

The registry gives the primary-outcome timeframe as 6 months and describes assessments from baseline through month 5. It does not report a numerical definition or threshold for deciding which participants counted as having experienced a change. Numerical primary-outcome findings are not reported in the registry record, so the magnitude and direction of any group differences cannot be described from these details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, single-masked, and parallel. In general, random allocation is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee that groups will be balanced in a small study. A parallel design assigns participants to groups that receive different study conditions rather than having each participant receive every condition. The record does not report the randomization procedure, allocation concealment, or masking details beyond the single-masked designation.

What does the primary outcome count?

The primary outcome is expressed as a number of participants who experienced changes in microbiota or T-cell function or activation. The record describes two different types of measurement contributing to this outcome: relative abundance of microorganisms, and an in-vitro measure related to regulatory T-cell inhibition. These are biological measures, not direct clinical outcome measures. The record does not report the threshold or rule used to convert each measure into a participant-level change. Nor does it report how multiple types of change were combined, if they were combined, to determine the participant count.

The outcome description refers to repeated assessments at baseline and at 1, 2, 3, 4, and 5 months. Repeated measurements can describe how a measure changes over time, but they also require a plan for handling measurements that are missing or collected at different times. The statistical approach for these repeated assessments is not reported in the registry record. The registry also lists a 6-month timeframe; the relationship between this timeframe and the stated assessment visits is not further explained.

How should group comparisons be read?

The primary outcome description names three RA groups: doxycycline, vancomycin, and no treatment. The registry does not state which pairwise or overall comparisons were prespecified, what statistical test was used, or whether estimates were adjusted for other variables. Those details are not reported in the registry record. Without a reported estimate and its uncertainty, the group sizes alone do not show whether one group had more or fewer participants with changes.

In general, a confidence interval describes a range of values compatible with the data under the assumptions of the statistical method. Its width conveys precision: wider intervals indicate less precise estimates. A p-value, when reported, measures how unusual data at least as inconsistent with a specified null hypothesis would be under that hypothesis and the model. It is not the probability that the null hypothesis is true, and it does not measure the importance of an effect. No primary-outcome confidence intervals or p-values are reported in the registry record.

What does the analysis count tell the reader?

The registry lists 0 analyses. The record also gives a primary outcome based on participant counts and a secondary outcome of mean change in DAS28 from baseline to 6 months. The posted information does not include numerical analysis results for either endpoint. Consequently, there is no reported estimated effect, standard error, confidence interval, or hypothesis-test result to interpret for these outcomes. A study’s completion status and a recorded outcome definition do not substitute for an analysis result.

General statistical context: for count outcomes, the analysis should account for the scale and distribution of the observations. If data are modeled as counts, over-dispersion can matter when variability is greater than a model assumes; ignoring it can make uncertainty estimates too small. That general concern cannot be evaluated for this study because the outcome counts and model are not reported in the registry record. The endpoint is described as participants who experienced changes, but the analysis method is not specified.

How do the sample-size illustrations differ from the trial design?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participant requirements per arm for non-time-to-event outcomes, with the effect to detect set as a stated fraction of the observed effect. These are planning illustrations based on an observed effect, not the trial’s original design calculations and not observed power. The registry record does not report the trial’s own sample-size justification. Because numerical primary-outcome results are not reported in the registry record, the effect underlying any illustration cannot be assessed from the record alone. The stated sample-size assumptions do not establish that the study was designed or powered according to those assumptions.

In general, a sample-size calculation is conditional on its assumptions about the target effect, variability, allocation, and statistical method. A planning calculation is not a retrospective measure of whether a study had adequate power, and it does not change what the collected data show. No conclusion about precision or detectable effects should be drawn from a planning illustration without the underlying numerical inputs and outcome estimates.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures: the primary microbiota and T-cell outcome and the secondary outcome of mean change in DAS28 from baseline to 6 months. The primary description includes multiple biological measures and repeated assessments, but the record does not state how many comparisons were planned, which were primary within that outcome, or how the analysis addressed multiplicity. It does not report an adjustment method or a prespecified hierarchy for interpreting multiple tests. These details are not reported in the registry record.

In general, testing many outcomes, time points, or group comparisons can increase the chance of at least one apparently unusual result. A prespecified analysis plan and an appropriate multiplicity strategy can help readers interpret that risk. The absence of a reported strategy does not establish that no strategy was used; it means the record does not document one.

Missing-data methods are not reported in the registry record. The record does not state how missing microbiota samples, unavailable laboratory assays, or incomplete follow-up measurements were handled, nor does it report the number of participants with missing outcome data. The analysis population definitions are also not reported in the registry record. Thus, it is not possible to determine from the record whether analyses followed assignment as randomized, included only participants with complete data, or used another population definition.

The primary outcome was evaluated in the specified RA groups, while the wider registry enrollment includes RA, PsA, and healthy participants. The record does not explain in detail how the broader enrollment relates to the analysis population for the primary or secondary outcome. These reporting gaps make it difficult to assess the effects of missing data, selection into analyses, and multiple comparisons on any potential findings.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 as zero in each of the three displayed groups. The numbers at risk for serious adverse events were 4 in the RA doxycycline group, 10 in the RA vancomycin group, and 163 in the RA, PsA, healthy group. The registry lists one other, non-serious adverse event among 10 participants at risk in the vancomycin group, and zero among 4 at risk in the doxycycline group and 163 at risk in the RA, PsA, healthy group.

These counts describe the adverse-event records in the registry. They do not establish whether an event was caused by an intervention, and the record does not give a description of the non-serious event. The larger comparison group combines RA, PsA, and healthy participants in its label; it should not be read as a single antibiotic-treatment group. The record does not report death counts. It also does not provide further information on event timing, severity within the non-serious category, or duration of safety follow-up. In general, adverse-event counts are interpreted in light of the number of participants observed and the period of observation; those details are not fully described for these counts in the registry record.

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

The registry record supports a clear description of the research question: whether doxycycline or vancomycin treatment was associated with changes in oral and intestinal microbiota and T-cell function or activation in the RA groups. It also describes a no-treatment comparison and baseline microbiota comparisons involving PsA and healthy participants. These features make the study relevant to investigating biological associations between antibiotic exposure and the specified laboratory measures.

The record does not report numerical results for the primary outcome or for the secondary DAS28 outcome. As a result, it does not show the number of participants with biological changes by group, the magnitude or direction of differences, or the precision of those differences. It cannot establish from the posted results whether treatment groups differed on the measured outcomes. Nor can an association between microbiota changes and clinical changes be assessed from the registry entries alone.

In general, a change in a laboratory measure is not automatically evidence of a change in symptoms, function, or disease course. The primary endpoint concerns microbiota and T-cell measures, while DAS28 is listed as a separate secondary outcome. Interpreting a relationship between those kinds of outcomes would require the numerical results and relevant analysis details, which are not reported in the registry record.

The recorded safety counts are limited to zero serious events in the displayed groups and one other event in the vancomycin group. These counts should be read as descriptive records, not as proof that an intervention caused or prevented an event. The small primary-outcome groups and the lack of detailed safety information further limit interpretation. Overall, the registry record documents the study question and methods, but not the numerical evidence needed to characterize primary or secondary outcome effects.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are important when biological outcomes, multiple groups, and repeated measurements appear together. The primary outcome combines microbiota and T-cell measures, while assessments were described at several times after baseline. Clear definitions of what counts as a participant-level change and how repeated observations are analyzed are essential to interpreting such an endpoint. Those analysis details are not reported in the registry record.

The primary-outcome groups were small and unequal: 4 participants in the doxycycline group, 10 in the vancomycin group, and 19 in the no-treatment group. In general, small groups can yield estimates with substantial uncertainty, particularly when outcomes are counts. This makes transparent reporting of event counts, effect estimates, and uncertainty especially useful. The registry does not provide numerical primary-outcome estimates or confidence intervals.

The record also separates a biological primary outcome from a clinical secondary outcome, mean change in DAS28 from baseline to 6 months. That distinction matters: laboratory and clinical outcomes answer different questions, and evidence about one does not automatically answer the other. Numerical results for the secondary outcome are not reported in the registry record.

Finally, a completed study record can identify what investigators intended to measure without documenting the results needed for statistical interpretation. For this trial, the registry describes the randomized parallel design, antibiotic regimens, outcome definitions, and adverse-event counts, while leaving the primary and secondary numerical analyses unreported. That contrast illustrates why readers need both a protocol-level description and complete outcome reporting to evaluate estimates, uncertainty, and the scope of conclusions.

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 for interpreting this study from the registry record is the absence of numerical primary-outcome findings. There are no reported group counts for participants experiencing microbiota or T-cell changes, and no effect estimates or measures of uncertainty. Numerical secondary-outcome findings for mean change in DAS28 are also not reported in the registry record. The record lists 0 analyses.

The primary-outcome groups are limited in size, with 4 participants assigned to doxycycline, 10 to vancomycin, and 19 to no treatment. The record does not report whether all participants contributed data at each assessment or how missing samples and measurements were handled. It also does not explain the rule used to classify participants as having experienced a change, or how the different biological measures were combined for reporting.

Several design and analysis details are not reported in the registry record, including the randomization procedure, allocation concealment, specific masking procedures, statistical tests, analysis populations, multiplicity handling, and sample-size justification. The outcome description gives repeated assessment times and a 6-month timeframe, but the relationship between them is not explained. The broader RA, PsA, healthy group is described as a baseline comparison group, while the primary outcome was evaluated only in three RA groups; the record does not fully detail how participants in the broader group relate to outcome analyses.

Safety reporting is also limited: the registry does not describe the one other adverse event in the vancomycin group, provide death counts, or give detailed follow-up information for adverse events. These limitations reflect what is documented in the registry record and do not establish what methods may or may not have been used outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA) — NCT01198509.
• Registry record last updated 2015-01-13; status last verified 2014-12.
• Results first posted 2015-01-13.
• 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

NCT01198509 is a completed, randomized, single-masked, parallel study sponsored by NYU Langone Health, with enrollment of 178. Its stated question concerned oral and intestinal microbiota and T-cell function or activation in RA, with doxycycline, vancomycin, and no-treatment groups. The registry describes doxycycline at 100 mg twice a day for 2 months and vancomycin at 250 mg four times a day for 2 weeks.

The primary outcome was the number of participants experiencing changes in microbiota or T-cell measures, assessed at baseline and at 1, 2, 3, 4, and 5 months, with a 6-month timeframe listed. A secondary outcome was mean change in DAS28 from baseline to 6 months. The primary outcome was evaluated in RA groups of 4, 10, and 19 participants. Numerical primary and secondary outcome findings and analysis details are not reported in the registry record. Safety entries list zero serious adverse events in the displayed groups and one other adverse event in the vancomycin group.