Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid (NCT03648996), a randomized phase 2 study. The primary outcome is Carotid Femoral Pulse Wave Velocity (cfPWV).

2. Clinical Question

3. Trial Design

The registry classifies NCT03648996 as a completed, randomized, triple-masked, parallel study. It lists enrollment of 34 and a phase 2 designation. The study title and description focus on sex-related differences in arterial stiffness and the possible role of uric acid among people with type 2 diabetes. The record lists type 2 diabetes and hyperuricemia as conditions.

The study description outlines three separate interventions. In the first, men and post-menopausal women with type 2 diabetes were to receive allopurinol or placebo for 6 months. In the second, participants were to follow a low-fructose diet while maintaining baseline weight. In the third, participants were to follow a low-fructose diet with a stated energy reduction and weight reduction. These descriptions set out the intended interventions; they do not establish that every planned arm contributed to the posted primary outcome results.

The posted primary outcome data contain results for Allopurinol, Placebo, and Low-fructose Diet, Hypocaloric. The respective reported sample sizes are 6, 4, and 15. No primary outcome result for the isocaloric low-fructose diet appears in the record. The available data therefore do not constitute a complete report of every intervention described in the study summary.

The primary outcome was intended to be assessed at baseline and 6 months. The record also lists brachial artery flow-mediated dilation and insulin-stimulated leg blood flow as secondary outcomes. Endothelial function, systemic inflammation, and oxidative stress are mentioned in the study description, but that description does not supply numerical results for these measures. The record lists the study as completed, but does not report a statistical analysis plan, detailed allocation procedures, or the handling of participants who did not contribute endpoint measurements.

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: The current Clinical trials.gov information reflects the number of subjects that were recruited for the clinical trial portion of this study. No subjects were recruited the isocaloric portion of this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Measurement not available for all subjects

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 Carotid Femoral Pulse Wave Velocity (cfPWV), measured over This will be assessed at baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point..

Carotid-femoral pulse wave velocity (cfPWV), reported in m/s, is the primary endpoint. It measures how quickly the pressure wave travels between the carotid and femoral sites. The registry describes calculating transit time between the pressure waves and dividing the distance traveled by the pulse wave by that transit time. It calls cfPWV a gold-standard non-invasive index of arterial stiffness and states that the measurements were to be made by the same blinded technician.

In general, pulse wave velocity is used as an indicator of arterial stiffness because the speed of a pressure wave through the arterial system reflects the properties of the vessel walls. A faster wave is generally associated with stiffer arteries. This makes cfPWV a physiological measurement relevant to the study’s focus on vascular function; it is not itself a direct measurement of a clinical event or of a participant’s overall health.

The registry says cfPWV was to be measured at baseline and 6 months, with the goal of comparing change from baseline with the final time point. The posted primary outcome values are arm-level means with standard deviations, but the record does not identify them as change-from-baseline estimates or provide the paired baseline and final values. Consequently, the available values describe the groups as posted but do not show the amount or uncertainty of change over the study period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies cfPWV as a continuous endpoint summarized by a mean and standard deviation. These summaries describe the center of the observed values and their spread within each reported arm. The mean is the arithmetic average of the measurements included in that arm’s summary. The standard deviation describes how dispersed those measurements are around the mean; it is not a confidence interval and does not directly show how precisely the mean estimates a broader population value.

What does a confidence interval add?

In general, a confidence interval combines an estimate with an indication of its sampling uncertainty under a specified statistical method. A narrow interval indicates greater precision than a wide interval, although the interpretation depends on the model and assumptions used. No confidence intervals are reported for the posted cfPWV means or for between-arm comparisons, so the precision of any treatment contrast cannot be assessed from an interval in the registry record.

What would a treatment comparison require?

The study description frames the primary endpoint as change from baseline to the final measurement. In general, a direct analysis of that question would compare changes between groups or model follow-up values while accounting for baseline values, according to a prespecified analysis plan. Such an analysis would need to define which participants are included, how missing measurements are handled, and what contrast is being estimated. The registry record does not report these analysis details or a numerical change estimate. The posted means should therefore not be treated as though they were adjusted treatment effects.

How should the reported spread be read?

In general, a standard deviation describes variation among individual measurements, whereas the standard error describes uncertainty in an estimated mean. They answer different questions. The registry reports standard deviations, not standard errors. A standard deviation can be large even when an estimate is reasonably precise in a large sample, and can be an unstable guide to the population spread in a small sample. The arm-level counts and standard deviations should be read as summaries of the observed data, not as evidence of statistical significance.

Why can over-dispersion matter?

In general, over-dispersion means that the observed variability is greater than a statistical model assumes. If a model understates variability, its uncertainty estimates may be too small and its tests may be too optimistic. This issue is especially relevant to outcomes whose values are counts, rates, or event totals. cfPWV is a continuous measurement, and the record does not report a model fit or evidence of over-dispersion. The concept is not a claim about this trial’s data; it illustrates why a statistical model’s assumptions need to match the outcome and observed variability.

The registry identifies the study as randomized, triple-masked, and parallel. Randomization is intended, in general, to reduce systematic differences between assigned groups, while masking is intended to limit the influence of knowledge about assignment on care or assessment. These design labels do not replace reporting of the randomization method, concealment procedures, masking roles, or an analysis that respects the assigned groups. The record does not describe those details. It does state that one blinded technician was to make the cfPWV measurements.

No statistical analyses are listed in the posted record. Thus, there is no reported test or model from which to evaluate covariate adjustment, the treatment contrast, or uncertainty. The record does not report a sample-size justification for the trial. General sample-size planning illustrations, when available, are different from trial results: they depend on assumptions about the effect to detect, variability, significance level, and allocation. They are planning exercises, not observed power and not evidence that a study can detect a particular effect.

The record includes an assumption statement for planning illustrations, describing a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. Those details describe a planning approach, not the trial’s own design justification. The registry record does not report a trial-specific target effect or sample-size rationale. Planning calculations cannot repair the absence of an inferential analysis for the posted endpoint data.

More generally, p-values and confidence intervals are complementary rather than interchangeable. A p-value summarizes how incompatible data are with a specified null model under its assumptions; it does not measure the probability that a treatment works or that the null hypothesis is true. An interval communicates a range of estimates compatible with the data and method, and makes precision easier to assess. Neither quantity is available for these posted primary outcome results. The appropriate statistical reading is therefore descriptive and bounded by the information the registry reports.

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("Allopurinol", "Placebo", "Low-fructose Diet, Hypocaloric")
n   <- c(6, 4, 15)
m   <- c(8.71, 7.8, 8.28)
sp  <- c(1.47, 1.04, 1.4)
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  Allopurinol  6  8.710  1.470  7.167  10.253
CARM  Placebo  4  7.800  1.040  6.145  9.455
CARM  Low-fructose Diet, Hypocaloric  15  8.280  1.400  7.505  9.055

11. Multiplicity, Missing Data and Analysis Populations

The study description includes a primary outcome and secondary measures of brachial artery flow-mediated dilation and insulin-stimulated leg blood flow. It also describes separate drug and dietary interventions. Considering multiple outcomes or comparisons can increase the chance of observing a seemingly notable result by chance when many statistical tests are performed. Statistical methods can address this issue by specifying a primary contrast in advance or adjusting for multiple comparisons. The registry record does not report whether multiplicity was addressed, which comparisons were prespecified, or how any adjustment would be made.

No statistical analyses are listed in the record, so there are no reported adjusted or unadjusted inferential results to interpret. The absence of an analysis report also means the record does not state whether there were interim analyses or whether any stopping rules were used. These details are not reported in the registry record.

The primary outcome description explicitly notes that measurement was not available for all subjects. The record does not explain the amount or reasons for missingness, give missing-measurement counts by arm, or describe an imputation or other missing-data method. It also does not state whether the analysis followed an intention-to-treat approach, used an available-measurement population, or applied another analysis-population definition.

In general, missing data can affect both the precision and the interpretation of an estimate. If the chance of a missing measurement is related to the outcome or to treatment assignment, an analysis restricted to measured participants may not represent the originally assigned groups. The registry record does not provide enough information to determine whether missingness could have introduced bias or how sensitive the results are to it. The posted arm summaries should therefore be understood as reported measurements, without assuming a particular analysis population or missing-data procedure.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection/pneumonia (6.2%).

The registry reports serious adverse events by arm, with the number at risk and the number affected. For Allopurinol, 0 of 7 participants at risk were recorded as affected by a serious adverse event; for Placebo, the corresponding figures are 0 of 5; for Low-fructose Diet, Hypocaloric, they are 1 of 16. The record lists 0 deaths in each of these arms. These counts describe the registry’s reported safety data; they do not establish that an intervention caused or prevented an event.

The registry also lists a top serious-event term, “Urinary tract infection/pneumonia,” at 6.2%. The record does not provide enough detail in this entry to attribute that term to a particular intervention or to infer a causal relationship. Serious adverse events are distinct from the separately reported category of other adverse events. The record lists other adverse events affecting 5 of 7 participants in Allopurinol, 4 of 5 in Placebo, and 8 of 16 in Low-fructose Diet, Hypocaloric.

These safety counts should be read in context: the arm sizes reported as at risk are limited, and the registry record does not provide event narratives, exposure-adjusted rates, or a comparative safety analysis. A count of zero in a group is not proof that an event cannot occur, and a count in one group does not show that assignment caused the event. The registry record does not report a formal statistical comparison of adverse-event risk.

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

The posted results establish that the registry contains descriptive cfPWV means and standard deviations for Allopurinol, Placebo, and Low-fructose Diet, Hypocaloric. They also establish that the recorded endpoint sample sizes differ across those arms. This information is useful for describing the measurements that were reported, but it is not a complete account of the study’s stated intervention program or its intended baseline-to-final outcome assessment.

The results do not establish whether cfPWV changed during follow-up. The registry’s endpoint description specifies measurement at baseline and 6 months, but the posted arm-level summaries do not identify a change estimate or provide both time-point values. Without a clearly defined between-group contrast and an uncertainty estimate, the means cannot show whether the observed values represent a meaningful treatment difference or could reflect sampling variation.

The record also does not establish a sex-related difference in response. Although the title and study description emphasize sex and describe men and post-menopausal women, no sex-specific outcome estimates or interaction analysis are reported. It does not establish whether lowering serum uric acid, restricting fructose while maintaining weight, or restricting fructose with an energy reduction changed arterial stiffness. The missing isocaloric diet result further limits interpretation of the planned intervention comparisons.

In general, randomized design can support causal comparisons when the trial’s allocation, outcome collection, analysis populations, missing data, and statistical methods are adequately reported and the analysis compares assigned groups appropriately. The registry labels this study randomized and masked, but those labels alone do not supply the missing comparative analysis. The posted summaries should not be taken as evidence that an intervention does or does not work, and they do not provide a basis for medical decisions.

The central conclusion is about the scope of the evidence in the registry record: descriptive group summaries are available, but inferential results for the primary question are not. Precision, statistical compatibility with no group difference, and the size of any intervention effect remain unquantified in the record.

14. Why This Trial Matters Statistically

This trial is statistically notable because its scientific question involves several linked ideas: arterial stiffness, serum uric acid, dietary fructose, body weight, and sex-related differences. The design description outlines distinct interventions, while the primary endpoint is a continuous physiological measurement collected at baseline and a later time point. To connect those elements to a treatment effect, the analysis needs to make clear which intervention contrast is being estimated and how baseline measurements and incomplete endpoint data are handled.

The posted group means and standard deviations offer a starting description of the cfPWV measurements, but they do not resolve the central statistical questions. Readers need to know whether the outcome represents a final value or a change, how much uncertainty surrounds each estimate, and whether differences between arms are compatible with chance variation. The record does not report those inferential results. This distinction between describing observed values and estimating comparative effects is important in clinical research.

The trial also illustrates how a broad scientific rationale can generate several possible comparisons. Allopurinol and placebo form one stated intervention, while the dietary descriptions distinguish weight-maintaining from weight-reducing approaches. The record does not provide a complete set of primary outcome results across those arms or report how multiple outcomes and comparisons were prioritized. Without that information, readers cannot determine which contrasts were confirmatory or how the analysis accounted for examining multiple questions.

Finally, the note that primary outcome measurements were unavailable for some participants makes transparent reporting of missingness especially important. Counts, reasons, analysis-population definitions, and sensitivity analyses would help readers judge whether the reported summaries represent the intended randomized groups. These are not reported in the registry record. The statistical importance of the study therefore lies both in its physiological question and in the gap between descriptive endpoint data and the comparative analysis needed to answer that question.

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 primary limitation for interpretation is that the registry does not report inferential results for cfPWV. Means and standard deviations are posted for three arms, but there are no confidence intervals, p-values, test statistics, or adjusted between-arm estimates. The outcome description frames the question as change from baseline to 6 months, while the posted results do not identify a change estimate or show the baseline and final values separately.

The primary outcome record states that measurement was not available for all subjects. The number and reasons for missing measurements by arm, the handling of missing data, and the analysis population are not reported. The posted sample sizes are 6 for Allopurinol, 4 for Placebo, and 15 for Low-fructose Diet, Hypocaloric. The registry does not explain how these outcome counts relate to the stated enrollment or to the planned intervention groups.

The study description includes an isocaloric low-fructose intervention, but no primary outcome result for that arm is posted. The registry also does not present sex-specific outcomes, although the study title and description emphasize sex-related differences. It does not report numerical results for the listed secondary outcomes of flow-mediated dilation and insulin-stimulated leg blood flow.

Important design and analysis details are absent. The record does not report the sample-size justification, allocation procedures, a statistical analysis plan, multiplicity handling, interim analyses, or a definition of analysis populations. It also does not explain whether the stated triple masking applied to participants, clinicians, outcome assessors, or other roles. The description that cfPWV measurements were made by the same blinded technician is informative, but does not resolve those broader reporting gaps.

These limitations prevent a complete assessment of the primary comparison, precision, missing-data bias, and generalizability. They do not prove that the study was conducted incorrectly; they delimit what can be concluded from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid — NCT03648996.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2023-07-03.
• 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

NCT03648996 is listed as a completed, randomized, triple-masked, parallel phase 2 study with enrollment of 34. Its stated focus is sex-related differences in arterial stiffness and the role of uric acid in people with type 2 diabetes. The primary outcome is carotid-femoral pulse wave velocity in m/s, intended to be assessed at baseline and 6 months.

The registry describes interventions involving allopurinol, placebo, a low-fructose diet with weight maintenance, and a low-fructose diet with an energy reduction. Posted primary outcome summaries are available for Allopurinol, Placebo, and Low-fructose Diet, Hypocaloric. They report means, standard deviations, and arm-level counts, but no inferential comparison or change-from-baseline estimate.

The record notes that primary outcome measurement was not available for all subjects. It lists two secondary outcomes, but does not post their numerical results. Missing-data handling, analysis populations, multiplicity procedures, and a trial-specific sample-size justification are not reported in the registry record. The available primary outcome information is therefore descriptive rather than a statistical test of the stated treatment question.