Beet the Cold: The Effect of Inorganic Nitrate Supplementation in Individuals With Raynaud's Phenomenon: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beet the Cold: The Effect of Inorganic Nitrate Supplementation in Individuals With Raynaud's Phenomenon (NCT03129178), a randomized na study. The primary outcome is Peripheral Blood Flow.

2. Clinical Question

The motivation described in the record is that dietary nitrate can be converted in the body to nitric oxide, which is involved in blood-vessel relaxation. The trial was intended to examine short- and longer-term beetroot juice supplementation in people with Raynaud's phenomenon, including blood flow and pain, and to inform planning for a definitive trial. Those aims are not themselves findings: without reported outcome estimates, the registry record cannot establish whether the measured blood flow changed with either drink sequence.

3. Trial Design

This was a randomized, triple-masked, placebo-controlled crossover pilot trial. The title identifies the study as a pilot, and the registry lists the model as crossover. Participants were assigned to one of two drink sequences: concentrated beetroot juice followed by nitrate-depleted beetroot juice, or nitrate-depleted beetroot juice followed by concentrated beetroot juice. In a crossover design, participants receive interventions in sequence, so measurements can potentially be compared within the same participant as well as across treatment periods. That general feature does not establish which statistical model was used in this trial.

The intervention descriptions specify a 140ml drink before an experimental visit, then 70ml daily for 2 weeks, followed by another 140ml drink before a later visit. The placebo sequence has the same stated volumes and schedule. The registry record does not provide further details on adherence, exact allocation procedures, or the timing and length of any washout between periods. It also does not explain the masking procedures or identify which groups of people were masked; it reports triple masking only.

Enrollment was 27. The primary-outcome description refers to 20 individuals with Raynaud's phenomenon. The record does not say whether this refers to participants with available measurements, a defined analysis population, or another subset. It reports that the study was completed and lists the study start and primary completion dates as 2017-07-01 and 2018-07-01, respectively. The phase is listed as NA.

The primary outcome was peripheral blood flow measured as CVC. Perceived discomfort, acceptability, recruitment, perceived pain, feasibility, and retention are among the listed secondary outcomes. The record lists eight outcome measures overall, but does not provide numerical results for these outcomes. The design and stated aims can be described from the registry, but the statistical analysis plan, sample-size justification, and any interim analyses 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.

Before assignment: 27 participants were consented.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 20 individuals with raynauds phenomenon. Result reported is Blood flow (CVC), 10 minutes after rewarming for the chronic exposures (Baseline (day 1), visit 2 (day 2), 3 (day 16), 4 (day 23) and 5 (day 36) respectfully).

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 Peripheral Blood Flow, measured over Baseline (day 1), Acute (2 or 23), Chronic (day 16 or 36)..

The primary endpoint is peripheral blood flow, expressed as cutaneous vascular conductance (CVC). The registry defines CVC as skin flux divided by mean arterial pressure (MAP), and gives the unit as flux.mmHg-1. Skin flux is the blood-flow signal in the skin; dividing by MAP expresses that signal relative to arterial pressure. This is the measure the trial used to characterize peripheral blood flow in the study population.

The outcome description states that the reported quantity is blood flow (CVC), 10 minutes after rewarming for the chronic exposures. It names baseline on day 1 and visits 2, 3, 4, and 5 on days 2, 16, 23, and 36, respectively. The separate timeframe field lists baseline (day 1), acute (2 or 23), and chronic (day 16 or 36). The registry does not clarify the relationship between these descriptions, so the timing should be read as recorded rather than interpreted as a more specific schedule.

In general, CVC is useful when the research question concerns blood flow in relation to blood pressure, rather than skin flux in isolation. Repeated measurements can describe how the measure varies over the specified visits and exposure periods. That rationale explains the endpoint's role; it does not tell us whether beetroot juice altered CVC in this trial.

The record identifies the outcome as continuous and gives mean and standard deviation as its summary format. However, it contains no numerical means or standard deviations, no treatment contrast, and no confidence interval for the primary endpoint. Accordingly, the size and precision of any difference in peripheral blood flow are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details available in the registry record are limited. It identifies a continuous primary outcome summarized as a mean with a standard deviation, and it describes a randomized crossover design. It does not report the fitted model, the treatment-effect estimate, its uncertainty, or a hypothesis test. The methods below explain general statistical concepts relevant to this design; they are not claims about methods actually used in this trial.

For a continuous outcome, a mean describes the arithmetic average of observed measurements. A standard deviation describes how spread out individual measurements are around that mean. In general, neither one alone describes the treatment comparison: the interpretation also depends on the estimated contrast between conditions, how that contrast was calculated, and its uncertainty. The registry record names mean and standard deviation as the dispersion format but supplies no primary-outcome values.

In a crossover trial, a participant receives more than one intervention over time. In general, this permits comparisons within a participant, which can reduce the influence of stable characteristics that differ across people. Measurements from the same participant are correlated, however, and should not be treated as though every measurement came from a different person. Analysis methods for crossover data commonly account for repeated observations and may need to consider treatment, period, sequence, and possible carryover. The particular model and handling of these features are not reported in the registry record.

A confidence interval is a range of values compatible with the observed data under a specified statistical procedure and its assumptions. It communicates precision as well as the direction and scale of an estimated effect. A narrow interval generally indicates more precise estimation than a wide interval, while an interval spanning values on either side of no difference can leave the direction uncertain. These are general interpretations; there is no primary-outcome confidence interval reported for this trial.

A p-value, when reported, measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry record reports zero analyses and supplies no primary-outcome p-value. Consequently, statistical significance cannot be assessed from the available entry.

Random allocation is intended, in general, to reduce systematic differences in assigned treatment groups. Masking can reduce some risks of biased behavior or assessment. The record identifies randomization and triple masking, but does not detail allocation concealment, the masking procedures, or who was masked. Those labels alone do not demonstrate that every potential source of bias was prevented.

The primary outcome is measured repeatedly at named visits and exposure periods. General analysis of repeated measurements must distinguish the intervention effect from changes over time, and must account for the association among measurements from the same person. If both sequence and period matter, ignoring them can lead to misleading uncertainty or treatment estimates. The registry does not state whether the outcome was analyzed at every listed visit, whether a single contrast was designated as primary, or how repeated observations were handled.

Dispersion and sample size affect precision. In general, greater variability makes an effect harder to estimate precisely at a fixed sample size, while more observations can improve precision when the design and assumptions are appropriate. This does not mean that a sample-size calculation establishes an effect or guarantees a particular result. The record says that planning illustrations were based on an observed effect and specified general assumptions, but it does not include the calculated values or a trial-specific design justification. It would therefore be inappropriate to infer a target sample size, statistical power, or the adequacy of enrollment from the entry.

For a crossover study, general sample-size planning also depends on within-participant variability and the correlation between repeated measurements, in addition to the size of the effect the study aims to detect. Those design inputs are not reported. The record does not explain whether the enrollment of 27 was based on a formal calculation, feasibility constraints, or another rationale. Nor does it report a justification for the 20 individuals mentioned in the primary-outcome description.

Multiplicity arises when several outcomes, time points, treatment contrasts, or statistical tests are examined. In general, conducting many tests can increase the chance of obtaining at least one apparently unusual result by chance. Prespecified outcome hierarchies or adjustments can address some multiplicity concerns, depending on the scientific question. Eight outcome measures are listed, and several time points are described for the primary endpoint, but the registry record does not say how multiplicity was managed or whether any adjustment was planned.

Missing-data methods are also important when repeated outcomes are collected. In general, the handling of missing measurements can affect both the estimated treatment effect and its uncertainty, especially if missingness relates to participant characteristics or outcomes. The registry does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. The difference between enrollment and the primary-outcome population description cannot by itself establish how much data were missing or why.

Finally, a pilot study is often used to assess procedures and gather information for later research. Feasibility outcomes can include recruitment, retention, acceptability, and adherence, but the registry entry only lists some of these as outcomes; it does not report their numerical results. Without those findings and without the primary-outcome estimate, the statistical record is insufficient to judge either the treatment contrast or the feasibility of a definitive trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including peripheral blood flow as the primary outcome and secondary outcomes concerning discomfort, acceptability, recruitment, pain, feasibility, and retention. Multiple outcome measures and repeated assessment times create potential multiplicity: in general, examining many comparisons can increase the chance of at least one result appearing unusual by chance. The registry record does not report a prespecified testing hierarchy, multiplicity adjustment, or other approach to controlling the interpretation of multiple tests.

The primary endpoint description names several visits and exposure periods, while the timeframe field groups assessments as baseline, acute, and chronic. The record does not clarify which contrast was intended as the single primary comparison, how the multiple time points were incorporated, or whether separate tests were planned for them. It also does not report an analysis plan or primary-outcome results.

The record identifies 27 enrolled participants and refers to 20 individuals in the primary-outcome description. It does not provide participant flow, counts with outcome data by visit or sequence, reasons for non-participation in an analysis, or missing-data methods. Therefore, the relationship between those counts and the analysis population is not reported in the registry record. No conclusion about completeness of follow-up or the handling of missing observations can be drawn.

It is also not reported whether the analysis followed an intention-to-treat principle, used a per-protocol population, or applied another definition. The record lists zero analyses, so it does not describe a statistical model or sensitivity analyses. These omissions limit assessment of how robust any treatment-effect estimate would be, quite apart from the fact that no numerical primary estimate is reported.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the concentrated beetroot juice group with 26 at risk and 0 affected. For nitrate-depleted beetroot juice, it reports 26 at risk and 0 affected. Deaths are reported as 0 in both groups. Other adverse events are reported for 3 of 26 at risk in the concentrated beetroot juice group and 2 of 26 at risk in the nitrate-depleted beetroot juice group.

These are the registry's recorded counts. The record does not name the other adverse events, describe their severity or timing, or explain whether the counts refer to participants with at least one event or to event episodes. It also does not report additional information about exposure duration or the collection and classification procedures for adverse events. The two at-risk counts should therefore be read as recorded for each group, not as a basis for inferring details about the crossover periods or unique individuals.

Zero reported serious events and deaths do not establish that no such events could occur, and the small pilot record cannot resolve rare risks. Conversely, the non-serious event counts do not show that the drinks caused those events. These figures describe the safety information recorded in the registry; they do not replace a fuller account of event types, timing, and attribution.

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

The registry record establishes that a randomized, triple-masked crossover pilot was conducted in people with Raynaud's phenomenon, with concentrated beetroot juice compared with nitrate-depleted beetroot juice. It identifies CVC as the primary measure of peripheral blood flow and describes repeated measurements across the study visits. It also lists outcomes related to discomfort, pain, acceptability, recruitment, feasibility, and retention.

What the record does not establish is whether the active drink changed peripheral blood flow, by how much, or with what precision. Numerical CVC results, a treatment contrast, a confidence interval, and a primary-outcome test are not reported in the registry record. The same limitation applies to the listed secondary outcomes: their names appear, but their numerical findings do not. Thus, the trial entry cannot establish benefit, lack of benefit, equivalence, or absence of an effect.

The stated aim included informing a definitive trial. In general, a pilot can help assess whether procedures are workable and can provide preliminary estimates for planning. However, the registry does not report recruitment rates, retention results, adherence, outcome variability, or a numerical sample-size illustration. The trial's stated purpose should not be mistaken for evidence that those planning aims were met.

The study's crossover design offers the potential for within-person comparisons, but its implications depend on implementation and analysis. The registry does not report the analysis model, treatment-period handling, missing-data approach, or washout details. These gaps prevent a complete appraisal of how the intended comparison was estimated.

The safety record lists no serious adverse events or deaths in either group and gives counts for other adverse events. It does not identify event types or provide context sufficient to attribute them to either drink. Taken together, the registry supplies a useful outline of the research question, design, endpoint, and recorded adverse-event counts, but not the outcome evidence needed to judge the treatment comparison.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly described research question and a reportable treatment-effect result. The registry identifies a randomized crossover structure, a masked placebo comparison, a primary blood-flow measure, and a set of secondary outcomes. Those details help readers understand what investigators intended to study. They do not substitute for the estimates and uncertainty needed to evaluate the observed comparison.

The crossover design makes it especially important to know how repeated measurements were analyzed. In general, comparisons within the same participant can be efficient, but the analysis must account for dependence between measurements and consider the order and timing of treatments. Without the model, contrast, and handling of periods, readers cannot determine how the trial translated its design into an estimate.

The record also illustrates why enrollment and analysis populations need to be distinguished. It reports enrollment of 27 and describes the primary outcome as involving 20 individuals, without explaining the relationship. A transparent account of participant flow and measurement availability would help readers judge the scope of the evidence and the possible impact of missing observations.

Finally, pilot aims are valuable only when the associated feasibility and planning findings are reported clearly. Recruitment, retention, acceptability, and outcome variability can inform later study design, but the registry entry does not provide numerical findings for these measures or the primary endpoint. The statistical lesson is not about the direction of a treatment effect; the record does not report one. Rather, it shows why outcome definitions, participant accounting, analysis methods, estimates, and their precision all matter for interpreting clinical research.

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 interpreting this trial entry is that it contains no numerical primary-outcome results. Although peripheral blood flow is defined as CVC and its measurement schedule is described, no means, standard deviations, treatment contrast, confidence interval, or test result appear in the registry record. The listed secondary outcomes also have no numerical findings.

Participant accounting is incomplete. Enrollment is 27, while the primary-outcome description refers to 20 individuals. The record does not explain this difference, provide a flow of participants through the crossover sequences, or say how many had measurements at each visit. Without that information, it is not possible to characterize the analysis population or assess the possible effects of missing observations.

Several design and analysis details are not reported: the crossover washout arrangements, the allocation procedure beyond randomized assignment, masking procedures beyond the triple-masked label, the statistical model, and handling of treatment period, sequence, and repeated measurements. The record also does not report whether an intention-to-treat population was used, how missing data were handled, whether sensitivity analyses were performed, or how multiple outcomes and time points were addressed.

The timing descriptions are not fully aligned: the timeframe field refers to acute and chronic assessments, while the outcome description names specific visit days and indicates measurement after rewarming for chronic exposures. The record does not resolve how those descriptions map onto each other. It also does not report numerical adherence, recruitment, retention, or acceptability findings, despite listing related outcomes and describing the study as a pilot.

Finally, the safety information is limited to group-level counts, without event terms or further context. These limitations reflect the information absent from the registry record; they do not establish that the trial itself did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Beet the Cold: The Effect of Inorganic Nitrate Supplementation in Individuals With Raynaud's Phenomenon — NCT03129178.
• Registry record last updated 2020-02-10; status last verified 2019-09.
• Results first posted 2020-02-10.
• 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 NCT03129178, a completed randomized, triple-masked, placebo-controlled crossover pilot trial sponsored by the University of Portsmouth. It enrolled 27 participants and compared sequences of concentrated beetroot juice and nitrate-depleted beetroot juice in individuals with Raynaud's phenomenon.

The primary outcome was peripheral blood flow measured as CVC, defined as skin flux divided by MAP. The record refers to 20 individuals in the primary-outcome description and names repeated assessment visits, but does not explain the relationship between that population and enrollment. Perceived discomfort, acceptability, recruitment, pain, feasibility, and retention are among the listed secondary outcomes.

The registry does not report numerical primary or secondary outcome results, a treatment-effect estimate, a confidence interval, or the statistical analysis used. It records zero serious adverse events and deaths in both groups, with other adverse events reported in each group. The trial's statistical findings and precision therefore cannot be assessed from the registry record.