Angiotensin II Blockade and Inflammation in Obesity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Angiotensin II Blockade and Inflammation in Obesity (NCT01684748), a randomized phase 4 study. The primary outcome is Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time).

2. Clinical Question

3. Trial Design

This is a completed phase 4 randomized study with a crossover model and no masking. The registry records enrollment of 20. Its summary describes a planned study of 44 people, whereas the primary outcome description reports that 16 participants took part in all or some measurements and that only 10 had complete or sufficient data for analysis for each intervention. The difference between the planned count and the recorded enrollment is a feature of the registry information; reasons for it are not reported in the registry record.

The two intervention conditions were olmesartan medoxomil and no drug intervention. Participants were assigned to sequences: olmesartan first followed by no drug, or no drug first followed by olmesartan. Each intervention period is described as 8 weeks. The no-drug-first sequence description specifies a 2-week washout before the olmesartan period. The other sequence description is truncated, and a complete account of washout procedures is not reported in the registry record.

The available dosing description states that olmesartan began at 20 mg daily for 2 weeks and then increased to 40 mg daily for the remaining 6 weeks, with the dose remaining at 20 mg if blood pressure fell below 110/70. The registry does not give enough complete text to establish every dosing detail for both sequences. Allocation concealment, the randomization method, and procedures used to maintain or assess adherence are not reported in the registry record.

The primary outcome was a continuous measure: change in insulin sensitivity from baseline to post-testing after an 8-week intervention. Results are reported separately for the two interventions. Although a crossover design can use within-participant comparisons, the posted summary does not provide the paired participant-level differences or an analysis accounting for within-person correlation. The registry lists no posted analysis records. The trial’s original statistical analysis plan and design assumptions 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.

First Intervention - 8 Weeks

Second Intervention - 8 Weeks

Analysis population for the primary outcome, as defined in the registry: Results of insulin sensitivity by intravenous glucose tolerance (IVGTT) testing are reported per intervention (Olmesartan Medoxomil and No drug). Only 10 of the 16 study participants who participated in all or some of the study measurements opted to complete or had sufficient data to analyze for each pre- and post-intervention (4 total) IVGTT.

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 Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time), measured over Baseline testing to post-testing after 8-week intervention.

The primary endpoint is change in insulin sensitivity, measured using intravenous glucose tolerance testing (IVGTT), from baseline to post-testing after an 8-week intervention. The reported unit is mu/L/min. During an IVGTT, glucose and insulin concentrations are collected over time after glucose is administered. The registry description states that glucose was measured with a YSI glucose analyzer and insulin with ELISA colorimetric kits after study samples had been collected.

The recorded glucose and insulin values were entered into MINMOD software. The description says that MINMOD applies Bergman’s minimal model to estimate insulin sensitivity from the IVGTT measurements. The registry specifies 33 measurement timepoints over a 3-hour protocol. The resulting insulin-sensitivity value was determined at baseline and after the intervention; the change between those assessments was then calculated for each intervention.

As a continuous endpoint, the measure can represent both the direction and magnitude of change rather than assigning participants to a simple event/no-event category. In general, a continuous physiological measure may retain more gradation than a binary outcome. The endpoint’s interpretation depends on the measurement process and the model used to derive the value. The registry does not report further validation details, the handling of values outside expected ranges, or the clinical importance of a particular change in this measure.

7. Results Posted in the Registry

• No Drug Intervention: mean -0.80 versus 0.25 on control; difference -1.06 (95% CI -3.22 to 1.10), standardized effect d = -0.43; z-test p = 0.337.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, so its results are reported as means with standard deviations. A mean describes the average observed change in the contributing participants. A standard deviation describes how dispersed individual values are around that average; it is not the uncertainty around the mean. The olmesartan mean change is 0.253 mu/L/min with a standard deviation of 2.7, and the no-drug mean change is -0.804 mu/L/min with a standard deviation of 2.2. Each intervention summary has 10 participants.

What does the contrast represent?

The posted contrast is -1.057 mu/L/min, calculated as the no-drug mean minus the olmesartan mean. A negative contrast therefore indicates that the posted mean change was lower under no drug than under olmesartan on the reported scale. This direction is a description of the arithmetic contrast, not a conclusion about the clinical value of either condition. The registry reports the contrast with a confidence interval from -3.216 to 1.102 and an unadjusted p-value of 0.337.

The contrast is an unadjusted recalculation from the posted summary statistics, not a posted sponsor analysis. In general, an unadjusted comparison does not account for additional covariates or design features unless those are built into the calculation. The registry does not provide an analysis record describing how the reported outcome was statistically analyzed, and it does not give participant-level observations. The contrast should therefore not be mistaken for a documented model-based analysis of the crossover design.

Why does crossover structure matter?

In a crossover study, a participant may receive more than one intervention at different times. Measurements from the same person are generally related, rather than independent. In general, accounting for this within-person relationship can affect both the estimated contrast and its standard error. A paired comparison uses each participant’s results across conditions, while a comparison that treats condition summaries as separate groups does not make that pairing explicit.

The registry gives intervention-specific means and standard deviations but does not report paired differences, the within-participant correlation, period-specific results, or a model including sequence and period. The available summary therefore cannot reproduce a full crossover analysis. It also cannot establish whether participants contributed data under both conditions or whether the two sets of 10 observations overlap completely.

How should the p-value be read?

The unadjusted p-value is 0.337. In general, a p-value describes how unusual a test statistic at least as far from the null value would be under a specified statistical model if the null hypothesis were true. It is not the probability that the null hypothesis is true, and it does not measure the probability that chance alone caused the observed result. Its interpretation depends on the model and test used. The registry does not report the original test or analysis specification, so the p-value should be interpreted alongside the uncertainty interval and the limited outcome sample.

A p-value above a conventional significance threshold does not demonstrate that two conditions are identical. Demonstrating equivalence or non-inferiority would require a suitable prespecified margin and an analysis designed for that purpose; such a margin and analysis are not reported in the registry record. Here, the confidence interval spans zero and a broad range of contrasts, so the central statistical issue is uncertainty rather than evidence of equivalence.

What does the confidence interval add?

In general, a confidence interval describes the range of parameter values compatible with the data and the assumptions of the method used. A 95% confidence interval procedure is designed so that, over repeated samples under its assumptions, intervals constructed by that procedure would cover the true parameter at the stated rate. It does not mean there is a 95% probability that this particular fixed interval contains the true value. The interval from -3.216 to 1.102 makes clear that the estimated contrast is not precise enough to distinguish confidently among materially different possibilities on the outcome scale.

Because the study is small and the primary outcome includes only 10 participants per intervention, the estimate may be sensitive to individual observations. That is a general concern with limited samples, not a claim about any particular participant’s value. The standard deviations are large relative to the reported means, indicating substantial spread in observed changes. The registry does not report the distribution of individual values, so skewness, outliers, or other distributional features cannot be assessed from these summaries.

No adjustment for multiple comparisons is described in the registry record. The record lists two outcome measures, but it posts no secondary outcome analyses and no analysis records. The reported p-value is explicitly unadjusted. Whether the original study had a multiplicity strategy, prespecified analysis hierarchy, or additional planned outcomes is not reported in the registry record.

General statistical interpretation also depends on how missing values, protocol deviations, and analysis populations were handled. The registry says that only 10 participants had complete or sufficient data for each intervention outcome, but does not explain the reasons, exclusions, or imputation approach. It is therefore not possible to determine whether the posted summaries follow an intention-to-treat, per-protocol, or another population definition.

10. Confidence Intervals and Precision

The estimated no-drug-minus-olmesartan contrast is -1.057 mu/L/min. Its 95% confidence interval extends from -3.216 to 1.102 mu/L/min. The interval includes zero and extends in both directions, so the data do not pin down the contrast’s direction or magnitude with much precision. Values indicating a lower mean under no drug, no difference, and a higher mean under no drug all fall within the reported interval.

A confidence interval is an uncertainty range calculated using a statistical procedure and its assumptions. In general, a 95% confidence interval procedure would cover the true contrast in 95% of repeated samples if its assumptions held. It does not assign a 95% probability to the true value being inside this one interval. The interval’s width is a useful indication of the limited precision in the posted estimate, but its validity also depends on the analysis method.

The summaries include 10 participants per intervention, with standard deviations of 2.7 for olmesartan and 2.2 for no drug. The registry does not provide the paired participant-level results needed to assess within-person variability in this crossover study. As a result, the interval reported with the simple contrast may not reflect all the design information that a full paired analysis could use. The original analysis method is not reported in the registry record.

The interval should not be treated as a range of values that the outcome itself can take; it concerns the estimated contrast. Nor does its inclusion of zero prove the conditions are equivalent. A narrower interval would give more precise information about the contrast, while this interval leaves considerable uncertainty about both direction and size.

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 planning figures are participants per arm, not total event counts. They are illustrations calculated from the observed effect rather than a report of the trial’s own original sample-size design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect if that effect were the true one and the planning assumptions held. The 90% power column gives the corresponding per-arm count for a 90% chance. These are prospective planning quantities, not statements about what happened in this study.

For planning based on 100% of the observed effect, the estimates are 86 participants per arm for 80% power and 115 for 90% power. For 75% of the observed effect, they are 152 per arm and 203 per arm. For 50% of the observed effect, they are 341 per arm and 457 per arm. Smaller target effects require more participants because they are harder to distinguish from random variation under the same assumptions.

These calculations are not observed power. They do not describe the probability that the completed study detected an effect, and they are not evidence that the observed contrast is the true effect. They are planning illustrations based on the posted observed effect and specified assumptions; the trial’s original design assumptions are not reported in the registry record.

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 = -1.057; pooled standard deviation σ = 2.463.
2. n = 2 × (1.96 + 0.842)² × 2.463² / -1.057² = 85.2, rounded up to 86 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 <- -1.057                      # observed difference in means
sigma <- 2.46272207120495                     # 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(1684748)
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 = 86 (80% power), 115 (90% power)
 75% of observed effect: n per arm = 152 (80% power), 203 (90% power)
 50% of observed effect: n per arm = 341 (80% power), 457 (90% power)
power.t.test: 86.2 
Simulated power at n = 86 per arm: 0.799 (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 two outcome measures, but the primary insulin-sensitivity outcome is the one described in detail. It reports zero analysis records and zero posted secondary outcomes. The registry record does not state whether the investigators prespecified an outcome hierarchy, adjusted for multiple comparisons, or planned any particular method for controlling type I error across outcomes. Those features are not reported in the registry record, so the unadjusted p-value should not be assumed to account for testing beyond this contrast.

There is also incomplete information about missing outcome data. The primary outcome description says that 16 participants completed all or some study measurements, while only 10 had sufficient data to analyze for each intervention. The reasons that other participants did not contribute usable results are not reported in the registry record. The record does not say whether missingness resulted from incomplete testing, unusable samples, withdrawal, or another reason, and none of these explanations should be inferred.

It is not reported whether the same 10 participants contributed data under both interventions. The registry does not provide participant-level paired results, a flow of participants through each period, or details of how missing values were handled. Imputation, complete-case analysis, and any sensitivity analysis are not reported in the registry record.

The analysis population is likewise not defined. The registry does not state whether results were based on all randomized participants, participants who completed both periods, participants with adequate measurements, or another group. No intention-to-treat or per-protocol analysis is described. In a crossover study, information about sequence completion and period-specific missingness is relevant to interpreting the paired contrast, but these details are not reported in the registry record.

The original statistical analysis plan, the handling of protocol deviations, and any interim analyses are not reported in the registry record. Without these details, the posted summary supports interpretation of the means and contrast as recorded, but not a determination of whether the analysis followed a prespecified strategy.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse events for 16 participants at risk in the olmesartan group and 16 at risk in the no-drug group. The number affected by serious adverse events is recorded as 0 in each group. Other adverse events are also recorded as 0 among 16 participants at risk in each group. These are the event counts posted for the listed groups.

These entries should be read as registry-reported counts, not as proof that no adverse events of any kind occurred during the study. The record does not give descriptions of non-serious events because the affected counts are recorded as zero, and it lists no serious adverse-event terms. Death counts are not reported in the registry record.

The safety counts are based on groups of 16, whereas the primary insulin-sensitivity summaries include 10 participants per intervention. The registry does not explain the different denominators or provide further detail on safety follow-up duration, event ascertainment, or how adverse events were attributed to an intervention period. The counts therefore describe what is posted, with those reporting details left unspecified.

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

The result describes a small set of posted insulin-sensitivity measurements after olmesartan medoxomil and no-drug intervention. The mean changes were 0.253 mu/L/min and -0.804 mu/L/min, respectively. The estimated no-drug-minus-olmesartan contrast was -1.057 mu/L/min, with a 95% confidence interval from -3.216 to 1.102 and an unadjusted p-value of 0.337. The interval shows that the estimate is uncertain and compatible with contrasts in either direction.

These data do not establish that the interventions produce the same insulin-sensitivity change, nor do they establish a reliable difference. Equivalence cannot be inferred simply because the interval includes zero or because the unadjusted p-value is 0.337. The registry does not report a prespecified equivalence margin or a formal equivalence analysis.

The outcome concerns insulin sensitivity estimated from an IVGTT and MINMOD, not a direct measure of adipose-tissue inflammation, skeletal-muscle inflammation, cardiovascular outcomes, or long-term clinical events. Although the study’s summary describes broader questions about angiotensin II blockade and inflammation, the posted primary results do not answer those broader questions. In particular, there are no posted secondary outcome results in the registry record.

The interpretation is limited by the small number contributing to the outcome and by incomplete reporting of participant-level crossover data. The registry does not establish whether the same participants contributed to both intervention summaries, how incomplete measurements were handled, or whether period and sequence effects were considered. These gaps make it difficult to determine how closely the posted contrast reflects a complete within-person comparison.

The findings are specific to the reported study population, interventions, measurement procedures, and available observations. They should not be generalized beyond those data or treated as a treatment recommendation. They also do not show that any particular change in the endpoint is clinically important; that threshold is not reported in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates an important statistical distinction between an estimated effect and the precision with which it is known. The contrast is -1.057 mu/L/min, but its confidence interval extends from -3.216 to 1.102. A single point estimate can look definite when written by itself; the interval shows that the available measurements leave substantial uncertainty about the size and direction of the contrast.

The crossover design also highlights the value of matching the analysis to the study structure. In general, repeated measurements from the same participant are related. A complete crossover analysis can account for this pairing and for possible period or sequence effects. The registry provides intervention-specific summaries but does not report the paired differences or such a model, so readers cannot assess how those design features were handled in the original analysis.

The gap between enrollment and the outcome sample further matters. The registry records enrollment of 20, while the study summary describes a planned 44 and the primary outcome description says 16 participants took part in all or some measurements, with 10 supplying sufficient data for each intervention. The reasons for these counts and the handling of unavailable measurements are not reported. Clear accounting of participant flow and missing outcomes is essential for understanding which observations support an estimate.

Finally, the planning illustrations show why effect-size assumptions matter. Under the stated planning method, smaller target effects correspond to larger participant counts per arm. Those numbers are not the completed trial’s observed power or original design justification. Keeping that distinction clear helps readers avoid treating a planning exercise based on an observed estimate as evidence about the certainty of the result.

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 results include 10 participants per intervention, while the registry records enrollment of 20 and describes 16 participants as completing all or some study measurements. The registry summary also describes a planned sample of 44. Reasons for the difference between planned enrollment, recorded enrollment, and the outcome analysis counts are not reported in the registry record.

The crossover design would ordinarily make within-participant information relevant, but the posted results do not identify whether the two groups of 10 contain the same participants. Paired differences, period-specific measurements, sequence effects, and within-person correlation are not reported. The unadjusted contrast available from the summary statistics therefore cannot show how a full crossover analysis might differ.

The arm descriptions are incomplete. One sequence description specifies a 2-week washout, while the other is truncated; complete washout procedures are not reported in the registry record. The olmesartan dosing description is also incomplete, so the available text does not establish every detail of treatment delivery in both sequences. Adherence and allocation concealment procedures are not reported.

The record does not report the original sample-size justification, the statistical analysis plan, handling of missing data, the analysis population, or any interim-analysis plan. It also lists no analysis records and no posted secondary outcome results. The available safety entries do not describe follow-up duration or event ascertainment, and death counts are not reported in the registry record.

These reporting limitations do not alter the posted means, contrast, or confidence interval, but they constrain what can be concluded about how those estimates were generated and how broadly they apply.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Angiotensin II Blockade and Inflammation in Obesity — NCT01684748.
• Registry record last updated 2018-01-03; status last verified 2017-12.
• Results first posted 2015-01-12.
• 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

NCT01684748 is a completed, randomized, unmasked, phase 4 crossover study sponsored by Virginia Polytechnic Institute and State University. It records enrollment of 20 and compares olmesartan medoxomil with no-drug intervention across 8-week intervention periods.

The primary outcome is change in insulin sensitivity measured with IVGTT and MINMOD. Results are reported for 10 participants per intervention: a mean change of 0.253 mu/L/min with olmesartan and -0.804 mu/L/min with no drug. The no-drug-minus-olmesartan contrast is -1.057 mu/L/min, with a 95% confidence interval from -3.216 to 1.102 and an unadjusted p-value of 0.337.

The registry reports zero serious and other adverse events among 16 participants at risk in each intervention group. It does not report death counts. The original statistical plan, analysis population, handling of missing outcome data, and complete crossover analysis details are not reported in the registry record.