Adrenocorticotropic Hormone Stimulation in Postural Orthostatic Tachycardia Syndrome (POTS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adrenocorticotropic Hormone Stimulation in Postural Orthostatic Tachycardia Syndrome (POTS) (NCT01764711), a non-randomized na study. The primary outcome is Alldosterone Increase in Response to Adrenocorticotropin Hormone (ACTH)..

2. Clinical Question

3. Trial Design

NCT01764711 is a completed study sponsored by Vanderbilt University. Its registry record lists the phase as not applicable, the allocation as nonrandomized, the masking as none, and the model as single group. The listed enrollment is 13. Although the record identifies POTS and control groups, it explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The details of how participants entered the groups are not reported in the registry record.

The intervention is cosyntropin administration. For both named groups, the description says participants sit for 30 minutes before a blood draw, receive a small intravenous dose, and have further blood drawn at 30 minutes and 60 minutes after administration. The study summary places the work in the setting of a low-salt diet and describes comparing volunteers without POTS to those with POTS. The duration and monitoring of the diet, the exact drug dose, and whether all enrolled participants completed each procedure are not reported in the registry record.

The primary outcome is a continuous measure: mean plasma aldosterone, in nanograms/dL, at 30 minutes after ACTH injection. The record lists one outcome measure and no analysis entries. It reports completion status but does not give an outcome estimate, a statistical comparison, or analysis details. The study dates and the rationale for its enrollment target 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.

Overall Study

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 Alldosterone Increase in Response to Adrenocorticotropin Hormone (ACTH)., measured over 30 minutes after injection of ACTH.

The primary endpoint is plasma aldosterone at 30 minutes after ACTH injection, summarized as a mean with standard deviation and expressed in nanograms/dL. ACTH stimulation with cosyntropin is described as a way to assess adrenal responsiveness. The endpoint description states that the study asks whether adrenal responsiveness, as reflected by plasma aldosterone, contributes to the pathophysiology of orthostatic tachycardia.

As a continuous measurement, aldosterone can be described by its average level and the spread of individual measurements around that average. The registry record specifies the mean and standard deviation as the outcome summary, but it does not report either statistic for the groups. It also does not report a numerical estimate of the difference between groups or an uncertainty interval. Thus the endpoint definition indicates what was intended to be measured, not what level was observed or how strongly the groups may have differed.

The additional blood draws at 60 minutes are part of the described procedure, but the named primary endpoint is specifically timed at 30 minutes. The registry record does not identify a separate 60-minute primary outcome or explain how that measurement was intended to be analyzed. The endpoint rationale is a study question, not evidence that aldosterone explains the condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary outcome: mean aldosterone in plasma, measured 30 minutes after ACTH injection and expressed in nanograms/dL. It names standard deviation as the measure of dispersion. It does not provide the observed mean or standard deviation, an estimated group contrast, or any inferential analysis. The concepts below explain how such summaries are generally interpreted; they are not a description of an analysis documented for this study.

What does a mean represent?

General explanation: for a continuous measurement, the mean is an average across the observations included in an analysis. It can be a useful description of the typical measured level, but its interpretation depends on which observations were included and whether the average is an appropriate summary of their distribution. The record does not report the group means or the analysis population behind them. It is therefore not possible to describe the observed center of aldosterone measurements.

What does the standard deviation add?

General explanation: the standard deviation describes how spread out individual measurements are around the mean. A smaller spread indicates that observations are more tightly clustered around the average; a larger spread indicates greater variability. It is not the same as the uncertainty in the mean, and it does not by itself show how precisely a group contrast has been estimated. The registry record names standard deviation as the intended dispersion summary but gives no value for either group.

How would a group contrast be interpreted?

General explanation: a comparison of means would describe the difference between the average measurements in two defined groups. Its interpretation depends on the study design, the participants included, the timing and conduct of measurements, and any adjustment specified in the analysis. In a nonrandomized study, a difference may reflect group differences beyond the condition under study. The record itself cautions that these arms are not a like-for-like control comparison. It does not report a contrast, an adjustment strategy, or an analysis plan, so no adjusted or unadjusted comparison can be attributed to the study record.

What would an uncertainty interval communicate?

General explanation: a confidence interval gives a range of estimates compatible with the data and the assumptions of a statistical procedure, and communicates precision as well as the estimated direction and size. A narrow interval generally indicates more precise estimation than a wide interval. It does not account automatically for bias, confounding, measurement problems, or an inappropriate model. No confidence interval is reported in the registry record. As a result, readers cannot assess the precision of a group mean or a potential contrast from the posted results.

What would a p-value answer?

General explanation: a p-value is calculated under a statistical model and a null hypothesis. It describes how unusual the data, or data more extreme, would be if that model and null hypothesis held. It is not the probability that the null hypothesis is true, and it is not a measure of effect size or clinical importance. The registry record reports zero analyses and no p-value. It is not possible to infer statistical significance or the test that might have been intended.

Why does the nonrandomized design matter?

General explanation: random allocation, when used and properly implemented, aims to make comparison groups similar on average in factors that could affect an outcome. In a nonrandomized comparison, group membership may be related to other characteristics that also relate to the measurement. Statistical adjustment can address measured factors under stated assumptions, but cannot guarantee removal of unmeasured differences. The record does not report covariates or adjustment methods. Its explicit warning that the groups are not a like-for-like control comparison should therefore guide interpretation of any future reported contrast.

Why are the missing results consequential?

The endpoint and sampling schedule tell readers what the investigators intended to measure. Without the endpoint values, the amount of between-person variability, and an analysis, there is no statistical basis in the registry record to judge the observed response or its precision. A completed status does not itself supply a result. The record does not report whether the planned measurements were collected for every participant or whether any protocol or analysis decisions changed.

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("Low Salt Diet POTS", "Low Salt Diet Controls")
n   <- c(8, 5)
m   <- c(52.5, 57.9)
sp  <- c(15.7, 26.4)
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  Low Salt Diet POTS  8  52.500  15.700  39.374  65.626
CARM  Low Salt Diet Controls  5  57.900  26.400  25.120  90.680

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and zero analyses. It does not report a statistical analysis plan, hypotheses beyond the stated endpoint description, or a multiplicity procedure. The number of outcomes entered in the registry does not establish how many comparisons, time points, subgroups, or exploratory questions were examined in practice. Whether any correction for multiple testing was planned or used is not reported in the registry record.

The procedure describes blood draws before and after cosyntropin, including measurements at 30 minutes and 60 minutes after injection. The designated primary endpoint is at 30 minutes. The record does not say whether the 60-minute measurement was a secondary endpoint, whether other analytes were analyzed, or how repeated measurements were handled statistically. It would be inappropriate to assume a particular testing strategy or multiplicity adjustment.

The record lists enrollment of 13 but does not report how many participants contributed an aldosterone measurement at the primary time point. Missing data, reasons for missingness, exclusions, protocol deviations, and methods for handling incomplete observations are not reported in the registry record. It also does not define an intention-to-treat, per-protocol, or other analysis population. The adverse-event risk counts are safety reporting denominators and should not be taken as confirmation of the primary endpoint analysis population.

General explanation: missing measurements can reduce the information available for an analysis, and the consequences depend partly on why values are missing. Different missing-data methods rely on different assumptions; none can be selected or evaluated without information about the missingness and the analysis. Similarly, multiple statistical tests can increase the chance of at least one apparently notable result when all null hypotheses hold. Since the registry record does not describe the analysis or multiplicity strategy, neither issue can be resolved from the posted results.

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 record lists 8 participants at risk in the Low Salt Diet POTS group and 5 in the Low Sodium Diet Controls group. It reports zero participants with serious adverse events and zero deaths in both groups. The counts for other adverse events are also zero in both groups. No serious adverse-event terms are listed.

These are the event counts reported in the registry record, not a complete account of how safety was monitored or how long participants were followed. The follow-up period for adverse events, event definitions, collection procedures, and handling of incomplete safety information are not reported in the registry record. Zero reported events therefore means that none are recorded in these fields; it does not establish that no event occurred outside the reported collection or reporting window.

The risk counts are associated with the safety entries. They should not be treated as evidence that the same number of participants had an evaluable primary aldosterone measurement. The registry record does not report the analysis population for the primary outcome. Nor should the safety counts be interpreted as a comparative estimate of risk: this was a nonrandomized study, and the record cautions that its arms are not a like-for-like control comparison.

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

The record establishes that investigators planned to assess plasma aldosterone after cosyntropin administration in people with POTS and controls in a low-salt-diet setting. It identifies a specific primary measurement time, describes the blood-sampling procedure, and records the study as completed. It also describes a nonrandomized design and warns that the named arms are not a like-for-like control comparison.

The posted results do not include the aldosterone measurements or an analysis. Thus the record does not show the direction or size of any response, whether group measurements differed, or how precisely a difference may have been estimated. It cannot support a conclusion that aldosterone is increased, decreased, or unchanged in POTS after stimulation. The stated scientific aim is not itself a finding.

General explanation: an observed association between group membership and a measurement would not necessarily establish that the condition caused the measurement difference, particularly in a nonrandomized comparison. Interpretation would also depend on the measurement process, participant characteristics, missing observations, and analysis methods. The registry record does not provide these outcome and analysis details.

The recorded zero adverse-event counts describe the registry’s safety entries, not the primary endpoint, and do not answer the physiological question. Likewise, the enrollment figure does not show the number of participants with complete endpoint data or the precision of a result. The most defensible conclusion is that the record documents the study question and procedures but does not report the primary result needed to answer that question.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clearly named endpoint and a reported finding. The registry record specifies a continuous physiological measure, its units, and its timing after stimulation. Those details make the intended measurement understandable. Yet the absence of endpoint values and analyses means that the scientific question remains unanswered by the posted results. A completed study status cannot substitute for estimates and their uncertainty.

The design also highlights why comparisons require context. The record describes POTS and control groups but identifies the study as nonrandomized and cautions that the groups are not a like-for-like comparison. That warning matters because differences in measured aldosterone could reflect factors associated with group membership as well as the condition being studied. Without reported group characteristics, an analysis plan, or an adjustment strategy, readers cannot assess those possibilities.

General statistical lesson: a useful report should make clear who contributed data, how the outcome was summarized, what comparison was estimated, and how uncertainty and missingness were handled. It should distinguish exploratory measurements from prespecified primary outcomes and explain any approach to multiple testing. These details allow readers to judge both precision and the limits of an estimate. The registry record does not report them for this endpoint.

Safety reporting is another distinct statistical component. The recorded event counts are useful as a description of what was entered, but they do not provide the missing physiological result and do not establish comparative safety. Separating endpoint evidence, design constraints, and adverse-event reporting prevents one kind of information from being mistaken for another.

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 central limitation of the registry record is that it does not report the primary aldosterone measurements or any analysis. There are no group summaries, dispersion values, effect estimates, uncertainty intervals, or test results. Although one outcome measure is listed, the record lists zero analyses. The primary question therefore cannot be answered quantitatively from the posted results.

The study is described as nonrandomized, and the record cautions that the POTS and control arms are not a like-for-like comparison. This limits causal interpretation of any potential difference. Group characteristics, recruitment details, eligibility criteria, and factors that might distinguish the groups are not reported in the registry record. Nor are adjustment methods or an analysis plan reported.

The registry lists enrollment of 13, but does not report the number with evaluable measurements at the primary time point. Missing data, exclusions, protocol deviations, analysis populations, and reasons for incomplete measurements are not reported. The record describes sampling at both 30 minutes and 60 minutes after injection, but does not explain how the later measurement was analyzed or whether it was secondary.

Further procedural details that would inform interpretation, including the exact cosyntropin dose and the duration of the low-salt diet, are not reported in the registry record. Safety-event follow-up and collection methods are also not reported. The recorded zero event counts should consequently be read as registry entries, not as proof of complete ascertainment. These omissions constrain interpretation independently of the study’s stated physiological rationale.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adrenocorticotropic Hormone Stimulation in Postural Orthostatic Tachycardia Syndrome (POTS) — NCT01764711.
• Registry record last updated 2022-03-31; status last verified 2022-03.
• Results first posted 2022-03-31.
• 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

NCT01764711 is a completed, nonrandomized study sponsored by Vanderbilt University, with listed enrollment of 13. It concerns ACTH stimulation in POTS and control participants in a low-salt-diet setting. The described procedure includes intravenous cosyntropin and blood sampling before and after injection.

The primary endpoint is mean plasma aldosterone in nanograms/dL at 30 minutes after ACTH injection, with standard deviation specified as the dispersion measure. The registry record lists one outcome measure and zero analyses, and does not report endpoint results. It cautions that the named groups are not a like-for-like control comparison.

The adverse-event entries report zero serious events, zero other events, and zero deaths in each group. These counts do not supply the missing primary outcome or establish complete safety ascertainment. Overall, the record documents the intended question and procedures but does not provide a numerical result with which to assess the aldosterone response.