Whole Body Protein Metabolism of a Whey/EAA Supplement Using Continuous Oral Stable Isotopes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Whole Body Protein Metabolism of a Whey/EAA Supplement Using Continuous Oral Stable Isotopes (NCT04612400), a randomized na study. The primary outcome is Whole-body Protein Net Balance.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked crossover trial sponsored by the University of Arkansas. The registry record lists the condition as healthy and reports 8 participants enrolled. The trial started on 2020-11-04, reached primary completion on 2021-09-06, and is listed as completed. Its phase is recorded as NA.

The two supplement conditions were low dose, described as 6.3g of EAA/whey protein, and high dose, described as 12.6g. The intervention is named oral amino acid tracer and categorized as OTHER. The stated objective was to evaluate a continuous oral sip-feeding stable-isotope tracer method for assessing whole-body protein metabolism in response to those doses. The summary says results would be compared with results previously determined using constant infusion with the same supplement. Those earlier results are not reported in the registry record.

A crossover design generally means that participants receive more than one condition, allowing measurements under different conditions to be compared within a participant. That structure can account for stable differences between participants when an analysis appropriately uses the paired observations. The registry record does not report the treatment sequence, the timing or length of periods, any washout interval, or how the crossover structure was handled in the analysis. Although the trial is listed as randomized and double-masked, details of the randomization method and which parties were masked are not reported in the registry record.

The arm summaries each list 8 observations. These are condition-level counts and should not be interpreted as 8 separate participants in each parallel group: the study is identified as a crossover trial and enrollment was 8. The registry record does not provide a more detailed account of participant flow or the number included in a specific analysis.

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.

Overall Study

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 Whole-body Protein Net Balance, measured over 240 minutes.

The primary endpoint was whole-body protein net balance, reported as a mean in grams over 240 minutes. The registry description says it was determined using stable-isotope ingestion and blood analysis for isotope concentrations. The posted mean was 6.2 for the low-dose condition, with a standard deviation of 5.1, and 11.8 for the high-dose condition, with a standard deviation of 3.9.

Net balance is intended to express the overall balance of protein metabolism rather than only one component of that metabolism. In general, a net-balance measure combines processes that add protein with processes that remove or break it down. Stable-isotope tracer methods can be used to study metabolic processes by tracking labeled molecules through measurements such as blood isotope concentrations. Those are general descriptions; the registry record does not report the detailed calculation or kinetic model used for this specific endpoint.

The endpoint fits the stated methodological question because the trial aimed to evaluate whether continuous oral tracer feeding could assess whole-body protein metabolism under the two supplement conditions. It is a measured metabolic outcome over a defined interval, not a direct measure of long-term health or clinical benefit. The registry record does not report a clinically important threshold for interpreting the magnitude of net balance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

The primary outcome is reported as a mean, the average of the recorded values for a condition. A mean gives a concise account of the observed level of the endpoint, but it does not show every participant’s measurement or how those measurements were distributed. In this trial, the low-dose mean was 6.2 grams per 240 minutes and the high-dose mean was 11.8 grams per 240 minutes. These values describe the posted condition summaries; they do not by themselves provide a test of the difference between conditions.

The reported standard deviation describes the spread of measurements around each mean. The low-dose standard deviation was 5.1 and the high-dose standard deviation was 3.9. In general, a larger standard deviation indicates greater observed dispersion around the mean. It is not a measure of uncertainty in the mean itself, and it should not be read as a range containing a particular proportion of values unless distributional assumptions and supporting information are available. The registry record does not report participant-level values or a distributional assessment.

Why does the crossover design matter?

In general, a crossover design compares conditions within the same participants. This can be useful when participant characteristics that remain stable across conditions contribute to outcome variation, because each participant can serve as their own reference. A suitable analysis must account for the fact that repeated observations from one person are related. Treating the conditions as if they came from unrelated groups can misrepresent the uncertainty.

The record identifies the study as randomized and crossover, but does not describe the order of conditions, period structure, washout, or the statistical model. It also does not post the paired participant-level differences or their standard deviation. Therefore, the condition-level means and standard deviations are not enough to reconstruct a crossover comparison. The registry results list no analysis for the continuous two-arm comparison, and the comparison is described as not estimable from the posted values.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical model and repeated-sampling framework. Its width communicates precision: wider intervals indicate greater uncertainty about the estimated quantity. A confidence interval for a crossover contrast would depend on the within-participant information and the chosen model, not just on the two condition means. No confidence interval for the primary comparison is reported in the registry record. It is therefore not possible to use the posted results to quantify the precision of a condition contrast.

A p-value, when reported, addresses how compatible the data are with a specified null model, conditional on the analysis assumptions. It does not measure the size or clinical importance of an effect, and it is not the probability that a hypothesis is true. No p-value for the primary comparison is posted. The stated reason is that values were missing or not estimable for a two-arm comparison of the continuous endpoint. The absence of a p-value should not be converted into a claim that there was no difference.

Why can dispersion complicate analysis?

In general, over-dispersion means that observed variation is greater than a statistical model assumes. When present, it can make standard errors too small and confidence intervals too narrow if the model does not account for it. The posted endpoint is continuous and its summaries include standard deviations; the registry record does not report an over-dispersion assessment or a model for this outcome. The concept is relevant as a general consideration, but no conclusion about over-dispersion can be drawn from the posted summaries alone.

What do the planning assumptions mean?

The sample-size material describes planning illustrations based on the observed effect, rather than the trial’s original design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the detectable effect is expressed as a stated fraction of the observed effect. These assumptions define hypothetical planning scenarios. Such calculations are not observed power, do not show the probability that the trial detected an effect, and do not replace the results of an analysis.

The registry record does not report the trial’s own sample-size justification or any planned power calculation. It also does not report an analysis plan for the primary outcome, a named statistical test, covariate adjustment, or a strategy for handling period or sequence effects. The posted planning assumptions should therefore be kept separate from the trial’s design rationale and from the descriptive outcome values.

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("Low Dose", "High Dose")
n   <- c(8, 8)
m   <- c(6.2, 11.8)
sp  <- c(5.1, 3.9)
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  Low Dose  8  6.200  5.100  1.936  10.464
CARM  High Dose  8  11.800  3.900  8.540  15.060

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no posted secondary outcomes. It also lists no analyses. A multiplicity strategy for several primary or secondary hypothesis tests is therefore not described in the posted record. In general, multiplicity arises when several inferential tests are conducted and the chance of at least one false-positive result may increase; methods to address it depend on the prespecified testing plan. The record does not report such a plan, so no adjustment or testing hierarchy can be identified.

The primary continuous outcome has condition-level means and standard deviations, but the two-arm comparison is described as not estimable because values were missing or not estimable for that comparison. The registry record does not explain whether the missing information concerns paired data, another component of the analysis, or a different issue. It does not report a missing-data count, reasons for missingness, imputation method, sensitivity analysis, or a comparison of complete-case and other analyses. Those details should not be inferred from the presence of descriptive summaries.

The record does not define an intention-to-treat, per-protocol, or safety population for the primary analysis. It does not provide participant flow by condition or explain which participants contributed to the endpoint summaries. Although 8 participants were enrolled and each condition summary lists 8 observations, the registry record does not give a more detailed analysis-population account. In a crossover trial, the number of observations and the number of participants can have different meanings because participants may contribute measurements under multiple conditions.

In general, a prespecified analysis plan clarifies which participants and measurements are included, how missing data are handled, and how repeated measurements are modeled. No such statistical plan is reported in the registry record. These omissions limit assessment of whether the descriptive results correspond to the intended analysis and how robust any comparison might be.

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.

The adverse-event entries report zero serious adverse events in the low-dose condition, among 8 at risk, and zero in the high-dose condition, among 8 at risk. Other adverse events are also reported as zero in each condition, with 8 at risk in each. Deaths are recorded as zero in both conditions. The registry record lists no top serious-event terms.

These figures describe what was recorded in the registry for the stated at-risk counts. They do not establish that no adverse events could occur, and they should not be read as proof of safety. In general, a study with a small number of participants may be unable to characterize uncommon events reliably. The crossover design also means that condition-level at-risk counts should not automatically be interpreted as separate groups of distinct people; the registry record does not provide a detailed safety-population description.

The record does not provide further details about how adverse events were solicited, coded, graded, or judged related to the intervention. Nor does it describe the duration of safety follow-up. The entries therefore support a narrow statement: no serious events, other events, or deaths are listed for either condition in the posted safety results. They do not support broader conclusions about event rates or comparative safety.

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

The posted results establish that the registry contains descriptive whole-body protein net balance summaries for the two supplement conditions. The low-dose mean was 6.2 grams per 240 minutes, with a standard deviation of 5.1; the high-dose mean was 11.8 grams per 240 minutes, with a standard deviation of 3.9. They also show that the primary outcome was measured using stable-isotope ingestion and blood analysis over 240 minutes, as described in the registry record.

The higher reported mean in the high-dose condition is a descriptive pattern, not a formal finding of a statistically significant difference. No two-arm inferential analysis, confidence interval, or p-value is posted, and the registry record states that values were missing or not estimable for that comparison. Without a crossover analysis that uses the within-participant data, the condition summaries do not show the uncertainty around a paired contrast.

The study’s stated goal was to evaluate the continuous oral sip-feeding tracer method and compare results with those previously determined by constant infusion. The registry record does not report the constant-infusion results or a direct comparison of methods. Therefore, the posted dose-condition summaries do not establish the validity, agreement, or relative performance of oral sip feeding versus constant infusion.

These results are also limited to a metabolic endpoint measured during 240 minutes in a study enrolling 8 healthy participants. They do not establish a long-term outcome, a clinical benefit, or how the findings apply to people or circumstances not described in the record. The registry record does not report a clinically important threshold for the endpoint or a protocol-based sample-size rationale. The appropriate interpretation is consequently bounded: the record gives descriptive measurements under two conditions, while leaving the main inferential and method-comparison questions unresolved in the posted results.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its question concerns not only a supplement condition but also a measurement approach. Continuous oral sip feeding of a stable-isotope tracer was intended to evaluate whole-body protein metabolism, with results to be compared against results previously determined using constant infusion. Questions about measurement methods require attention to how the measurement behaves and how comparisons are analyzed, not only to whether condition means differ.

The crossover structure is relevant because measurements under multiple conditions can be linked within participants. In general, within-person comparisons can remove some variation attributable to stable differences among people, but they require an analysis that preserves the pairing. The registry record identifies a randomized crossover design yet does not post a paired comparison, a confidence interval, or a test for the primary outcome. The distinction between descriptive summaries and an inferential estimate is especially important in that setting.

The posted standard deviations also make visible that individual measurements vary around the condition means. Describing that variability is useful, but it cannot replace an uncertainty estimate for the comparison. Without the within-participant variation, condition-level summaries do not reveal the precision of a crossover contrast.

The record also illustrates the difference between study-planning calculations and a trial’s observed analysis. Planning illustrations based on an observed effect can help readers consider hypothetical sample-size requirements under stated assumptions, but they are not observed power and do not show what the original design intended. The trial’s own sample-size justification is not reported in the registry record.

More broadly, transparent reporting of analysis populations, missing data, paired results, and method-comparison outcomes would help readers evaluate how strongly a measurement study answers its intended question. Those elements are not reported in the posted registry results, so interpretation must remain focused on the available descriptive endpoint summaries.

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 main limitation for statistical interpretation is that the primary outcome is reported descriptively without a two-arm inferential comparison. Although means and standard deviations are available for both conditions, the registry record says that values were missing or not estimable for the comparison. No confidence interval or p-value is reported. As a result, the precision of the condition contrast cannot be assessed from the posted results.

The crossover design creates a further limitation in the available reporting. A valid within-participant comparison depends on paired observations, yet paired differences and their variability are not reported. The registry record also does not describe treatment sequence, periods, washout, or how possible period effects were handled. Without these details, readers cannot assess whether the analysis appropriately reflected the design.

The study enrolled 8 participants, and the registry record does not report its own sample-size justification. The planning illustrations are not a substitute for that rationale and are not observed power. The record also lacks a detailed account of the analysis population, participant flow, missingness, and handling of missing data. These gaps make it difficult to determine exactly which observations contributed to the posted summaries.

The stated objective includes comparison with prior constant-infusion results, but those results and a direct method-comparison analysis are not reported in the registry record. The detailed tracer protocol and the calculation used to derive net balance are also not reported. The endpoint is limited to a 240-minute measurement, and no clinically important threshold is given. Finally, safety reporting is limited to the listed counts; event collection and follow-up details are not reported. These limitations constrain conclusions to the descriptive information recorded for this trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Whole Body Protein Metabolism of a Whey/EAA Supplement Using Continuous Oral Stable Isotopes — NCT04612400.
• Registry record last updated 2023-08-28; status last verified 2022-12.
• Results first posted 2023-08-28.
• 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

NCT04612400 is a completed randomized, double-masked crossover trial sponsored by the University of Arkansas. It enrolled 8 healthy participants, began on 2020-11-04, and reached primary completion on 2021-09-06. The stated objective was to evaluate continuous oral sip feeding of a stable-isotope tracer for assessing whole-body protein metabolism under low- and high-dose EAA/whey supplement conditions.

The primary endpoint was mean whole-body protein net balance in grams over 240 minutes. The low-dose mean was 6.2, with a standard deviation of 5.1; the high-dose mean was 11.8, with a standard deviation of 3.9. No two-arm inferential analysis is posted. The registry record does not report paired comparison results or the earlier constant-infusion results referenced in the study summary.