Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes (NCT05205005), a randomized phase 2, phase 3 study. The primary outcome is Glygocalyx Integrity - Perfused Boundary Region.

2. Clinical Question

The registry record describes a study of dietary supplementation of glycocalyx precursors in participants with type 2 diabetes. The intervention was intended to target the endothelial glycocalyx, a lining of blood vessels. The primary question addressed is narrower: how did the measured perfused boundary region change from baseline to the eight-week assessment in the supplement group compared with placebo?

The posted outcome is a continuous measure, reported as a mean change in micrometers. The summary compares the two groups, rather than asking whether either group changed on its own. This distinction matters: a group’s change from baseline does not by itself show how its change compares with the other group.

The registry’s study rationale proposes that glycocalyx integrity may be relevant to vascular responses to exercise in people with type 2 diabetes. However, the posted primary outcome is glycocalyx integrity, not an exercise-induced vascular adaptation. The secondary outcomes listed concern brachial artery flow mediated dilation, insulin-stimulated leg blood flow, and femoral artery flow mediated dilation. The record does not post analyses for these secondary outcomes.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group trial listed as phase 2 and phase 3. The registry reports enrollment of 24 participants and a completed status. The start date is 2022-05-25, and the primary completion date is 2024-03-31. The sponsor is the VA Office of Research and Development.

Participants were assigned to dietary supplementation of glycocalyx precursors or placebo. The intervention description identifies the supplement as Endocalyx and states that participants took six capsules daily for eight weeks. The placebo description also specifies six capsules daily. The registry record does not explain the allocation sequence, concealment procedures, or which roles were masked; those details are not reported in the registry record.

The primary endpoint is the change in perfused boundary region from baseline to the eight-week assessment. The analysis population for this endpoint is described as participants who completed the full study intervention and had both assessments. Posted group summaries include 10 participants in the supplement arm and 12 in the placebo arm. These counts describe the participants represented in the posted primary outcome results; the record does not explain the difference between these analysis counts and total enrollment.

The record lists three secondary outcomes: brachial artery flow mediated dilation, insulin-stimulated leg blood flow, and femoral artery flow mediated dilation. It lists four outcome measures overall, but no secondary analyses are posted. The original trial sample-size justification, planned analysis model, prespecified significance threshold, interim-analysis plan, and details of the masking procedures are not reported in the registry record. The separate sample-size illustrations on this page are based on the posted effect and are not a description of the trial’s original design.

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: This clinical trial is a proof of concept clinical trial phase that corresponds to Aim 1 of a larger project. The participants assigned to intervention in this trial completed either the DSGP supplementation or placebo arms. No aim 2/clinical trial phase 2 will be enacted for the larger project.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: participants that completed full study intervention with baseline and eight week assessment.

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 Glygocalyx Integrity - Perfused Boundary Region, measured over Change from baseline to eight weeks assessment.

The primary endpoint is change in perfused boundary region from baseline to the eight-week assessment, reported in delta micrometers. The registry describes measurement with the GlycoCheck instrument, a video microscope placed under the participant’s tongue. It assesses how far red blood cells penetrate into the glycocalyx lining. In the registry’s description, a larger perfused boundary region indicates lower glycocalyx integrity.

This measure is used as a non-invasive indicator of glycocalyx integrity. It is relevant to the trial’s stated rationale because the investigators propose that the endothelial glycocalyx may be involved in vascular responses. The endpoint is a measurement of the glycocalyx-related characteristic itself; it is not a direct measure of cardiovascular events, clinical symptoms, or exercise capacity.

The reported outcome is the mean change in each group, with standard errors reported as the measure of spread. The comparison of interest is the difference between those group means. The supplement group’s posted mean change was 0.11, while the placebo group’s was -0.16. The posted between-group mean difference was 0.27. A positive difference means the supplement group’s mean change was numerically higher than the placebo group’s mean change; because an increase in this measure indicates lower glycocalyx integrity, the direction should be interpreted in light of that measurement definition.

The endpoint summary is restricted to participants who completed the full intervention and had both baseline and eight-week assessments. The registry does not report how measurements were handled for participants without both assessments, nor does it provide further details about instrument quality control or the endpoint’s measurement properties.

7. Results Posted in the Registry

• Dietary Supplementation of Glycocalyx Precursors (DSGP): mean 0.11 versus -0.16 on control; difference 0.27 (95% CI -0.17 to 0.71), standardized effect d = 0.51; z-test p = 0.234.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical measurement of change in perfused boundary region. The registry reports means for the two groups and standard errors. A mean summarizes the center of a group’s measurements. The standard error describes the uncertainty in the estimated mean; it is not the standard deviation and does not show the full spread of individual participant measurements. These statistical concepts are general explanations.

What the mean difference represents

The between-group mean difference compares the supplement group’s average change with the placebo group’s average change. The posted estimate is 0.27. This is a comparison of changes over the stated period, rather than a comparison of the group means at baseline or at eight weeks separately. The registry’s outcome definition specifies change from baseline to the eight-week assessment. The sign of the estimate depends on the ordering of the groups, and the registry’s comparison presents dietary supplementation of glycocalyx precursors relative to placebo.

A mean difference preserves the original measurement scale, here delta micrometers. In general, this makes it possible to interpret the estimate in the units of the outcome. It does not, on its own, say whether the difference is important to participants or whether it has implications for health. The registry does not provide a threshold for a meaningful difference.

What the confidence interval adds

A confidence interval gives a range of estimates that are reasonably compatible with the observed data under the statistical procedure and assumptions used. This is a general explanation, not a guarantee that the true value lies within the particular interval. The posted interval for the between-group difference runs from -0.174 to 0.714. Because it includes zero, the data are compatible with no difference as well as with differences in either direction. The width also indicates that the point estimate is not highly precise.

The interval is more informative than the point estimate alone because it displays uncertainty. It should not be read as a range containing most individual participant changes; it concerns the estimated group difference. The registry does not identify the method used to construct the interval, so details such as the exact distributional assumptions and any adjustment are not reported in the registry record.

How to read the p-value

The unadjusted p-value is 0.234. In general, a p-value measures how compatible the data are with a null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The word unadjusted indicates that this posted value is not adjusted for multiplicity. The record does not report whether a different analysis or adjustment was prespecified.

The p-value should be read alongside the estimate and interval. It does not replace either of them. Here the estimate is positive, the interval includes zero, and the p-value is 0.234. Together, these describe an uncertain estimate rather than a precise finding. The registry record does not state the decision rule the investigators planned to use, so no claim about whether the result met the trial’s own prespecified criterion can be made.

What the group summaries do and do not show

The outcome summaries report 10 participants in the supplement group and 12 in the placebo group, with standard errors of 0.17 and 0.15. In general, unequal group sizes and the variability of observations affect the precision of an estimated comparison. The posted group standard errors are used in the results summary, but the registry does not provide participant-level data or group standard deviations. No distributional plots or model diagnostics are posted.

The listed primary analysis population includes participants who completed the full intervention and had both assessments. This is a complete-assessment population as described in the record. It is not possible to infer from this description how missing measurements were handled, whether participants were excluded for other reasons, or how the analysis might compare with an analysis of all randomized participants. Those details are not reported in the registry record.

Why over-dispersion can matter

In general, over-dispersion means that observed variability is larger than a model expects. When a model assumes less variability than is present, standard errors can be too small and intervals can be too narrow. Conversely, models that account for extra variability may produce wider uncertainty estimates. This trial’s primary outcome is continuous, and the registry does not report an over-dispersion model or diagnostics. This general concept should not be taken to mean over-dispersion was present in this trial.

The posted comparison is described as a mean difference and accompanied by an unadjusted p-value and confidence interval. The exact statistical model, covariates, handling of baseline measurements, and sensitivity analyses are not reported in the registry record. Without those details, the results can be interpreted at the level of the posted summary statistics, but the full analysis procedure cannot be reconstructed.

10. Confidence Intervals and Precision

The posted comparison estimates a between-group mean difference of 0.27. Its confidence interval runs from -0.174 to 0.714. The interval includes zero, meaning the posted data are compatible with no between-group difference as well as with values on either side of zero. It also spans values that differ substantially from the point estimate, so the estimate is not highly precise.

A confidence interval is a way to express uncertainty around an estimate. In general, a narrower interval indicates greater precision and a wider interval indicates less precision, given the same measurement scale. The interval applies to the estimated difference between group means, not to individual participants’ changes. The registry does not report the method used to calculate it, and it does not provide a clinically meaningful threshold against which to assess the interval.

The primary outcome summaries include 10 participants in the supplement group and 12 in the placebo group. The standard errors for the group means are 0.17 and 0.15. These summarize uncertainty in the group means, while the confidence interval summarizes uncertainty in the contrast. They are related concepts but are not interchangeable. The posted estimate should therefore be read with attention to both its direction and the range of uncertainty.

The unadjusted p-value is 0.234. This does not give the probability that the observed result is due to chance, and it cannot establish equivalence between the groups. The interval and p-value both convey uncertainty, but neither says whether a difference would matter in practice. The registry record does not report a threshold for clinical importance or a prespecified precision target.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table is a planning illustration based on the posted effect, not a record of the trial’s original design. Its figures are participants per arm, not total participants or total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider an effect equal to 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column indicates the illustrated number of participants per arm for an analysis to have 80% power under the listed assumptions and effect scenario. The 90% power column gives the corresponding planning figure for 90% power. Power is a property of a design under assumed conditions; it is not a guarantee that a study will detect an effect or that a result will be statistically significant.

For the scenario using 100% of the observed effect, the table shows 60 participants per arm for 80% power and 81 participants per arm for 90% power. For planning for 75% of the observed effect, it shows 107 participants per arm for 80% power and 143 participants per arm for 90% power. For planning for 50% of the observed effect, it shows 240 participants per arm for 80% power and 322 participants per arm for 90% power. The figures increase as the assumed effect gets smaller, because smaller effects are harder to distinguish from random variation under the same general planning framework.

These calculations are not observed power. They are illustrative planning numbers based on the observed effect, and they should not be mistaken for the number enrolled or the original rationale for the trial’s enrollment.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.270; pooled standard deviation σ = 0.528.
2. n = 2 × (1.96 + 0.842)² × 0.528² / 0.270² = 60.0, rounded up to 60 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.27                      # observed difference in means
sigma <- 0.527778362572775                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5205005)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 60 (80% power), 81 (90% power)
 75% of observed effect: n per arm = 107 (80% power), 143 (90% power)
 50% of observed effect: n per arm = 240 (80% power), 322 (90% power)
power.t.test: 61 
Simulated power at n = 60 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes in addition to the primary outcome: brachial artery flow mediated dilation, insulin-stimulated leg blood flow, and femoral artery flow mediated dilation. It reports four outcome measures overall, but no secondary analyses are posted. The results therefore do not permit a statistical assessment of those secondary outcomes.

Multiplicity arises when several hypotheses or outcomes are examined. In general, looking at many outcomes can increase the chance of at least one apparently unusual result, so a statistical plan may specify how to address that issue. The registry record does not report a multiplicity strategy, a testing hierarchy, or an adjusted p-value. The posted primary comparison is explicitly unadjusted. It is not possible to determine from the record whether the trial had an intended adjustment procedure or how secondary outcomes were to be interpreted.

The record identifies the primary outcome population as participants who completed the full intervention and had baseline and eight-week assessments. It does not report how many randomized participants lacked either measurement, the reasons for missingness, or how missing data were handled. It also does not report whether the analysis followed an intention-to-treat principle, whether participants were analyzed according to assigned group, or whether any per-protocol or sensitivity analyses were planned or conducted.

These omissions limit evaluation of possible selection effects and the robustness of the result. For example, the registry description alone cannot establish whether missing outcomes were unrelated to the measurements that would have been observed, or whether excluding participants with incomplete assessments affected the comparison. Those are general concerns when interpreting analyses restricted to people with complete measurements, not claims that such bias occurred.

The statistical analysis plan, interim-analysis information, covariate adjustments, and analysis-population definitions beyond the posted primary outcome description are not reported in the registry record. Consequently, the result should be interpreted as the posted unadjusted comparison, without assuming unreported analytic choices.

14. 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 registry reports serious adverse events for 12 participants at risk in each group. There were zero serious adverse events in the dietary supplementation group and zero in the placebo group. It also reports zero deaths in each group. These are the serious-event figures posted for the trial.

For other adverse events, 12 participants were at risk in each group. The registry reports 4 affected participants in the supplement group and 3 in the placebo group. These counts describe the posted adverse-event summary; they do not state the severity, duration, relatedness, or specific event terms. The registry does not post serious-event terms.

These figures should be read as counts in the registry, not as a complete safety profile. The record does not provide further details about event definitions, ascertainment, exposure time, or whether the events were considered related to the intervention. No interpretation beyond the posted counts is warranted.

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

The result describes the average change in perfused boundary region over eight weeks among participants represented in the primary outcome analysis. The estimated difference between dietary supplementation of glycocalyx precursors and placebo was 0.27. The confidence interval includes zero, and the unadjusted p-value was 0.234. These findings convey uncertainty around the estimated contrast rather than a precise estimate of the difference.

The endpoint is a measure used to assess glycocalyx integrity. The registry states that an increase in perfused boundary region indicates lower glycocalyx integrity. Therefore, the positive mean difference should be described as a numerically higher average change in the supplement group relative to placebo, not as evidence of improved integrity. The estimate does not by itself identify the biological reason for the observed group difference.

The result does not establish whether the intervention changes exercise-induced vascular adaptations, cardiovascular outcomes, or health outcomes. Although the registry’s rationale discusses exercise and vascular function, the primary posted result is for perfused boundary region. The listed secondary outcomes have no posted analyses in the record. The primary outcome also does not measure symptoms or exercise capacity.

The record’s analysis population is limited to participants who completed the full intervention and had both baseline and eight-week assessments. Missing-data handling and the trial’s original statistical plan are not reported. These gaps, along with the uncertainty shown by the interval, should be considered when judging how far the posted result can be generalized or how robust it may be.

In general, statistical evidence and clinical importance are different questions. A point estimate and its uncertainty describe the data on the measured scale; they do not establish whether an effect matters to participants. The registry does not report a clinically meaningful threshold for this endpoint. The result should therefore be read as a comparison of the posted measurements, without turning it into a treatment recommendation or a claim about broader clinical benefit.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it evaluates a continuous physiological measure in a randomized comparison and reports both group means and a between-group estimate. The contrast is more informative than looking at a change within one arm alone: it directly describes how the average change in perfused boundary region differed between the supplement and placebo groups.

The estimate is accompanied by a confidence interval and an unadjusted p-value. Seeing the interval makes the uncertainty visible: it includes zero and extends in both directions around the point estimate. This is a useful reminder that a numerical difference is not necessarily estimated precisely. The small primary outcome analysis counts, 10 and 12 participants, are also important context for reading that uncertainty.

The endpoint has a clear measurement interpretation in the registry: it assesses red blood cell penetration into the glycocalyx, and higher perfused boundary region indicates lower glycocalyx integrity. That definition matters because the direction of a numerical change should not be casually equated with benefit. Statistical interpretation depends on both the comparison and what the measure represents.

The record also illustrates the limits of registry results. Although several secondary outcomes are listed, no analyses are posted for them. The analysis plan, missing-data procedures, multiplicity approach, and original sample-size rationale are not reported in the registry record. Those omissions prevent a fuller assessment of how the posted primary result fits the investigators’ planned statistical framework.

The sample-size illustrations help show how planning requirements depend on the assumed effect and target power, but they are separate from the trial’s original enrollment decisions. Together, the posted outcome and planning displays support careful attention to effect size, precision, analysis population, and transparency about methods.

17. 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 outcome analysis includes 10 participants in the supplement group and 12 in the placebo group. The registry describes these as participants who completed the full intervention and had both baseline and eight-week assessments. It does not explain the difference between these analysis counts and total enrollment of 24, or report the number and reasons for any incomplete assessments.

The record does not describe how missing outcome data were handled, whether the analysis included all randomized participants, or whether sensitivity analyses were conducted. These details matter because the posted analysis population is defined by completing the intervention and having both measurements. The record does not establish whether this restriction affected the comparison.

The statistical model, covariate adjustment, method for the confidence interval, and prespecified analysis plan are not reported in the registry record. The posted p-value is unadjusted, while the record lists multiple outcomes and does not describe a multiplicity plan. No analyses are posted for the secondary outcomes.

The endpoint is a measurement of glycocalyx integrity, not a direct measure of clinical outcomes or exercise-induced vascular adaptations. The record does not provide a threshold for a clinically meaningful difference. It also does not report measurement reliability or additional instrument procedures beyond the description of the GlycoCheck assessment.

Safety reporting is limited to the posted counts of participants affected by serious and other adverse events and deaths. Specific terms and details about severity, relatedness, and event ascertainment are not reported. These limitations restrict interpretation to the registered summaries and leave important questions about analysis methods, missingness, and broader relevance unresolved.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes — NCT05205005.
• Registry record last updated 2025-05-02; status last verified 2025-04.
• Results first posted 2025-04-02.
• 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.

21. Record Summary

The registry record describes a completed, randomized, quadruple-masked, parallel-group phase 2 and phase 3 trial with enrollment of 24 participants. It compares eight weeks of dietary supplementation of glycocalyx precursors with placebo in participants with type 2 diabetes. The primary endpoint is change in perfused boundary region from baseline to the eight-week assessment.

The posted primary outcome comparison has a mean difference of 0.27, a confidence interval from -0.174 to 0.714, and an unadjusted p-value of 0.234. The analysis includes 10 participants in the supplement group and 12 in the placebo group. The registry lists three secondary outcomes but posts no analyses for them.

The record reports zero serious adverse events and zero deaths in each group, with 4 and 3 participants affected by other adverse events in the supplement and placebo groups, respectively. Details of the original sample-size rationale, analysis plan, and missing-data handling are not reported in the registry record.