This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude (NCT06164665), a randomized phase 4 study. The primary outcome is Rate of Exogenous Glucose Oxidation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06164665 |
| Phase | Phase 4 |
| Condition | High Altitude |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 9 |
| Arms in the primary outcome | 2 |
| Lead sponsor | United States Army Research Institute of Environmental Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns healthy, recreationally active male lowlanders undergoing acute high-altitude exposure and steady-state exercise. The brief summary says eight participants between 18-39 years were required, while the registry lists enrollment as 9. The outcome entries report 7 participants in each condition; the registry record does not explain the relationship between these counts.
Intervention
Pioglitazone was administered orally at 15 mg per day for 5 days, according to the arm description. The study summary describes a glycogen normalization period and exercise trials after daily pioglitazone or placebo. The primary question is whether the pioglitazone condition changes exogenous glucose oxidation during exercise at high altitude.
Comparator
The comparator was a matched placebo, described in the arm information as a microcrystalline cellulose pill given orally once per day for 5 days. The record describes a randomized, double-blind crossover comparison. The available outcome results are reported by condition, but do not include participant-level paired results.
Primary question
The primary endpoint was the rate of exogenous glucose oxidation, measured in g/min. The study aimed to compare that rate during metabolically matched, steady-state exercise under acute high-altitude exposure after pioglitazone or placebo. The registry reports condition-specific means and standard deviations, but a treatment-effect estimate and its uncertainty are not reported in the registry record.
3. Trial Design
This completed phase 4 study is registered as a randomized, double-blind, placebo-controlled crossover trial. The sponsor is the United States Army Research Institute of Environmental Medicine. Its title identifies the focus as pioglitazone and exogenous carbohydrate oxidation during steady-state exercise at high altitude. The record lists High Altitude as the condition.
The study summary describes acute high-altitude exposure and metabolically matched steady-state treadmill exercise. It specifies an exposure of approximately 5 h, with barometric pressure described as 460 mmHg and altitude as 4300m. The planned exercise trials are described as 80-min sessions at the same absolute workload, corresponding to approximately 55 ± 5% of V̇O2peak at high altitude. Participants consumed 145 g of glucose, according to the summary. These are descriptions of the study conditions, not outcome results.
The two treatment conditions were pioglitazone and placebo. The arm descriptions specify a daily oral dose for 5 days in each condition. The summary also describes a 4 day glycogen normalization period while receiving the assigned treatment. The registry record does not clarify how this description relates to the 5-day treatment duration in the arm descriptions, or how the sequence and timing of the crossover periods were organized.
The registry lists enrollment as 9, whereas the study summary says eight healthy, recreationally active males were required. Outcome data are posted for 7 participants in each condition. Because a crossover study measures participants under both treatments, the condition-specific entries should not be interpreted as independent groups. The record does not report participant-level paired measurements, treatment sequence, washout details, or a statistical analysis plan.
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 (5 days)
| Stage | Pioglitazone First, Then Placebo | Placebo First, Then Pioglitazone |
|---|---|---|
| STARTED | 4 | 4 |
| COMPLETED | 3 | 4 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Pioglitazone First, Then Placebo | Placebo First, Then Pioglitazone |
|---|---|---|
| Adverse Event | 1 | 0 |
Washout (2 weeks)
| Stage | Pioglitazone First, Then Placebo | Placebo First, Then Pioglitazone |
|---|---|---|
| STARTED | 3 | 4 |
| COMPLETED | 3 | 4 |
| NOT COMPLETED | 0 | 0 |
Second Intervention (5 days)
| Stage | Pioglitazone First, Then Placebo | Placebo First, Then Pioglitazone |
|---|---|---|
| STARTED | 3 | 4 |
| COMPLETED | 3 | 4 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Pioglitazone First, Then Placebo | Placebo First, Then Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 4 | 8 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 4 | 8 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 22 (SD 4) | 26 (SD 8) | 23 (SD 6) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 4 | 4 | 8 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 4 | 4 | 8 |
| High Altitude VO2peak | ml/kg/min | 31 (SD 2) | 35 (SD 4) | 33 (SD 3) |
6. Primary Endpoint
The registry lists the primary outcome as Rate of Exogenous Glucose Oxidation, measured over 8 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | g/min |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the rate of exogenous glucose oxidation, reported as a mean in g/min with standard deviations. Exogenous glucose is carbohydrate consumed from outside the body; its oxidation rate describes how much of that ingested glucose is used through oxidative metabolism over the measurement period. This is distinct from total carbohydrate oxidation, which can include carbohydrate from endogenous stores.
The registry describes the objective as determining the effects of pioglitazone on exogenous glucose oxidation during exercise under acute high-altitude exposure compared with placebo. It also identifies the broader scientific motivation: hypoxia-related changes in insulin sensitivity and glucose kinetics may affect peripheral glucose uptake and oxidation. That rationale provides context for choosing the endpoint, but the posted aggregate outcome values do not establish the biological mechanism behind any observed difference.
The specified timeframe is 8 hours. The study summary separately describes exercise trials lasting 80 min under acute high-altitude exposure. The registry record does not explain the measurement schedule underlying the 8-hour endpoint timeframe, so the timeframe should be read as recorded rather than assumed to mean a particular sampling interval or continuous measurement period.
A mean describes the central value of the recorded endpoint within a condition, while the standard deviation describes variability among observations. Those summaries help characterize the data, but by themselves do not quantify the paired treatment effect in a crossover trial. A paired contrast and its uncertainty are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome gives a mean exogenous glucose oxidation rate of 0.31 g/min in the pioglitazone condition, with a standard deviation of 0.03, and 0.32 g/min in the placebo condition, with a standard deviation of 0.09. Each condition has an outcome count of 7. These are descriptive summaries of the registry results. They are not, on their own, an estimate of the within-participant treatment effect.
The crossover design makes the relationship between the two measurements important. Each participant may contribute observations under both treatments, so inference usually depends on the paired differences and on how those differences vary across participants. The registry record does not report those paired data, a paired treatment-effect estimate, a confidence interval, or a test result. Its analysis entry states that values are missing or not estimable for a two-arm comparison of this continuous endpoint. No inferential comparison should therefore be inferred from the two means alone.
The displayed standard deviations describe spread within each condition. They do not reveal whether participants with higher oxidation under placebo also had higher oxidation under pioglitazone, or whether individual responses tended to move in the same direction. That within-person association is central to assessing precision in a crossover analysis. Aggregate means and standard deviations cannot recover it.
The outcome counts also need to be read alongside the enrollment information. The registry lists enrollment as 9, the study summary says eight healthy males were required, and the outcome entries report 7 in each condition. The record does not report why those counts differ or whether the same participants contributed to both conditions. No assumptions about completion, exclusions, or missing measurements can be made from these values alone.
The two secondary outcomes listed are concentration of Interleukin-6 and concentration of Serum Hemoglobin. The record identifies these outcomes but provides no posted results for them in the registry record for this analysis. The primary outcome summaries therefore should not be taken as a complete account of all planned measurements.
In practical statistical terms, the posted results describe the observed condition-level means and variability, while leaving the comparative uncertainty unresolved. A reader can see what values were reported, but cannot determine from these summaries alone how precisely the within-participant effect was estimated or whether a formal comparison was performed. The registry record does not report a statistical analysis plan, adjustment strategy, or explanation for the unavailable comparison.
9. Statistical Methods Explained
For a continuous outcome, the mean summarizes the average measured value in a condition. Here, the outcome is a rate in g/min, and the registry reports a mean and standard deviation for each treatment condition. The standard deviation describes how spread out individual observations are around a condition mean. It is not a confidence interval and does not directly state the precision of the treatment comparison.
Why does the crossover structure matter?
In a crossover design, participants receive both conditions, and the comparison is generally based on within-participant contrasts. Each participant serves as their own comparator, which can account for stable differences between people. However, the analysis must retain the link between each participant's measurements. Condition-level means and standard deviations do not preserve that pairing. Without paired observations or a reported paired estimate, the treatment contrast and its standard error cannot be reconstructed reliably from these summaries.
The record identifies the trial as randomized, double-blind, and crossover, but does not report the treatment sequence, any washout period, or the statistical model used. Those details can matter when interpreting crossover data, including whether treatment order or period effects were considered. Their absence does not prove that such features were ignored; it means they are not reported in the registry record.
What do standard deviations tell the reader?
A standard deviation is a measure of dispersion among observations, expressed in the same units as the outcome. It helps distinguish a tightly clustered set of values from a more variable set, but does not describe the precision of a treatment-effect estimate by itself. Precision also depends on the number of analyzed observations and, in a crossover study, on the variability of the paired differences. Neither the paired-difference variability nor a confidence interval for the contrast is reported.
A confidence interval, as a general statistical concept, gives a range of values compatible with the data and the statistical method under stated assumptions. It communicates uncertainty around an estimate rather than merely describing variation between observations. No confidence interval for the treatment comparison is reported in the registry record. Consequently, the posted means should not be read as establishing the precision of the difference.
Why is no recalculated comparison presented?
The record indicates that a two-arm comparison for the continuous endpoint is not estimable from the posted information. This is consistent with the missing ingredients for a crossover reanalysis: the condition-specific summaries do not disclose each participant's paired measurements or their covariance. Computing an unpaired comparison instead would impose a different structure from the registered crossover design and would not recover the intended within-participant contrast. No recalculated effect or p-value is therefore reported.
A p-value, as a general concept, assesses how compatible observed data are with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment has an effect, and it does not express the size or practical importance of an effect. Since no comparison test result is reported, no p-value interpretation is possible. The record also does not report a multiplicity adjustment or a prespecified testing hierarchy.
How should sample-size illustrations be understood?
Planning illustrations based on an observed effect are not the trial's original sample-size justification and are not observed power. The registry record describes the illustration assumptions as a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. For a continuous endpoint, such an illustration may express participants per arm for 80% power or another stated target, if those outputs are available. These quantities describe hypothetical planning under assumptions; they are not evidence about the probability that the completed study detected an effect.
The observed-effect approach is especially dependent on the underlying effect estimate and its uncertainty. The registry information available for this analysis does not report an estimable paired treatment effect, and no numeric planning results are reported in the registry record. Any sample-size illustration should therefore be read as a planning exercise only, not as a property of the completed trial or a substitute for its analysis.
Why can variability matter beyond the mean?
When a measure varies more than a simple model expects, over-dispersion can make standard errors too small if the model fails to account for it. As a general principle, the model should reflect the outcome's distribution and design. The primary outcome is continuous, and the registry reports means and standard deviations rather than the raw distribution. The record does not report diagnostic checks or the model used to account for variability. It is therefore not possible to assess distributional assumptions from the posted summaries alone.
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.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Pioglitazone | 7 | 0.310 | 0.030 | 0.282 to 0.338 |
| Placebo | 7 | 0.320 | 0.090 | 0.237 to 0.403 |
R code and output
arm <- c("Pioglitazone", "Placebo")
n <- c(7, 7)
m <- c(0.31, 0.32)
sp <- c(0.03, 0.09)
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 Pioglitazone 7 0.310 0.030 0.282 0.338
CARM Placebo 7 0.320 0.090 0.237 0.40311. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary outcome as rate of exogenous glucose oxidation and identifies two secondary outcomes: concentration of Interleukin-6 and concentration of Serum Hemoglobin. It does not report a testing hierarchy, a multiplicity adjustment, or a statistical analysis plan. Without that information, readers cannot determine how the investigators intended to manage the chance of false-positive findings across multiple outcomes or analyses. No correction or interpretation should be assumed.
The primary endpoint has condition-specific means, standard deviations, and outcome counts, but a two-arm comparison is marked as missing or not estimable. The record does not report paired observations, a treatment-effect estimate, a confidence interval, or a p-value. It also does not explain why the comparison is unavailable. The distinction is important: descriptive results exist, but the registry does not provide an inferential result for the primary treatment contrast.
The registry enrollment count is 9, while the summary describes eight males as required and the outcome entries report 7 for each condition. The record does not explain these differences, identify an analysis population, or describe how missing observations were handled. It does not report whether all randomized participants were included in the outcome summaries or whether exclusions occurred. In a crossover trial, the availability of both treatment-period measurements can affect which participants contribute to a paired comparison; the record does not give that information.
Thus, the posted data support a limited descriptive reading. The study's missing analysis details should not be filled in by assuming an intention-to-treat, per-protocol, or other analysis population. Missingness mechanisms, reasons for incomplete data, and sensitivity analyses are not reported in the registry record.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pioglitazone | 0 | 8 | 0.0% |
| Placebo | 0 | 7 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pioglitazone | 0 of 8 |
| Placebo | 0 of 7 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pioglitazone | 1 of 8 |
| Placebo | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pioglitazone | Placebo |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 8 | 0 of 7 |
The registry reports no serious adverse events in either condition: 0 among 8 at risk in the pioglitazone group and 0 among 7 at risk in the placebo group. It reports 1 other, non-serious adverse event among 8 at risk in the pioglitazone group and 0 among 7 at risk in the placebo group. Deaths are reported as 0 in each group. No serious adverse-event terms are listed.
These entries are counts, not a complete account of the nature, timing, severity, or relatedness of each event. The record does not report whether the at-risk groups correspond to all enrolled participants, all participants exposed to each condition, or another safety population. Because this was a crossover study, the same participant may have received both conditions; the group counts should not be treated as independent participant groups or added together to estimate a unique participant total.
Zero reported serious events in these entries does not establish that serious events are impossible or that the treatment is safe in other settings. Likewise, the single other event reported in the pioglitazone group does not by itself establish causation. These small registry counts are best read as the safety events reported for this study, with no further conclusions about comparative risk warranted from the available information.
13. What the Result Does, and Does Not, Mean
The result provides descriptive information about exogenous glucose oxidation during exercise under acute high-altitude exposure in the two treatment conditions. The registry reports means of 0.31 g/min for pioglitazone and 0.32 g/min for placebo, alongside standard deviations of 0.03 and 0.09, respectively. These values characterize the posted condition summaries, not a formally estimated effect of pioglitazone.
The crossover design means that a direct comparison should account for the fact that measurements are paired within participants. Since the registry does not report the paired treatment contrast or its uncertainty, the condition means cannot establish the direction, magnitude, or precision of the average within-participant effect. They also do not support a conclusion about statistical significance. The record marks the two-arm continuous comparison as not estimable from the posted information.
The registry's study rationale concerns insulin sensitivity, glucose kinetics, and carbohydrate oxidation during acute high-altitude exercise. The primary endpoint is relevant to that research question, but the reported summaries do not demonstrate why any individual measurement occurred or establish a mechanism. Secondary outcomes for Interleukin-6 and Serum Hemoglobin are listed, but their results are not included in the available record details.
The outcome values also should be interpreted in the context of the reported counts. Enrollment is listed as 9, the brief summary says eight participants were required, and the outcome summaries list 7 in each condition. The registry record does not explain the difference or describe missing data. The available figures therefore do not show whether the analyzed measurements represent all randomized participants or how incomplete observations were handled.
Overall, the posted data describe the measured condition-level averages and variability, but do not provide the inferential comparison needed to quantify the treatment effect. They do not establish that pioglitazone changes or does not change exogenous glucose oxidation, and they do not determine the effect in populations or settings beyond the registered study conditions.
14. Why This Trial Matters Statistically
This trial is statistically notable because it uses a randomized, double-blind crossover design for a physiological outcome measured under controlled exercise conditions. Such a design can support efficient within-participant comparison when measurements from both treatment periods are available and analyzed as paired data. That advantage depends on preserving the participant-level relationship between observations.
The registry illustrates the limits of interpreting aggregate summaries without that relationship. Means and standard deviations describe each condition separately, but they do not reveal the variability of the paired differences. A treatment comparison may be more or less precise depending on how strongly a participant's measurements under the two conditions are related. Since the paired data and comparative estimate are not reported, the primary inferential question remains unanswered by the posted summaries.
The difference between enrollment, the number described as required, and the outcome counts also matters for transparent reporting. These counts are not interchangeable, and in a crossover study the number listed for each condition does not necessarily represent separate sets of people. Clarifying the analysis population, missingness, and completion of both conditions would help readers understand the reach of the outcome summaries.
Finally, the record lists secondary outcomes and describes a mechanistic rationale, but does not provide a statistical plan or results for those secondary measures in the available details. Transparent reporting of prespecified analyses, paired effects, uncertainty intervals, and handling of multiple outcomes would make the evidence easier to evaluate. The absence of those details does not negate the descriptive values; it limits what can be concluded from them.
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 principal limitation of the posted outcome information is the absence of a reported paired treatment-effect estimate. Although means and standard deviations are available for both conditions, the registry does not report participant-level data or the distribution of within-participant differences. The comparative precision and statistical significance of the primary contrast therefore cannot be assessed.
The available counts are not fully reconciled. Enrollment is listed as 9, the study summary says eight healthy, recreationally active males were required, and the outcome entries list 7 in each condition. The registry record does not explain the discrepancy, give reasons for nonparticipation or missing measurements, or identify the analysis population. In a crossover design, it is also not clear whether all listed observations are paired across conditions.
Several design and analysis details are not reported in the registry record, including treatment sequence, washout details, the statistical model, assumptions checks, and any prespecified multiplicity strategy. The summary describes a 4 day glycogen normalization period, while the arm descriptions specify treatment for 5 days; the record does not clarify how these descriptions fit together. It also gives an endpoint timeframe of 8 hours and describes 80-min exercise trials, without explaining their relationship.
The secondary outcomes are named but their results are not available in the posted information. The safety report gives event counts but does not provide event details, timing, relatedness, or a fuller account of the safety population. These limitations constrain interpretation to the descriptive primary outcome and reported event counts; they do not justify assumptions about unreported analyses or procedures.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude — NCT06164665.
- Registry record last updated 2026-03-19; status last verified 2025-05.
- Results first posted 2026-03-19.
- 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.
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19. Record Summary
NCT06164665 is a completed phase 4 randomized, double-blind crossover study sponsored by the United States Army Research Institute of Environmental Medicine. It evaluates pioglitazone versus placebo during steady-state exercise under acute high-altitude exposure. The primary outcome is mean exogenous glucose oxidation in g/min, with a specified timeframe of 8 hours.
The registry reports outcome means of 0.31 for pioglitazone and 0.32 for placebo, with standard deviations of 0.03 and 0.09. The outcome entries list 7 in each condition. A two-arm comparison for this continuous endpoint is marked as missing or not estimable, and no paired effect estimate, confidence interval, or p-value is reported in the registry record.
The record lists concentration of Interleukin-6 and concentration of Serum Hemoglobin as secondary outcomes, but their results are not available in the details. Safety entries report no serious events, 1 other event in the pioglitazone group, and no deaths. Enrollment, eligibility description, and outcome counts differ, and the registry does not explain the discrepancy.