Mars Flavanol Exercise and Cognitive Function Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mars Flavanol Exercise and Cognitive Function Study (NCT01180127), a randomized na study. The primary outcome is CBV-fMRI (Cerebral Blood Volume-functional Magnetic Resonance Imaging).

2. Clinical Question

The registry describes a study of a flavanol-containing food product and aerobic exercise in relation to cognitive function and brain structure. Its listed primary measure is regional cerebral blood volume, an indirect indicator of basal brain metabolism, rather than a direct measure of cognitive performance. Modified Rey Auditory Verbal Learning Test and VO2max are listed as secondary outcomes. Their results are not reported in the registry record.

3. Trial Design

This was a randomized, single-masked, factorial trial with enrollment of 41. The registry lists the phase as not applicable. It names New York State Psychiatric Institute as sponsor and gives the study start as 2009-12 and primary completion as 2013-10; the record status is completed. Who was masked and how masking was maintained are not reported in the registry record.

The factorial arrangement combined two intervention dimensions: a flavanol-containing food product versus a food product lacking flavanol, and aerobic training versus wait list control. The four described combinations were aerobic training with the flavanol-containing product; wait list control with that product; aerobic training with the product lacking flavanol; and wait list control with the product lacking flavanol. The arm descriptions specify a 12-week intervention period.

In general, a factorial design can distinguish the effects associated with each intervention dimension and can also examine whether the dimensions interact. An interaction means that the association with one intervention may differ according to the level of the other intervention. That is a general property of the design, not a statement about the analysis in this trial. Which factorial contrasts were estimated, whether interaction was assessed, and how the randomized groups were handled in analysis are not reported in the registry record.

The record lists four outcome measures and six analyses, but does not provide the analysis methods or results in the registry record for this account. The primary outcome was collected up to 12 weeks after intervention exposure. The timing of secondary outcome assessments and further details of allocation procedures are not reported in the registry record. The record identifies randomized allocation but does not describe sequence generation or concealment.

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

Analysis population for the primary outcome, as defined in the registry: One subject in the exercise, food additive lacking flavanol arm, and one subject in the wait list control food additive without flavanol arm had non useable data for this outcome which is why there are only 8 subjects analyzed in those two arms rather than 9.

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 CBV-fMRI (Cerebral Blood Volume-functional Magnetic Resonance Imaging), measured over Up to 12 weeks after exercise/dietary intervention exposure.

The primary endpoint is CBV-fMRI, expressed as percent cerebral blood volume in a brain region. Cerebral blood volume refers to the amount of blood within a tissue region. The registry describes CBV under steady-state conditions as an indirect measure of basal metabolism in the brain. CBV-fMRI produces maps that represent basal metabolism across brain regions.

This endpoint is therefore a physiological imaging measure. It is not itself a direct test of memory, general cognition, or brain structure. The study title refers to cognitive function and brain structure, while the primary outcome description specifically concerns cerebral blood volume and its relation to basal metabolism. Modified Rey Auditory Verbal Learning Test is listed separately as a secondary outcome, as is VO2max.

The primary outcome timeframe is up to 12 weeks after exposure to the exercise and dietary intervention. The record does not identify a single brain region or a single endpoint comparison for interpretation: it notes that the primary outcome has several categories or time points and was not reduced to one comparison. Specific regional estimates, outcome distributions, and inferential results are not reported in the registry record. Accordingly, the measure's purpose can be explained, but the size and precision of any group differences cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure: percent cerebral blood volume in a brain region. For a continuous outcome, a common summary is the mean, which represents the arithmetic average of observed measurements. The registry identifies the primary outcome parameter as a mean and the measure of dispersion as standard deviation. A standard deviation describes how spread out individual measurements are around their group mean. It is not the same as a standard error or a confidence interval, which describe uncertainty in an estimated quantity.

In general, comparing group means requires both an estimated contrast and a measure of its uncertainty. A confidence interval gives a range of values compatible with the data and the analysis assumptions; a narrower interval indicates greater precision than a wider one. A p-value, when reported, summarizes how compatible the observed data are with a specified null model. Neither a p-value nor a confidence interval alone communicates the full clinical or scientific importance of an effect. The registry record does not report means, standard deviations, contrast estimates, confidence intervals, or p-values for the primary outcome.

How does the factorial allocation affect interpretation?

The four intervention combinations vary two components: food product flavanol content and exercise assignment. In general, factorial analyses can estimate the average association of each component across the levels of the other component, and can test whether the combined pattern departs from what an additive model would suggest. This latter feature is often called an interaction. Such interpretations depend on the contrast definition and analysis model. The registry identifies a factorial model but does not report whether these effects or an interaction were estimated, nor how any model was specified. No particular factorial effect should therefore be attributed to the posted record.

What does the mean and standard deviation tell a reader?

A mean can summarize a group's central value, while the standard deviation describes variability among measurements within that group. When groups are compared, overlap in individual measurements does not by itself determine whether the estimated group contrast is precise. Precision also depends on the number of usable observations and the variability of the measure. General statistical interpretation would use the group summaries together with an uncertainty interval and the stated analysis. Those numerical results and the analysis model are not reported in the registry record.

How should the planned sample-size logic be read?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is framed around detecting a stated fraction of the observed effect. These are assumptions for planning scenarios, not observed power and not evidence that the trial was designed around those assumptions. Numerical sample-size outputs are not reported in the registry record. An effect-based planning illustration also depends on how the observed effect was estimated and should not be mistaken for an independent confirmation of that effect.

In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. It does not describe the probability that a particular observed result is true. Retrospective calculations based on an observed effect can be especially difficult to interpret because the observed estimate is uncertain. The registry does not report a protocol-based sample-size justification, so the planning illustration should not be taken as a description of the trial's original design rationale.

What can be concluded from the analysis record?

The record lists six analyses but does not give their specifications or results. It does not identify whether the analyses were adjusted, whether they accounted for multiple outcome measures or comparisons, or whether model assumptions were checked. For a continuous endpoint, assumptions might concern the distribution of residuals, the variability across groups, and the handling of repeated or region-specific measurements. These are general considerations; the record does not say which methods were applied. Over-dispersion is principally a concern for count outcomes, where variability exceeds what a simple count model expects; it is not a description of the posted continuous CBV-fMRI endpoint.

Randomization supports comparisons between assigned groups when the analysis and follow-up preserve the randomized assignment appropriately. It does not by itself resolve missing measurements, multiple testing, or uncertainty in a small dataset. The record does not report an intention-to-treat analysis, a per-protocol analysis, adjustment for baseline values, or other population and model choices. Consequently, the analysis strategy and the precision of any intervention estimate cannot be reconstructed from the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and six analyses. Multiple outcomes, brain regions, time points, or contrasts can create multiple opportunities to observe a result that appears noteworthy. In general, multiplicity procedures may control the chance of false-positive findings across a defined family of tests, or investigators may identify a prespecified primary comparison. The record does not report a multiplicity adjustment, define a family of tests, or state which analyses were prespecified. It notes that the primary outcome has several categories or time points and was not reduced to one comparison. The specific categories, time points, and corresponding results are not reported in the registry record.

For the primary outcome, the registry says one subject in the aerobic-training arm with the food product lacking flavanol and one subject in the wait-list arm with the product lacking flavanol had non-usable data. It reports 8 subjects analyzed in each of those arms rather than 9. This indicates an outcome-specific reduction in usable observations for these two groups. The handling of the unusable data, including whether any imputation or sensitivity analysis was used, is not reported in the registry record.

Further details on missingness in the other arms, outcome-specific analysis populations, participant exclusions, and missing secondary-outcome data are not reported in the registry record. The record also does not state whether the analysis followed randomized assignment or used another population definition. Without those details and the outcome estimates, the robustness of the results to missing data and multiple comparisons cannot be evaluated.

11. 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 adverse-event figures list zero serious adverse events in each of the four groups: exercise with dietary intervention, 0 among 10 at risk; no exercise with dietary intervention, 0 among 11 at risk; exercise with the food product lacking flavanol, 0 among 10 at risk; and wait list control with the food product without flavanol, 0 among 10 at risk. The registry also lists zero other adverse events in each group, with the same group-specific numbers at risk.

These are recorded event counts, not a comparison of risks or a complete account of all possible events. A zero count in a group means that no event of that recorded category appears in the posted figures; it does not establish that the underlying event risk is zero. The record gives no serious adverse-event terms. Death figures are not reported in the registry record, so they cannot be inferred from the zero adverse-event counts. The figures should be read as safety reporting within the registered groups and not as a conclusion about the primary CBV-fMRI outcome.

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

The registry record describes a randomized study of two intervention components: a flavanol-containing food product and aerobic training. It identifies CBV-fMRI as the primary measure and describes its relation to basal brain metabolism. It also lists a memory assessment and VO2max as secondary outcomes. These details establish the study's question and measurement framework, but they do not supply the outcome estimates needed to judge the observed pattern.

The primary outcome's group means, estimated contrasts, uncertainty intervals, and tests are not reported in the registry record. Thus, the direction and magnitude of any difference between assigned combinations are unknown from this record. There is also no basis for assessing the precision of an estimate or whether it is compatible with a range of possible effects. A trial design and endpoint description cannot stand in for those results.

The record's note about unusable data is relevant to the primary endpoint: it reports 8 analyzed subjects rather than 9 in each of two arms. This may affect the amount of information available for those arm comparisons, but the impact cannot be quantified without the measurements and analysis. The record does not report how missing data were handled or whether findings changed under alternative assumptions.

In general, statistical evidence about an intervention depends on the estimated effect, its uncertainty, the analysis plan, and the context of the comparisons. Those details are not available for the primary or secondary outcomes. The adverse-event counts are separately reported as zero for serious and other events in each group, while deaths are not reported. These counts do not answer the efficacy or physiological-outcome question. The record therefore supports a description of the trial design, endpoints, and recorded adverse-event counts, but not a conclusion about whether the assigned intervention combinations changed CBV-fMRI or the secondary outcomes.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its factorial allocation separates two intervention dimensions rather than treating exercise and the food product as a single inseparable package. In general, such a design can help distinguish component effects and assess whether components act differently in combination. The value of that structure depends on prespecified contrasts and a clearly described analysis, neither of which is reported in the registry record.

The primary measure also illustrates an important distinction between a physiological surrogate and a direct functional outcome. CBV-fMRI is described as an indirect measure of basal metabolism across brain regions. The study also lists a memory measure and VO2max, but the registry does not report results for these measures. A change in one kind of measure would not automatically establish a change in another; each requires its own outcome estimate and interpretation.

The record notes unusable imaging data in two arms, making analysis populations and missing-data handling important to interpretation. It also identifies multiple outcome measures and analyses, which raises general questions about how comparisons were selected and whether multiplicity was addressed. These are not assertions that the analysis was inadequate; the relevant methods are simply not reported in the registry record.

Finally, the absence of outcome estimates limits what can be learned statistically from the record. A completed randomized study can be described in terms of allocation, exposure, and measurement, but inference requires the estimates and uncertainty that connect those elements to the results. The distinction between trial design and reported evidence is central to reading this study accurately.

14. 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 interpretation is that the registry record does not report the primary outcome results. It gives no group means, standard deviations, contrast estimates, confidence intervals, or p-values for CBV-fMRI. The listed secondary outcomes also have no reported results. Effect direction, magnitude, and precision therefore cannot be assessed.

The primary endpoint is described as regional percent cerebral blood volume, but the record notes several categories or time points and does not reduce them to one comparison. It does not identify the specific regions or comparisons needed to interpret a single summary result. Details on image processing, outcome quality criteria beyond the noted unusable data, and model specification are not reported in the registry record.

One participant in each of two arms had non-usable primary-outcome data, leaving 8 subjects analyzed in those arms rather than 9. The record does not explain the missingness mechanism or the method used to handle those observations. It also does not report missing-data information for the other arms or secondary outcomes. Further details about participant characteristics, eligibility criteria, baseline balance, allocation concealment, the identity of those masked, adherence, and withdrawals are not reported in the registry record.

The record lists four outcome measures and six analyses but does not describe the prespecified analysis plan, multiplicity strategy, or analysis populations. The sample-size assumptions are presented as a planning illustration based on an observed effect; a protocol-based design justification is not reported in the registry record. These omissions prevent an assessment of how closely the analyses followed a planned strategy and how robust any findings would be to alternative choices. The adverse-event counts are reported, but death figures are not.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mars Flavanol Exercise and Cognitive Function Study — NCT01180127.
• Registry record last updated 2018-12-05; status last verified 2018-11.
• Results first posted 2015-01-27.
• 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.

18. Record Summary

The registry describes NCT01180127, the Mars Flavanol Exercise and Cognitive Function Study, as a completed randomized, single-masked factorial trial sponsored by New York State Psychiatric Institute. Enrollment was 41; the study started in 2009-12 and primary completion was 2013-10. The trial combined a flavanol-containing or flavanol-lacking food product with aerobic training or wait list control, with arm descriptions specifying 12 weeks.

The primary outcome was CBV-fMRI, measured as percent cerebral blood volume in a brain region up to 12 weeks after intervention exposure. Modified Rey Auditory Verbal Learning Test and VO2max are listed as secondary outcomes. The registry notes unusable primary-outcome data for one participant in each of two arms and reports 8 analyzed subjects rather than 9 in those arms. Primary and secondary outcome results, analysis details, and death figures are not reported in the registry record. Serious and other adverse-event counts are listed as zero in each group.