Gastrointestinal Symptoms in Postural Orthostatic Tachycardia Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gastrointestinal Symptoms in Postural Orthostatic Tachycardia Syndrome (NCT03263819), a registered phase not stated study. The primary outcome is C-peptide Levels After Oral Glucose Tolerance Test.

2. Clinical Question

The stated aims extend beyond the primary endpoint: the study description names glucose homeostasis, gastrointestinal motility, gastrointestinal and cardiovascular symptoms, and possible differences associated with postganglionic sympathetic fiber neuropathy. These aims provide context for why glucose-stimulated peptide measurements were collected. They do not substitute for outcome estimates. The record lists changes in systemic hemodynamics after oral glucose and during orthostasis as a secondary outcome, but does not report the results for that outcome.

3. Trial Design

The registry record describes an observational comparison involving people with POTS and a group labeled healthy controls, with an oral glucose tolerance test as the listed diagnostic test. Enrollment is 26. The record does not state how participants were allocated, and the listed comparison is not randomized. The arms therefore should not be interpreted as randomly assigned groups, and a difference between them, if reported elsewhere, would not by itself establish that POTS caused the difference.

The group descriptions require particular caution. The POTS arm is described as patients with a POTS diagnosis. The Healthy Controls arm is labeled as controls, but its description refers to patients with POTS who have peripheral neuropathy. This is inconsistent with the label and with the summary’s POTS-versus-healthy-controls framing. The registry record does not clarify whether the description is an error or whether the intended comparator differed from the label.

The study began on 2017-06-20, has a primary completion date of 2020-12-31, and is listed as COMPLETED. These administrative details do not indicate that results were posted. The registry record lists four outcome measures and zero analyses. It does not report a protocol, a statistical analysis plan, a sample-size justification, or the methods used to select participants. The timing or conduct of any interim analyses is not reported in the registry record.

The stated primary outcome is C-peptide levels after oral glucose tolerance testing. The description specifies ingestion of 75 g glucose and a measurement window of 0-120 minutes during intervention. The record does not explain the detailed visit schedule, how many measurements were taken within that window, or how those measurements were summarized for analysis. It also does not establish whether every participant completed every measurement.

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: We enrolled 26 subjects: * 25 subjects completed the study. * 1 subject was excluded from analysis because she was using GLP-1 agonist for weight control

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 C-peptide Levels After Oral Glucose Tolerance Test, measured over 0-120 minutes during intervention.

The primary endpoint is titled C-peptide Levels After Oral Glucose Tolerance Test. It is a continuous measure, expressed in pg/mL, and the registry specifies a mean with standard deviation as the summary format. The stated timeframe is 0-120 minutes during intervention. The outcome description refers to plasma levels and patterns of secretion following ingestion of 75 g glucose. It also mentions GIP, GLP-1 and insulin, alongside C-peptide, while identifying C-peptide as the named primary outcome.

C-peptide is measured in this study in the context of a glucose challenge. In general, measurements taken after a standardized challenge can describe how a biological marker changes over the observation period. A mean summarizes the central level of a continuous measure, while a standard deviation describes the spread of individual measurements around that mean. These summaries answer different questions: the mean concerns the group’s average, and the standard deviation concerns variability among measurements.

The record does not say whether the primary endpoint is a single time point, an average across measurements, a change from a starting value, or another summary of the 0-120-minute profile. It does not report a mean, standard deviation, group contrast, confidence interval or p-value. Consequently, the endpoint’s name and measurement window can be described, but the magnitude and precision of any group difference cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as continuous and specifies a mean with standard deviation. In general, a continuous outcome can take a range of numerical values rather than belonging to a small set of categories. A mean gives a summary of the group’s average value, and a standard deviation describes how dispersed observations are around that average. Neither statistic is reported for the primary endpoint in the registry record, so the observed level and variability cannot be evaluated.

The primary outcome concerns C-peptide measured in pg/mL over 0-120 minutes during the intervention. The description places the measurement after ingestion of 75 g glucose and also names GIP, GLP-1 and insulin. When measurements are taken over time, the analysis must specify what feature of the sequence is being compared: for example, a value at a particular time or a summary across the observation period. That is a general methodological point, not a description of a specified analysis in this study. The registry record does not state how the repeated measurements were reduced or modeled.

Repeated measurements from the same participant are generally related to one another. In general, an analysis that treats all such observations as independent can misrepresent uncertainty, because observations from one person share participant-specific characteristics. Methods for longitudinal or repeated-measures data can account for within-person correlation, but the appropriate choice depends on the design and estimand. The registry record does not report whether repeated-measures methods were used, what covariance structure was assumed, or whether the primary analysis used a single measurement or a profile across time.

Dispersion matters because the same group mean can arise from observations that are tightly clustered or widely spread. Standard deviations help describe that spread, while confidence intervals express uncertainty in an estimate. In general, greater variability or fewer observations can make an estimate less precise. The registry record gives an overall enrollment of 26 but does not report outcome-specific sample sizes, group means, standard deviations or confidence intervals. Precision therefore cannot be assessed from the posted registry information.

The study aims refer to glucose homeostasis, gastrointestinal motility, symptoms and cardiovascular measures, including systemic hemodynamics after oral glucose and during orthostasis. These are distinct outcome domains. A result for one domain would not automatically answer questions about another. The registry lists four outcome measures, but does not provide their numerical results or an analysis plan describing how the multiple measures relate to the primary question.

For a comparison between groups, a statistical analysis could report each group’s estimate and a contrast between them. In general, the contrast should be paired with a measure of uncertainty, such as a confidence interval, so readers can judge the range of plausible values and the precision of the estimate. Adjustment for relevant baseline characteristics can also matter in a nonrandomized comparison, but whether adjustment is appropriate depends on the study question and available data. The registry record does not report a contrast, an adjusted or unadjusted model, covariates, a confidence interval or a p-value.

Allocation is not stated, and the record’s classification indicates that this is not a randomized comparison. Randomization, when used, is intended to balance measured and unmeasured baseline factors on average; it is not reported for this study. In an observational comparison, group differences can reflect the condition of interest, participant selection, other characteristics, or a combination. This general limitation does not imply that any particular bias occurred, but it limits causal interpretation absent further design and analysis details.

The record includes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations use a total number of events. These assumptions describe planning illustrations, not observed power and not necessarily the trial’s original design. The registry record does not report the trial’s own sample-size justification. Since the primary outcome estimates are not reported in the registry record, the observed effect underlying any illustration cannot be assessed from the registry entry.

Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. If a model understates variability, standard errors may be too small and confidence intervals too narrow. The registry record does not report a model or dispersion assessment for this continuous endpoint, so over-dispersion cannot be evaluated as a study-specific issue. This is a general statistical consideration rather than evidence that it affected these data.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("C Peptide Level in POTS Patients", "C Peptide Level in Healthy Controls")
n   <- c(12, 13)
m   <- c(40.6, 23.2)
sp  <- c(9.5, 4.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  C Peptide Level in POTS Patients  12  40.600  9.500  34.564  46.636
CARM  C Peptide Level in Healthy Controls  13  23.200  4.800  20.299  26.101

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, with C-peptide levels after oral glucose tolerance testing named as the primary outcome. It does not report a multiplicity strategy or explain how inference across the outcome measures was handled. In general, testing several outcomes can increase the chance of at least one apparently noteworthy result under a collection of null hypotheses. Possible approaches include designating a primary endpoint in advance, adjusting inference, or treating secondary results as exploratory. The registry record does not say which approach, if any, was used.

Missing-data information is not reported in the registry record. The record does not state how many participants completed the test, how many contributed primary endpoint measurements, whether observations were missing, why they might be missing, or how missing values were handled. These details matter because an analysis based only on participants with complete data can differ from an analysis that accounts for incomplete observations, especially if the reasons for missingness are related to outcomes or participant characteristics. No such pattern can be assessed from the registry entry.

The analysis populations are also not reported in the registry record. It does not state whether results were based on all enrolled participants, a subset who completed the intervention, or another defined population. Although enrollment is 26, enrollment alone does not identify the denominator for any outcome analysis. The registry lists zero analyses, and it does not provide an analysis plan or interim-analysis information. It is therefore not possible to determine from the registry record which analysis population or multiplicity procedure was used, or whether either was prespecified.

12. 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 entries list two groups, POTS and Healthy Controls. For each group, the record gives 13 participants at risk for serious adverse events and 0 affected; it also gives 13 at risk for other adverse events and 0 affected. Deaths are listed as 0 in each group. These are the counts recorded for the respective group entries, not evidence that every possible harm was assessed or that no unrecorded event occurred.

In general, an event count should be read alongside its denominator, the event definition, the observation period and the method used to collect events. The registry record does not provide detail on event-collection procedures, follow-up duration for safety, or the definitions used for the categories. It also does not report a list of serious-event terms; the top serious terms field is empty. Zero affected participants in the entries means that no events are recorded in those counts. It does not establish that the test is risk-free.

The Healthy Controls arm-description discrepancy also applies to interpretation of the group labels: the label says healthy controls, while the description refers to patients with POTS and peripheral neuropathy. The record does not clarify the population represented by that arm. The safety counts should therefore be read as registry-listed group counts without assuming that the comparator description is settled.

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

The record establishes that a completed study was registered with an enrollment of 26 and a primary outcome concerning C-peptide levels after an oral glucose tolerance test. It specifies the measurement unit, summary format and observation window, and its study summary places the measurement within a broader investigation of glucose homeostasis, gastrointestinal motility, symptoms and related physiological measures. Those details describe the scientific question and measurement plan.

The registry record does not report the primary outcome values, group-specific means, standard deviations, a comparison estimate, a confidence interval or a p-value. It therefore cannot show whether C-peptide levels differed between the groups, how large a difference might have been, or how precisely it was estimated. It also does not report the findings for the other outcome measures. A completed status and a stated enrollment do not fill this results gap.

The record’s group descriptions are not fully coherent: the comparator is labeled Healthy Controls but described as patients with POTS who have peripheral neuropathy. This makes the intended population contrast uncertain. In addition, allocation is not stated and the comparison is classified as nonrandomized. Any result from such a comparison, if available, would need to be interpreted in light of possible differences between groups rather than as a randomized treatment effect.

The broad study rationale should not be mistaken for a result. The aims mention possible relationships among POTS, gastrointestinal measures, glucose handling and sympathetic neuropathy, but the registry entry does not establish those relationships. It does not report sufficient numerical data to assess magnitude, precision, consistency across outcomes or causal interpretation. The defensible reading is limited to the registered design and the absence of posted outcome estimates in the registry record.

14. Why This Trial Matters Statistically

This study is statistically interesting because it connects a physiological challenge with several measurement domains. The primary outcome is a continuous C-peptide measure collected after oral glucose, while the stated aims also concern gastrointestinal motility, symptoms, glucose homeostasis and cardiovascular measures. In general, such a design raises questions about how outcomes measured over time are summarized and how uncertainty is handled when multiple related outcomes are considered.

The registry record also illustrates why labels, definitions and analysis details matter. A group called Healthy Controls is described as patients with POTS who have peripheral neuropathy. Without clarification, readers cannot tell from the record whether the intended question is a comparison between POTS and healthy participants or a comparison within POTS by neuropathy status. Those are different questions and call for different interpretations.

Because the comparison is not randomized and allocation is not stated, the design does not support attributing any group contrast to randomized assignment. In general, observed differences in nonrandomized groups may reflect other group characteristics as well as the condition under study. Clear reporting of group composition, outcome estimates, uncertainty, missingness and analysis populations would help readers judge how far a comparison can be interpreted.

The entry reports a completed status, enrollment, outcome descriptions and adverse-event counts, but not numerical efficacy or physiological outcome results. This distinction is important: registration details can establish what was intended to be measured, while estimates and their precision are needed to evaluate what the data show. The absence of those results in the registry record means the statistical evidence for the stated aims cannot be assessed from this entry alone.

15. 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 interpreting this record is that outcome results are not reported in the registry record. The primary C-peptide measure has a named unit, summary format and timeframe, but no group estimates, variability, contrast or uncertainty measure is available. The record likewise does not report results for the secondary outcome or the other listed outcome measures. This prevents assessment of effect magnitude, precision and consistency across outcomes.

Interpretation of the comparator is limited by an internal description mismatch. The arm is titled Healthy Controls, but its description refers to patients with POTS who have peripheral neuropathy. The registry record does not explain which wording reflects the intended group. The summary describes a POTS-versus-healthy-controls objective and also proposes examining POTS participants with and without evidence of postganglionic sympathetic fiber neuropathy; however, the arm text does not allow the actual comparison to be established confidently.

The record does not state allocation, and the comparison is identified as nonrandomized. It does not report baseline characteristics or adjustment methods, so potential differences between groups cannot be evaluated. The registry entry also does not report the primary analysis method, how measurements across the 0-120-minute window were summarized, outcome-specific participant counts, missing-data handling, analysis populations, multiplicity procedures or interim analyses. These omissions limit assessment of both bias and precision.

Enrollment is reported as 26, but the number analyzed for each outcome is not reported in the registry record. The record lists four outcome measures and zero analyses. It does not report the trial’s sample-size justification. The planning assumptions described for sample-size illustrations do not replace information about the original design or the amount of data available for analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gastrointestinal Symptoms in Postural Orthostatic Tachycardia Syndrome — NCT03263819.
• Registry record last updated 2024-07-08; status last verified 2024-07.
• Results first posted 2024-07-08.
• 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.

19. Record Summary

NCT03263819, titled Gastrointestinal Symptoms in Postural Orthostatic Tachycardia Syndrome, is listed as COMPLETED and sponsored by Vanderbilt University Medical Center. The record gives enrollment as 26, a start date of 2017-06-20 and a primary completion date of 2020-12-31. It describes an oral glucose tolerance test involving 75 g glucose and names C-peptide levels after the test as the primary outcome, measured in pg/mL over 0-120 minutes and summarized as a mean with standard deviation.

The stated scientific aims include glucose homeostasis, gastrointestinal motility and related symptoms, with interest in differences associated with postganglionic sympathetic fiber neuropathy. The record lists four outcome measures and zero analyses. It does not report numerical primary or secondary outcome results, analysis methods, missing-data handling or the trial’s sample-size justification. The comparator description is inconsistent: the arm is labeled Healthy Controls but described as patients with POTS who have peripheral neuropathy. Allocation is not stated, and the comparison is not randomized.