Autonomic Neuropathy, GI Motility, and Inflammation in HIV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autonomic Neuropathy, GI Motility, and Inflammation in HIV (NCT02850276), a na early/phase 1 study. The primary outcome is Change in Breath Test.

2. Clinical Question

3. Trial Design

The registry record describes a completed early phase 1, single-group study titled “Autonomic Neuropathy, GI Motility, and Inflammation in HIV.” The listed condition is HIV Disease, and the sponsor is Icahn School of Medicine at Mount Sinai. Enrollment is recorded as 76. The study start is listed as 2015-11, and primary completion as 2018-06-01.

All participants were assigned to the pyridostigmine intervention as described in the record; no separate comparison group is listed. Allocation is recorded as NA, and masking as none. These features matter when interpreting changes over time: a baseline measurement can provide a within-group reference, but without a concurrent control group the study cannot separate treatment-associated change from other influences, including natural fluctuation, changes in care, or measurement variability.

The listed intervention is pyridostigmine, 30mg PO three times a day. The primary outcome compares breath-test results at baseline and week 8. Secondary outcomes listed include mean percent retention of gastric contents on gastric emptying study, changes in sCD14, TNFα, and IL-6 plasma levels, the Composite Autonomic Symptom Score (COMPASS), and the Medical Outcomes Study Questionnaire. The registry identifies 8 outcome measures overall, while the outcome results and their analysis details are not reported in the registry record.

The study is marked completed, but that status does not itself indicate that results were posted or establish what the measurements showed. The record lists 0 analyses. It does not report participant flow, the number contributing data to each endpoint, protocol deviations, or the analysis population. Consequently, enrollment should not be treated as the number analyzed for the breath test or any secondary outcome.

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:

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 Breath Test, measured over baseline and week 8.

The primary endpoint is change in breath test from baseline to week 8. The measure is described as the rise in combined hydrogen and methane during the test, with results expressed in ppm. The endpoint therefore captures a breath-test signal over time, rather than a direct count of bacteria or a direct measure of autonomic nerve activity.

In general, breath tests are used to assess patterns in gases measured after a test procedure. In this study’s stated rationale, altered vagus nerve function could be associated with slower stomach and intestinal movement, which might contribute to bacterial overgrowth and inflammation. The breath-test measure was selected in that context. This rationale describes the biological question; it does not establish that these links occurred in participants.

The registry specifies a median and inter-quartile range as the summary format for the primary outcome. A median describes the middle of an ordered set of measurements, while the inter-quartile range describes the spread across the central part of that distribution. These summaries can be useful when values are not well represented by a mean and standard deviation. The registry record does not report the baseline or week 8 median, the inter-quartile range, or a numerical estimate of change. The direction, magnitude, and precision of the primary endpoint change therefore cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome using a median and inter-quartile range and identifies the comparison as breath-test measurement at baseline and week 8. This tells readers the intended summary format and time points, but it does not provide the numerical summaries or explain the statistical test used. The record does not report an analysis plan, a model, an adjustment strategy, or an estimate with a confidence interval.

What does a median and inter-quartile range convey?

In general, the median is the central value after observations are ordered. It is less affected by unusually high or low measurements than the mean. The inter-quartile range describes the spread of the central portion of the observations. Reporting these summaries can be appropriate when the distribution is skewed or includes extreme values. They describe the observed data; on their own, they do not quantify uncertainty about a treatment effect. For that, an analysis would need to estimate change and its uncertainty using a suitable method.

Because the same participants may be measured at baseline and week 8, an analysis could in general account for the paired nature of repeated measurements. The registry record does not state whether the analysis used paired differences, a repeated-measures model, or another approach. It also does not report whether the primary analysis used all available measurements or only participants with measurements at both times. Those details affect how the estimate should be interpreted and cannot be inferred from the endpoint description.

Why does the single-group design matter?

In general, a before-and-after comparison describes how outcomes change within a group over time. A control group can help distinguish changes associated with the intervention from changes that would have occurred without it. Here, the record identifies a single-group design, allocation as NA, and masking as none. There is no concurrent comparison in the registry description. Thus, even if numerical changes had been reported, the design would limit causal interpretation. This is a design issue, not a judgment about whether a within-group change was measured accurately.

Masking can reduce the influence of expectations on some aspects of trial conduct and outcome assessment. The registry records no masking. It does not provide further information about who knew the treatment assignment or how breath testing was administered and assessed. Those operational details are not reported in the registry record, so their influence cannot be evaluated.

What do the planning assumptions mean?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such sample-size illustrations are hypothetical planning exercises: they describe the group size that would be associated with stated assumptions, not the number actually analyzed and not the probability that this completed study found an effect. The record’s illustrations assume two arms even though the trial is described as single-group, so they should not be read as a reconstruction of this trial’s actual design.

A sample-size calculation depends on assumptions about the effect to detect, variability, allocation, and the chosen statistical framework. If an assumed effect is smaller, detecting it generally requires more information; this is a general statistical principle, not a result from this study. The registry record does not report a sample-size justification from the trial’s own protocol. The planning illustrations are not observed power, and no numerical planning result is stated in the registry record for interpretation.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than is present, its uncertainty estimates can be too small, making results appear more precise than they are. Methods that allow for extra variability may be considered when the data and model call for them. The registry record does not report that over-dispersion was assessed or that any particular model for it was used. This general concept should not be mistaken for a finding about the breath-test data in this study.

For outcomes summarized by a median and inter-quartile range, the shape and spread of the data matter when choosing an analysis and communicating precision. A confidence interval, when reported, gives a range of values compatible with the data under the analysis assumptions; it is not a guarantee that the true value lies in that range. No confidence interval for the primary outcome is reported in the registry record. Without outcome values and uncertainty estimates, neither the size nor the precision of a change can be evaluated.

The registry identifies 0 analyses. It does not state whether results were recalculated from summary statistics, whether any analysis was adjusted, or whether a sponsor analysis was reported. No recalculated estimate or comparison of analyses is available in the registry record. The appropriate reading is therefore descriptive: the record defines the endpoint and its summary format but does not give the statistical results needed to draw an outcome-level conclusion.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary breath-test endpoint. These include mean percent retention of gastric contents on gastric emptying study; changes in sCD14, TNFα, and IL-6 plasma levels; the Composite Autonomic Symptom Score (COMPASS); and the Medical Outcomes Study Questionnaire. It identifies 8 outcome measures overall, but results for those measures are not reported in the registry record.

When a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently notable result can increase. In general, a prespecified multiplicity strategy can address how the analyses are prioritized or how evidence is interpreted across outcomes. The registry record does not report whether multiplicity was addressed, which outcomes were designated secondary in the analysis plan, or whether any hierarchy or adjustment was used. It is therefore not possible to assess how multiple testing was handled.

Missing-data handling is also not reported in the registry record. The record gives enrollment, but not the number contributing data to the primary endpoint or to each secondary outcome. It does not state the amount or pattern of missing measurements, reasons for missingness, or whether any values were imputed. In general, conclusions can depend on how missing observations are handled, especially when availability of follow-up measurements is related to participants’ outcomes or circumstances.

The analysis populations are not described. The record does not say whether analyses included all enrolled participants, only those who received the intervention, or only those with measurements at specified time points. It also does not report exclusions or deviations from the planned analysis. With these details absent, readers cannot determine how broadly an outcome estimate would apply even if one were posted.

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 the pyridostigmine group with 15 at risk for serious adverse events and 0 serious adverse events. For other adverse events, it lists 15 at risk and 5 affected. Deaths are listed as 0. The record does not list any top serious adverse-event terms.

These are counts as recorded in the registry, not a complete description of safety. The record does not report the specific types of the other adverse events, their timing, duration, severity, or whether investigators considered them related to pyridostigmine. It also does not explain the safety analysis period or why the at-risk denominator is 15 while enrollment is recorded as 76. Those details are not reported in the registry record and should not be inferred.

A count of 0 serious adverse events means none were recorded for the listed group and denominator; it does not prove that the risk is absent. A count of 5 other adverse events indicates that events were recorded, but the registry information is insufficient to characterize them. These figures should not be interpreted as a comparison with another treatment because no control group is listed.

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

The registry record establishes that this was a completed early phase 1, single-group study of pyridostigmine in people with HIV. It specifies a primary breath-test endpoint comparing baseline with week 8 and identifies secondary domains involving gastric emptying, inflammatory markers, autonomic symptoms, and quality of life. It also records limited adverse-event counts.

The record does not report the primary breath-test values, the estimated change, or its uncertainty. It therefore does not establish whether the breath-test measure increased, decreased, or remained similar over time. It also does not report results for the secondary outcomes. No conclusion about the observed relationship between autonomic function, gastrointestinal motility, bacterial overgrowth, and inflammation can be drawn from these missing outcome data.

Even if a within-group change were available, the single-group design would not show by itself that pyridostigmine caused the change. Without a concurrent control group, other explanations for change over time cannot be ruled out. This distinction between observed change and causal effect is important in general, particularly for outcomes that may vary over time or be affected by how measurements are collected.

The study’s rationale proposes a possible pathway involving vagus nerve function, gastrointestinal slowing, bacterial overgrowth, and inflammation. A breath-test signal is one measurement within that scientific question; it is not a direct measure of every link in the proposed pathway. The registry’s description of the rationale should not be mistaken for evidence that the pathway was demonstrated.

The safety counts are similarly limited. The record lists no serious adverse events and no deaths for the stated safety denominator, along with 5 other adverse events. It does not describe those events or provide a comparison group. These data are not enough to characterize the full safety profile.

In short, the registry record gives useful information about the study’s design and questions, but it does not provide posted outcome results from which to assess benefit, harm, or the precision of an effect estimate. Absence of results in the record is not evidence that no change occurred.

13. Why This Trial Matters Statistically

This study addresses a question that crosses several areas of clinical measurement: autonomic nerve function, gastrointestinal motility, inflammatory markers, symptoms, and quality of life. Looking at these domains together can help frame hypotheses about how physiological measurements and patient-reported outcomes may relate. The registry’s stated rationale makes clear that the breath-test endpoint was part of a broader exploration rather than a standalone clinical outcome.

Statistically, the study is useful for illustrating the difference between a planned endpoint and a reported result. The registry specifies a baseline-to-week-8 breath-test comparison and a median with inter-quartile range, but it does not post the corresponding values or an uncertainty estimate. An endpoint description alone cannot tell readers whether a change was observed or how precisely it was estimated.

The single-group design also makes causal interpretation an important part of reading the record. A within-group comparison can describe change over time, but it cannot provide the same counterfactual information as a concurrent comparison group. The absence of masking is another design feature to consider when interpreting measurements, though the registry does not describe its practical effect on data collection.

Finally, the record demonstrates why enrollment, analysis denominators, and safety denominators must be distinguished. Enrollment is recorded as 76, whereas the safety figures use 15 at risk for each listed adverse-event category. The record does not explain this difference or state endpoint-specific analysis counts. Those quantities answer different questions and should not be substituted for one another.

The statistical importance of the study therefore lies in the questions it set out to examine and the limits of what its registry record permits readers to conclude. Clear reporting of outcome estimates, uncertainty, analysis populations, and missing-data handling would be needed to evaluate the results in depth.

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 primary limitation for interpretation is that the registry record does not report the primary outcome results. There are no posted baseline or week 8 breath-test summaries, estimate of change, confidence interval, or p-value. The direction, magnitude, and precision of the primary endpoint cannot be determined.

The single-group design has no listed control group, and the record states that masking was none. Thus, the study description does not support a controlled comparison. Any change over time, if measured, could reflect influences other than the intervention. The record does not report enough detail to assess how outcome collection or participant expectations may have affected measurement.

Although enrollment is recorded as 76, the number of participants with primary or secondary outcome data is not reported. The registry record does not state how missing measurements were handled, what analysis population was used, or whether exclusions or protocol deviations occurred. This limits assessment of both precision and potential selection effects.

The registry lists 8 outcome measures overall and several secondary outcomes, but does not report their results or explain whether multiple testing was addressed. It also lists 0 analyses. The analysis methods, model assumptions, adjustment strategy, and any protocol-based sample-size justification are not reported in the registry record.

Safety interpretation is constrained by the reported at-risk denominator of 15 and the absence of detail about the other adverse events. The record does not explain why the safety denominator differs from enrollment, identify the events, or describe their timing or relatedness. These limitations are specific to the information recorded and do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Autonomic Neuropathy, GI Motility, and Inflammation in HIV — NCT02850276.
• Registry record last updated 2019-05-29; status last verified 2019-05.
• Results first posted 2019-05-29.
• 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

NCT02850276 is a completed early phase 1, single-group study sponsored by Icahn School of Medicine at Mount Sinai. It enrolled 76 and evaluated pyridostigmine, listed as 30mg PO three times a day, in people with HIV. Allocation is recorded as NA, and masking as none.

The primary endpoint was change in combined hydrogen and methane breath-test rise from baseline to week 8, summarized by median and inter-quartile range. Secondary outcomes included measures of gastric emptying, inflammatory markers, autonomic symptoms, and quality of life. The record identifies 8 outcome measures and 0 analyses, but does not report the primary or secondary outcome results.

Safety listings include 0 serious adverse events among 15 at risk, 5 other adverse events among 15 at risk, and 0 deaths. Further details about the adverse events and the analysis populations are not reported in the registry record.