Dietary Salt in Postural Tachycardia Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dietary Salt in Postural Tachycardia Syndrome (NCT01547117), a randomized na study. The primary outcome is Plasma Volume.

2. Clinical Question

3. Trial Design

This was a randomized, unmasked crossover study of dietary sodium in participants with POTS and healthy controls. In a crossover design, the same participant can receive each study condition at different times. The registry record says participants were randomly assigned the order of the two sodium levels. That design allows observations under the two diets to be made in the same people, although interpretation depends on the analysis accounting appropriately for the paired structure.

The high-sodium diet contained 300 mEq sodium/day, while the low-sodium diet contained 10 mEq sodium/day. Procedures were performed at both levels. The primary outcome description specifies measurement of plasma volume on Day 7 of each dietary intervention, after 7 days at that level. The record does not describe a washout period, the full sequence schedule, or whether the analysis adjusted for order or period effects; these details are not reported in the registry record.

The posted plasma-volume summaries are separated by participant group and diet. For healthy controls, the low-sodium summary includes 13 participants and the high-sodium summary includes 12. For participants with POTS, each diet summary includes 14. These are condition-specific counts; they should not automatically be interpreted as independent groups, because participants could contribute data under both diets. One healthy control was excluded from the primary outcome on the high-sodium measurement day because of poor venous access.

The study is listed as completed, with enrollment of 38 and sponsor Vanderbilt University. Its recorded start was 2012-03 and primary completion was 2020-12. The registry record lists no masking. It does not provide further detail on allocation concealment, sequence generation, or the handling of possible period and carryover effects.

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: Healthy Participants: 17 were enrolled and randomized. 1 withdrew due to scheduling. 1 withdrew with migraines in phase 1 (low Na+). 2 withdrew in phase 1 (high Na+): 1 unable to tolerate study diet and another had difficulty cooperating with investigators. Postural Tachycardia Syndrome (POTS): 21 were enrolled and randomized. 6 withdrew before baseline due to age (1), pregnancy (1), prohibited meds (3), and scheduling (1). A 7th patient withdrew during phase 1 (high Na+) due to family illness.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No data analysis for 1 healthy control who had poor venous access on Day 7 of the high sodium diet.

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.

Population: 14 patients with Postural Tachycardia Syndrome (POTS) and 13 Controls underwent testing while on a High Sodium Diet and while on a Low Sodium Diet, administered in a randomly assigned order. Baseline data were collected prior to starting the first dietary phase.

6. Primary Endpoint

The registry lists the primary outcome as Plasma Volume, measured over after 7 days of each dietary sodium level.

The primary endpoint is plasma volume, measured in mL. The outcome description specifies absolute plasma-volume values on Day 7 of the low-sodium and high-sodium dietary interventions. The study used an indicator tracer-dilution technique with the DAXOR Blood Volume Analyzer (BVA)-100 system to determine plasma volume.

Plasma volume is relevant to the study’s stated question because the registry description asks whether a high-sodium diet appropriately expands plasma volume in POTS. The record also describes possible links between sodium intake, plasma-volume regulation, renin-angiotensin-aldosterone activity, renal dopamine, orthostatic tachycardia, and symptoms. Those are the study’s motivating questions, not findings established by the primary endpoint summaries alone.

The results are reported as medians with interquartile ranges. A median describes the middle of the observed values after ordering them. The interquartile range describes the central half of the distribution, bounded by the first and third quartiles; it conveys spread without requiring the values to follow a normal distribution. These summaries describe each diet-and-population group. They do not, by themselves, quantify a paired within-person change or establish whether any observed difference is statistically distinguishable from chance.

The primary endpoint is a physiological measurement, not a direct measure of symptoms or clinical benefit. Symptom and orthostatic outcomes are mentioned in the study’s purpose, but their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the study as randomized, unmasked, and crossover. It posts group-level medians and interquartile ranges for plasma volume, but does not report inferential analysis results. The statistical ideas below are general explanations of how such data and design features are commonly interpreted; they are not claims about analyses conducted in this trial.

What does a median and interquartile range describe?

General: A median is the central observation when measured values are ordered. It is less influenced by unusually high or low observations than an arithmetic mean. The interquartile range spans the central half of the observations, from the first quartile to the third quartile. It helps show how much participant values vary within a group. A median and interquartile range describe the distribution of the observed measurements; they do not estimate the uncertainty of a treatment contrast.

For this endpoint, the registry record labels the summary as a median with interquartile range. The reported summaries are separated by diet and population. Because the design is crossover, participants may contribute a plasma-volume observation under each diet. Separate summaries do not preserve the within-person pairing: they do not show which low-sodium value belongs with which high-sodium value. Consequently, the summaries alone cannot establish the distribution of individual changes.

Why does the crossover design matter?

General: In a crossover study, each participant receives more than one condition, so measurements under different conditions are correlated within a person. A suitable analysis generally accounts for this pairing rather than treating every condition-specific observation as if it came from a different person. The analysis may also need to consider sequence or period effects, and whether a prior condition could influence measurements during a later period. These considerations are design-dependent; the registry record does not state how they were handled in this trial.

Random assignment of diet order can help balance order-related influences across sequences. It does not, by itself, show that the analysis accounted for the crossover structure or rule out carryover. The record says the order was randomized, but details of sequence generation and the statistical model are not reported in the registry record.

What can a confidence interval add?

General: A confidence interval gives a range of values compatible with an estimate under a specified statistical procedure. It conveys uncertainty about an estimated quantity, such as the average or median within-person change between conditions. Its width depends on the amount of information and the variability of the measurements. A confidence interval is not the range containing most individual participants’ measurements, so it should not be confused with an interquartile range.

No confidence interval for the sodium-condition contrast is reported in the registry record. Nor are a test statistic, a p-value, or a model-based estimate of the paired change reported. Therefore, the observed medians and their interquartile ranges cannot be used to infer the precision of the diet comparison.

Why can variability matter?

General: Statistical methods often rely on assumptions about the distribution of measurements or model errors. If variability differs across groups or increases with the mean, methods that assume constant variance may describe uncertainty poorly. Over-dispersion means that observed variability is greater than a model expects; when present, it can make standard errors too small if not accommodated. These are general considerations only. The registry record does not describe a distributional model, an over-dispersion assessment, or a variance adjustment for the plasma-volume outcome.

Reporting medians and interquartile ranges gives readers information about the shape and spread of the observed measurements, but does not reveal which inferential method, if any, was used. The registry record lists no analysis records. It also does not report whether any transformation, covariate adjustment, or sensitivity analysis was performed.

How should planning illustrations be understood?

General: A sample-size planning calculation asks how many participants might be needed to detect a specified effect under stated assumptions. The registry record describes a planning illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It distinguishes participant counts per arm for ordinary outcomes from total event counts for time-to-event outcomes. These assumptions describe an illustration, not the trial’s original design justification.

Any such planning illustration is not observed power and does not change the evidential strength of the posted results. It is conditional on its assumptions and on the effect used as the planning target. The registry record does not report the trial’s own sample-size justification, and no numerical planning result is stated in the record details. The illustration should therefore not be treated as proof that the study had adequate power or as an observed finding.

For the current primary outcome, a fully interpretable inferential report would ordinarily identify the estimand, explain how repeated measurements were handled, give an effect estimate and its uncertainty, and state the analysis population. Those details are not reported in the registry record. The available medians and ranges remain useful for describing the observed distributions, but cannot answer those inferential questions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and one posted secondary outcome: the magnitude of suppression of plasma renin activity from the low-sodium to high-sodium diets. It records no analyses. Results for the secondary outcome are not reported in the registry record. The study description also identifies questions about aldosterone, orthostatic tachycardia, and symptoms, but corresponding results are not reported.

Multiplicity arises when several outcomes or comparisons are tested. General: The more tests conducted, the greater the chance that at least one result may appear statistically notable by chance if no adjustment or prespecified hierarchy is used. The record does not report a multiplicity strategy, an outcome hierarchy, or which comparisons were prespecified. It is therefore not possible to determine how multiple questions were handled statistically.

For missing primary-outcome data, the record specifically states that one healthy control had poor venous access on Day 7 of the high-sodium diet and was not included in the outcome data for that measurement. The healthy-control summaries contain 13 observations under low sodium and 12 under high sodium. The POTS summaries contain 14 under each diet. These condition-specific counts identify the available measurements but do not explain whether any further missingness occurred, or whether missing values were handled in an analysis.

General: Missing data can affect estimates when the probability of an observation being unavailable is related to the outcome or to participant characteristics. The record gives a reason for the absent high-sodium measurement but does not describe a missing-data model, imputation, or sensitivity analysis. It also does not specify a formal analysis population beyond the note about the healthy control’s missing measurement. The effect of missing data on the contrast is therefore not reported in the registry record.

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 adverse-event record lists no serious adverse events in any of the four diet-and-population groups, and no deaths. It lists no other adverse events among healthy controls in the low-sodium group, or among participants with POTS under either diet. In the healthy-control high-sodium group, one other adverse event is recorded among 13 participants at risk. The event term and its relationship to the diet are not specified in the posted safety information.

These are event counts within the registry’s listed groups, not a statistical comparison of safety between diets. Because the study used a crossover design, participants may appear in more than one diet group; the groups should not be assumed to be independent. The safety denominators also need not match the plasma-volume analysis counts: for example, the high-sodium healthy-control safety group lists 13 at risk, while the primary plasma-volume summary includes 12 participants.

Zero recorded serious events means none are listed in these groups; it does not establish that serious events are impossible or that the diets have equivalent safety. The small study enrollment and the absence of event detail limit what can be inferred from these counts. The registry record does not report an event-comparison analysis or establish that an event was caused by a particular diet.

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

The trial’s posted primary result is a set of descriptive plasma-volume summaries after 7 days on each sodium level. In both participant groups, the median plasma volume is higher under the high-sodium condition than under the low-sodium condition. Those values describe the observed measurements, but do not on their own establish a statistically reliable within-person change.

The crossover design is important to interpretation because the same participant may contribute measurements under both diets. A comparison that uses the pairing can differ from one based only on separate group medians. The registry record does not report an estimate of the paired contrast, a confidence interval, or a p-value. Thus, the precision of the observed pattern and the degree to which it may reflect random variation are not reported.

The summaries also do not establish that POTS participants respond differently from healthy controls. That question requires a formal comparison of the diet-related changes between populations. No such result is reported. Nor do the plasma-volume values establish what happened to plasma renin activity, aldosterone, orthostatic tachycardia, exercise capacity, or symptoms. Although these topics appear in the study description or outcome listings, their results are not reported in the registry record.

General: A statistically significant result, if one were reported, would not by itself establish clinical importance; clinical interpretation depends on the size and relevance of the estimated effect as well as its uncertainty. In this record, neither an inferential estimate nor a clinical interpretation of the plasma-volume contrast is posted. The data should therefore be read as descriptive observations, not as proof of a treatment benefit or absence of benefit.

The study is informative about the measurements collected under the two dietary conditions and the pattern of the reported medians. It leaves the central inferential questions unresolved in the registry record: the size and uncertainty of the within-person contrast, whether the response differs between POTS and healthy controls, and whether the physiological measurements correspond to changes in symptoms or other outcomes.

13. Why This Trial Matters Statistically

This trial illustrates why a study’s design and its posted summary statistics need to be read together. The crossover design means that observations under the two diets can be paired within participants. Yet the reported medians and interquartile ranges are group summaries, not a direct summary of those paired changes. A descriptive pattern can be visible while its inferential precision remains unknown.

It also illustrates the distinction between a study question and an available result. The stated aims include plasma-volume regulation, renin activity, aldosterone, orthostatic tachycardia, and symptoms. The posted primary endpoint addresses plasma volume, but results for the other stated questions are not reported in the registry record. Recognizing that distinction prevents a narrow physiological summary from being treated as evidence about every outcome named in the study rationale.

For biostatistical interpretation, the record highlights the importance of identifying the estimand and analysis method. In a crossover trial, the relevant contrast may be a within-person difference, and readers need to know how pairing, diet order, possible period effects, and missing measurements were handled. The record gives the randomized diet order and identifies one missing high-sodium primary measurement, but does not report an inferential analysis or the approach to those design features.

Finally, planning calculations and observed evidence answer different questions. A planning illustration can describe the sample size associated with assumptions about a target effect and error rates. It cannot substitute for an analysis of the trial’s observed outcomes, and it is not observed power. The record’s descriptive results and missing inferential details make that distinction especially important.

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 main limitation for interpretation is that the registry record reports plasma-volume summaries but no inferential analysis results. There is no posted estimate of the within-person contrast, confidence interval, p-value, or analysis model. As a result, the statistical uncertainty and significance of the descriptive pattern cannot be assessed from the registry record.

The crossover structure raises analysis questions that are not resolved in the record. Although participants were randomly assigned the order of the diets, the record does not describe the sequence-generation method, period adjustment, washout, carryover assessment, or how pairing was incorporated into an analysis. These omissions do not show that such issues were mishandled; they mean the approach is not reported in the registry record.

One healthy control lacked the Day 7 high-sodium plasma-volume measurement because of poor venous access. The record does not give a missing-data method or sensitivity analysis. The condition-specific outcome counts differ for healthy controls, and the record does not report whether any other measurements were unavailable for other outcomes.

The reported summaries concern plasma volume only. Results for the named secondary renin outcome and the other questions about aldosterone, orthostatic tachycardia, and symptoms are not reported in the registry record. The record also does not describe a multiplicity plan or the protocol’s sample-size justification. Finally, the adverse-event listing is limited to group counts and does not identify the other event’s nature or establish causality. These limitations constrain interpretation of efficacy-related and safety-related questions without changing what the posted descriptive measurements show.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dietary Salt in Postural Tachycardia Syndrome — NCT01547117.
• Registry record last updated 2022-02-22; status last verified 2022-01.
• Results first posted 2021-12-08.
• 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.

18. Record Summary

The registry record describes a completed, randomized, unmasked crossover study of dietary sodium in participants with POTS and healthy controls. Enrollment was 38. The low-sodium diet provided 10 mEq sodium/day and the high-sodium diet provided 300 mEq sodium/day; the order was randomized. Plasma volume was measured after 7 days at each diet level and reported as medians with interquartile ranges.

The reported median plasma-volume values are higher under high sodium in both groups. One healthy control had no high-sodium Day 7 measurement because of poor venous access. The registry record lists no serious adverse events or deaths; one other adverse event is listed in the healthy-control high-sodium safety group.

Inferential analyses, confidence intervals, and p-values are not reported in the registry record. Results for the secondary renin outcome and the study’s other stated physiological and symptom questions are also not reported. The available findings are therefore descriptive and do not quantify the uncertainty of a diet contrast.