Molecular Transducers of Physical Activity Consortium (MoTrPAC) - Pediatric Protocol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Molecular Transducers of Physical Activity Consortium (MoTrPAC) - Pediatric Protocol (NCT04151199), a randomized na study. The primary outcome is Cardiopulmonary Exercise Test (CPET) VO2 Peak.

2. Clinical Question

The broader scientific aim was to assess molecular changes in response to physical activity. The pediatric center’s description distinguishes a cross-sectional phase, which measured molecular transducers from blood after an acute exercise challenge, from a mechanistic randomized intervention phase. The primary posted outcome is not itself a molecular-transducer assay: it is CPET VO2 peak, described as a change in log-transformed VO2 peak calculated as L/min.

The cross-sectional high-activity and low-activity groups were included for baseline measures only and did not have follow-up outcomes. The posted comparison of the intervention groups is therefore the relevant comparison for the primary endpoint at baseline and Week 12. The registry identifies the allocation as randomized, but details of the randomization procedure and allocation concealment are not reported in the registry record.

3. Trial Design

NCT04151199 is a randomized, parallel-design study with no masking. Its status is completed, and the registry records enrollment of 318. The study is sponsored by Wake Forest University Health Sciences. The recorded start date is 2019-11-22, and the primary completion date is 2025-05-31. The phase is listed as NA.

The pediatric protocol describes two related phases. In the cross-sectional phase, children and adolescents underwent an acute exercise challenge, with molecular transducers measured from blood. The intervention phase is described as a mechanistic randomized controlled trial: participants recruited from the cross-sectional phase were assigned to endurance exercise training or a no-exercise control for approximately 12 weeks. The registry’s arm descriptions say both intervention groups completed an acute test and biospecimen collection following the intervention period; the control group did not participate in the training intervention.

The registry also identifies two cross-sectional groups, high activity and low activity. Their descriptions say they did not participate in the intervention after a single acute exercise test. The primary endpoint description explicitly notes that these groups were enrolled for baseline measures only and have no follow-up data or outcomes. Thus, they should not be treated as additional intervention comparison groups for the Week 12 result.

The brief study description lists planned group sizes for its phases, while the record separately lists overall enrollment and the posted endpoint has its own group counts. These figures describe different parts of the registry record and are not reconciled there. The intervention comparison is reported for 100 endurance-exercise participants and 39 no-intervention control participants. The reasons for the difference between those posted endpoint counts and other enrollment descriptions 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Only Cross-Sectional HA and Only Cross-Sectional LA groups were only enrolled for baseline measures and do not have follow-up data or outcomes.

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 Cardiopulmonary Exercise Test (CPET) VO2 Peak, measured over Baseline; Week 12.

The primary endpoint is CPET VO2 peak, or peak oxygen uptake measured during a cardiopulmonary exercise test. The registry describes the endpoint as changes in log-transformed CPET VO2 peak calculated as L/min, with measurements at baseline and Week 12. The reported unit is a ratio of geometric means, and the arm-level estimate is presented with a 95% confidence interval.

VO2 peak is used in exercise research as a physiological measure obtained during an exercise test. In general, CPET provides a structured way to assess oxygen uptake during exertion; the endpoint therefore supplies a functional measure alongside the protocol’s broader focus on molecular responses to physical activity. This general description does not establish that a change in the endpoint corresponds to a particular clinical benefit.

Because the outcome is log-transformed and summarized using geometric means, the comparison is expressed as a ratio rather than as a simple difference in arithmetic means. A ratio communicates the relative scale of the modeled group estimates. The registry’s primary endpoint wording specifies the time points and measurement, but further operational details, such as the precise test protocol and any prespecified handling of values outside expected ranges, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a ratio of geometric means convey?

For a continuous outcome analyzed on a logarithmic scale, exponentiating a modeled contrast commonly expresses the comparison as a ratio of geometric means. A ratio is interpreted relative to 1: a ratio of 1 indicates equal values on the ratio scale, while a ratio above or below 1 indicates a relative difference in one direction or the other. The registry identifies the endpoint unit as a ratio of geometric means and reports a between-group mean relative difference of 1.21. This ratio should not be treated as an absolute change in VO2 peak or as a change in L/min.

Log transformation is often used when values are positive and relative changes are of interest, or when the distribution is more suitable for analysis after transformation. That is a general rationale, not a statement about the investigators’ specific reason. The registry says the outcome was log-transformed but does not report diagnostic checks or details of the transformation beyond that description.

How should the confidence intervals be read?

A confidence interval expresses uncertainty around an estimate under the statistical model and its assumptions. Narrower intervals indicate greater precision than wider intervals on the same scale. The posted arm estimates have 95% confidence intervals, whereas the reported between-group relative difference has a 97.5% confidence interval. These intervals apply to different estimates and should be read separately. For a ratio, 1 is the reference value corresponding to no relative difference. The interval from 1.15 to 1.27 lies above that reference.

A confidence interval is not a range containing a fixed proportion of individual participants’ measurements. Nor does it account automatically for every source of uncertainty, such as model misspecification, selection into the analysis, measurement limitations, or multiple testing. The registry does not report enough detail to assess all those issues.

What does the mixed models analysis do?

Mixed models are a general class of methods that can represent both average patterns and dependence among observations. In a study with repeated measurements, measurements from the same participant are generally related, so a model may account for that within-participant association rather than treating each observation as independent. This is a general explanation of the method name. The registry reports a mixed models analysis but does not describe its fixed effects, random effects, covariance structure, adjustment variables, or handling of incomplete repeated measurements. The precise model cannot therefore be reconstructed from the registry record.

The p-value reported for that analysis is p < 0.001. A p-value assesses how compatible the observed data are with a specified null hypothesis under the model. It is not a measure of the probability that the finding is due to chance, and it does not show whether the estimated difference is meaningful in practice. The registry does not give further detail about the exact test statistic or degrees of freedom used.

What is the role of the planning illustrations?

Sample-size illustrations based on an observed effect are planning exercises, not a report of the trial’s original design justification and not observed power. The record’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such illustrations describe how planning requirements would vary under those assumptions. They do not establish that the trial had a particular probability of detecting an effect, and they do not explain how the study’s actual enrollment targets were chosen.

Over-dispersion is a general concern when variation in data is greater than a model’s assumed distribution allows. If it is not accounted for, standard errors may be underestimated and confidence intervals may be too narrow. This concept is not evidence that over-dispersion occurred in this trial. The registry does not report a dispersion parameter or a specific assessment of over-dispersion for the primary endpoint.

More broadly, valid interpretation depends on the analysis population, missing-data assumptions, model specification, and endpoint measurement. Randomization supports a comparative design, but it does not by itself answer whether every randomized participant was included in the analysis or whether missing outcomes could have influenced the estimate. Those details are not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a mixed models analysis with p < 0.001, together with a between-group mean relative difference of 1.21 and a 97.5% confidence interval from 1.15 to 1.27. Those are the reported inferential results and should take precedence over any simple unadjusted calculation if the two disagree. The record does not flag a discrepancy.

A separate unadjusted re-calculation is not reported in the registry record. The posted endpoint is log-transformed and the summary statistics are expressed as geometric-mean ratios, while the sponsor’s analysis uses mixed models. An unadjusted calculation from summary statistics would not reproduce the full mixed-model analysis, particularly without the model specification and participant-level repeated measurements. It should not be presented as an alternative estimate of the sponsor’s analysis.

The arm estimates are useful for understanding the scale and direction of the posted result, but they do not supply the missing details of the model or explain exactly how the reported between-group estimate was obtained. The registry does not report an independent replication of the analysis or further model diagnostics.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and 12 analyses. Four secondary outcomes are named: HDL-C, LDL-C, triglycerides, and HbA1C. The record does not describe a multiplicity adjustment, a hierarchy among outcomes, or which analyses were designated confirmatory versus exploratory. When multiple outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase; adjustment or prespecified prioritization can address that concern in some settings. This is a general statistical issue, not evidence that the reported primary result is invalid.

The primary endpoint description identifies baseline and Week 12 and notes that the cross-sectional high-activity and low-activity groups had baseline measures only. This clarifies that those groups did not contribute follow-up outcomes as described in the record. However, the analysis populations for the intervention comparison are not fully defined. The registry does not state whether the primary analysis followed intention-to-treat principles, whether participants were analyzed as randomized, or whether a per-protocol or other population was used.

Missing-data methods are not reported in the registry record. In particular, the record does not explain how missing Week 12 measurements were handled, whether missingness was assessed by arm, or what assumptions were used for any model-based treatment of incomplete outcomes. The posted group counts alone do not identify why a participant may be absent from an analysis, and they should not be interpreted as evidence of withdrawal or missing data without further information.

The record also does not provide a protocol-based statistical analysis plan, details of interim analyses, or a sample-size justification. The planning illustrations based on the observed effect are not a substitute for those design details. Without those elements, the extent to which all analysis choices were prespecified cannot be assessed from the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event record lists 0 serious adverse events in each of the four groups. The numbers at risk for serious adverse events are 65 in the only cross-sectional high-activity group, 114 in the only cross-sectional low-activity group, 100 in the endurance-exercise group, and 39 in the no-intervention control group. The registry also records 0 deaths in each group.

For other adverse events, the record lists 2 affected participants among 65 at risk in the cross-sectional high-activity group, 16 among 114 in the cross-sectional low-activity group, 59 among 100 in the endurance-exercise group, and 11 among 39 in the no-intervention control group. These are counts of affected participants as recorded, not estimates of comparative risk adjusted for follow-up time or other factors. No serious adverse event terms are listed.

These figures should be read as registry-recorded event counts rather than proof that no serious events occurred outside the recorded observation and reporting process. The record does not provide event timing, severity details for other events, attribution to the intervention, exposure duration by participant, or statistical comparisons. The cross-sectional groups also differ in their role from the randomized intervention groups. The counts alone therefore do not support a causal safety comparison between arms.

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

The posted result indicates that the endurance-exercise group had a higher modeled CPET VO2 peak estimate relative to the no-intervention control group on the reported ratio scale. The between-group estimate is 1.21, with a 97.5% confidence interval of 1.15 to 1.27, and the mixed models analysis reports p < 0.001. The estimate is statistically distinguishable from 1 under the reported analysis, while the interval conveys the uncertainty around the relative comparison.

This finding does not, by itself, establish the clinical importance of the difference. The registry does not provide a threshold for a clinically meaningful change in CPET VO2 peak, nor does it link the endpoint result to a health outcome. A statistically detectable relative difference and a clinically important benefit are distinct claims. No medical advice follows from the statistical result.

The result also does not establish that every child or adolescent would have the same response, or that the estimate applies to populations beyond the study participants. The registry record does not provide the demographic and clinical details needed to evaluate representativeness. Nor does this primary endpoint result answer the protocol’s broader molecular research questions: those require interpretation of the relevant molecular outcomes, which are not presented in this primary comparison.

Finally, the estimate is tied to the described intervention, comparator, endpoint, and follow-up period. It should not be generalized to other exercise programs, durations, or settings without evidence. The registry describes an approximately 12-week intervention in its study summary and records baseline and Week 12 for the primary endpoint. Statistical significance should be read alongside the confidence interval, the analysis limitations, and the distinction between a physiological measure and a clinical outcome.

14. Why This Trial Matters Statistically

This trial is statistically informative because it separates a cross-sectional exercise challenge from a randomized intervention comparison. The distinction matters: the cross-sectional high-activity and low-activity groups contribute baseline information, while the posted primary comparison concerns endurance exercise and no-intervention control at baseline and Week 12. Treating these as one analysis would blur different study questions and follow-up structures.

The endpoint is reported on a ratio scale after log transformation, and the inferential result comes from a mixed models analysis. Together, these features make clear why interpretation should focus on the model-based relative comparison rather than on a difference between raw arm estimates. They also show why arm summaries alone cannot reproduce the sponsor’s repeated-measures analysis.

The registry further illustrates the importance of distinguishing the statistical signal from its practical meaning. The reported confidence interval and p-value describe evidence and precision under the analysis; they do not define a clinically important threshold. Safety counts likewise need context about attribution, exposure, and event timing before they can be used for comparative conclusions.

Finally, registry records can contain multiple enrollment descriptions, outcome measures, and analyses that require careful separation. Here, the overall enrollment, phase descriptions, and endpoint-specific group counts are not fully reconciled in the record. Recognizing that limitation prevents planning descriptions or baseline-only groups from being mistaken for the randomized follow-up comparison.

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.

Several trial-specific details needed for a full assessment are not reported in the registry record. Although allocation is listed as randomized, the sequence-generation method and allocation concealment are not described. Masking is listed as none; the record does not explain whether outcome assessors or laboratory personnel were masked. The mixed models analysis is named, but its exact specification and adjustment variables are absent.

The record contains multiple enrollment descriptions: overall enrollment is 318, while the brief summary describes a cross-sectional phase and planned intervention groups with different counts. The posted primary comparison includes 100 participants in the endurance-exercise group and 39 in control. The record does not reconcile these figures or explain how they relate to the enrolled population. This limits assessment of participant flow and the analysis population.

Missing-data handling, adherence, intervention fidelity, and reasons for any differences in group counts are not reported. The registry also does not give a clinically meaningful threshold for CPET VO2 peak, detailed endpoint measurement procedures, or the rationale for the 97.5% confidence interval on the relative difference. Multiplicity procedures and the prespecified status of the analyses are not described.

The record lists completed status, but the timing and completeness of each outcome’s reporting cannot be judged from the primary result alone. The two baseline-only cross-sectional groups cannot inform the Week 12 intervention comparison. Finally, adverse-event counts are reported without attribution, timing, or comparative analysis, so they have limited value for determining whether events were related to the intervention.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Molecular Transducers of Physical Activity Consortium (MoTrPAC) - Pediatric Protocol — NCT04151199.
• Registry record last updated 2026-07-14; status last verified 2025-05.
• Results first posted 2026-07-14.
• 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

NCT04151199, the MoTrPAC Pediatric Protocol, is a randomized, parallel, unmasked study with phase listed as NA and status listed as completed. Wake Forest University Health Sciences is the sponsor. The registry records enrollment of 318, a start date of 2019-11-22, and a primary completion date of 2025-05-31.

The pediatric study description includes a cross-sectional acute exercise phase and a mechanistic randomized intervention phase. The posted primary endpoint is CPET VO2 peak at baseline and Week 12. The reported between-group mean relative difference is 1.21, with a 97.5% confidence interval of 1.15 to 1.27; the mixed models analysis reports p < 0.001. Detailed model specifications, missing-data methods, and multiplicity procedures are not reported in the registry record.