Effect of Aging on Cortical Excitability and Motor Learning: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Aging on Cortical Excitability and Motor Learning (NCT03750903), a randomized na study. The primary outcome is Magnetic Resonance Spectroscopy.

2. Clinical Question

The study’s stated objective concerns aging-related changes in GABAergic cortical inhibition and motor performance, as well as whether aerobic exercise may improve inhibitory function and facilitate motor learning. The posted primary outcome is a spectroscopy measure, rather than a direct measure of motor performance. The registry record does not report a separate primary motor-learning performance outcome.

The question is therefore about the measured change in a brain spectroscopy outcome across the intervention period and the statistical evidence reported for comparing the randomized groups. The outcome summaries and the ANOVA result can describe the posted data, but the registry does not provide enough detail to establish exactly how the analysis handled the measurements at both time points.

3. Trial Design

The study is registered as randomized, with a parallel model and no masking. It is marked completed. The phase is recorded as NA, and the condition is aging. The sponsor is the VA Office of Research and Development. The registry lists enrollment of 30; the primary-outcome record separately describes follow-up noncompletion and gives the arm-level outcome counts.

The two behavioral conditions were Aerobic Exercise and Stretching and Balance Training. The aerobic program met thrice weekly for 12 weeks. The comparator condition also met thrice weekly for 12 weeks. The registry describes the latter as a balance and stretching comparator. It does not report further information about how sessions were delivered, whether adherence was assessed, or whether participants received other study activities.

The study began on 2019-03-04, and primary completion is recorded as 2023-09-30. These dates describe the registry record; they do not establish the timing of each participant’s assessments. The primary outcome timeframe is stated as baseline and 12 weeks.

For the primary outcome, the registry reports n=8 in each arm. It also states that 4 participants in the Aerobic Exercise group and 10 participants in the Stretching and Balance Training group did not complete the 12 week follow-up assessment. Reasons for noncompletion and the relationship between the follow-up note and the analyzed outcome counts are not reported in the registry record. The record does not describe the randomization procedure, allocation concealment, or any procedures used to limit bias in measurement or 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

Analysis population for the primary outcome, as defined in the registry: 4 participants in the Aerobic exercise group and 10 participants in the Stretching and Balance Training group did not complete the 12 week follow up assessment

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 Magnetic Resonance Spectroscopy, measured over Baseline and12 weeks.

The primary outcome is titled Magnetic Resonance Spectroscopy and is measured in ppm. Its description specifies measurement of changes in dynamic magnetic resonance spectroscopy of the primary motor cortex during motor learning. The timeframe is baseline and 12 weeks. The outcome is treated as continuous, and the registry reports a mean and standard deviation for each arm.

In general, a continuous outcome can retain information about the range of measured values rather than reducing observations to categories. A mean describes the group’s average value; a standard deviation describes the spread of observed values around that average. Those summaries help characterize the arm-level results, but they do not show the full distribution or establish the precision of a between-arm comparison.

The registry’s stated study objective includes cortical inhibition and motor learning. Magnetic resonance spectroscopy is the posted primary measure for tracking the specified dynamic brain signal during motor learning. The record does not provide a detailed rationale for selecting this endpoint, define a clinically meaningful change, or explain how the spectroscopy signal maps to motor performance. It also does not report a separate measure of learning performance as a primary outcome.

The arm summaries are 0.41 with standard deviation 0.69 for Aerobic Exercise and -0.29 with standard deviation 0.66 for Stretching and Balance Training. These are descriptive summaries. The record does not report a confidence interval for either arm or for their comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the outcome as continuous, with the parameter set to mean and dispersion set to standard deviation. It also reports an ANOVA for the comparison of the two groups and gives p=0.05. The record does not identify a more specific ANOVA form or provide its test statistic, degrees of freedom, or model terms.

What does a mean describe?

In general, the mean is the arithmetic average of the observed values in a group. It summarizes the central level of a continuous measure, but it does not show whether values are clustered near that average or spread widely. Here, the arm means are 0.41 for Aerobic Exercise and -0.29 for Stretching and Balance Training. The outcome unit is ppm. The record does not give the underlying participant-level measurements, so the shape of either group’s distribution cannot be assessed from the means alone.

What does a standard deviation describe?

In general, the standard deviation describes the amount of spread around the mean in the observations. It is not the standard error of the mean and does not itself give a confidence interval. The registry reports standard deviations of 0.69 and 0.66 for the two arms. Similar-looking standard deviations do not establish that the groups have identical variability, and they do not supply a formal comparison of variability.

What does ANOVA test?

In general, analysis of variance evaluates whether observed group means are compatible with a null model in which the relevant population means do not differ, given the chosen model and assumptions. Its p-value is calculated relative to that model. The registry’s p-value is 0.05. Because the record does not describe the model in detail, it is not possible to determine whether the ANOVA compared change scores, incorporated repeated measurements, or used another specification. The outcome timeframe mentions baseline and 12 weeks, but that alone does not identify the analysis method.

General ANOVA assumptions can include appropriate independence or modeling of dependence, a suitable representation of residual variability, and a model appropriate to the outcome and study design. If repeated measurements from the same participant are analyzed, their dependence generally needs to be handled by the analysis. These are general statistical considerations, not reported details of this trial’s analysis. The registry record does not state which diagnostics or adjustments, if any, were used.

Why is an effect estimate with an interval useful?

In general, a between-group effect estimate expresses the magnitude and direction of a comparison in a defined scale. A confidence interval gives a range of values compatible with the data and the estimation procedure, under its assumptions. The interval communicates precision in a way that a p-value alone cannot. The registry does not report a numerical effect estimate or confidence interval for the comparison. The arm means are descriptive and do not, by themselves, provide the uncertainty around a between-arm contrast.

How should the p-value be read?

In general, a p-value is calculated assuming a null hypothesis and a statistical model. It is not the probability that the observed result happened by chance, and it does not give the probability that an intervention is effective. The value 0.05 does not reveal the size of the observed contrast. Its interpretation depends on the analysis plan, model, data quality, and whether other analyses were conducted. The registry does not state a prespecified significance threshold or provide sufficient analysis detail to reconstruct the test.

What do planning illustrations mean?

In general, sample-size planning calculations explore how many participants per arm might be needed under specified assumptions about an effect, significance level, allocation, and statistical approximation. They are planning illustrations, not evidence about the probability that a completed study detected an effect. The stated assumptions describe illustrations based on the observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such calculations depend on those assumptions and do not replace the trial’s actual design rationale. The registry record does not report the trial’s sample-size justification. No planning calculation should be interpreted as observed power.

Why does missing information matter?

In general, missing outcome data can reduce precision and can also introduce bias if missingness is related to participant characteristics or outcomes. The registry says 4 participants in the Aerobic Exercise group and 10 in the Stretching and Balance Training group did not complete the follow-up assessment, while the outcome summaries report n=8 in each arm. It does not state the reasons for missing follow-up, the method used to handle missing values, or the analysis population. No particular missing-data assumption or correction can therefore be attributed to the reported analysis.

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("Aerobic Exercise", "Stretching and Balance Training")
n   <- c(8, 8)
m   <- c(0.41, -0.29)
sp  <- c(0.69, 0.66)
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  Aerobic Exercise  8  0.410  0.690  -0.167  0.987
CARM  Stretching and Balance Training  8  -0.290  0.660  -0.842  0.262

11. Analyses Reported by the Sponsor

The registry reports an ANOVA for the primary outcome comparison, with p=0.05. It does not report a numerical ANOVA effect estimate, a confidence interval, or the test statistic and degrees of freedom. The sponsor’s reported analysis therefore supplies a p-value but not enough detail to quantify the precision of a between-arm effect from that analysis.

A recalculated comparison from posted summary statistics is not reported because the record identifies the two-arm continuous comparison as not estimable from the available information. The arm means and standard deviations can be described, but they do not supply all the information needed for a reliable reconstruction of the sponsor’s test. The reported p-value should not be replaced by an invented or incomplete recalculation.

The registry does not flag a discrepancy between its reported analysis and a recalculation. The record also does not provide enough methodological detail to verify the sponsor analysis independently or to determine exactly how baseline and 12 week measurements entered the ANOVA. The reported p-value should therefore be understood as the analysis result recorded in the registry, with those reporting limits in mind.

12. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome measure and one reported analysis. It posts no secondary outcome measures. This describes the results record; it does not establish that no other outcomes or analyses were planned, collected, or conducted. The record does not report a multiplicity strategy, such as whether or how the analysis accounted for testing multiple outcomes, time points, or alternative models. With no stated analysis plan, the scope of any adjustment cannot be assessed.

Missing follow-up is explicitly noted for the primary outcome. The record says that 4 participants in the Aerobic Exercise group and 10 participants in the Stretching and Balance Training group did not complete the 12 week follow-up assessment. The corresponding arm-level outcome summaries report n=8 in each group. Reasons for noncompletion, timing of withdrawal, and availability of partial measurements are not reported in the registry record.

The registry does not describe whether the primary analysis used all randomized participants, only participants with measured outcomes, or another analysis population. It also does not report imputation, a missing-data model, sensitivity analyses, or assumptions about why measurements were missing. Those details matter because results based on observed follow-up values can be affected when missingness is related to outcomes or participant characteristics. This is a general concern; the record does not establish that such bias occurred.

Without the analysis population and missing-data procedures, it is not possible to establish from the record how the reported ANOVA handled incomplete follow-up or whether its result would be sensitive to alternative assumptions. The reported group counts should be read as the outcome counts recorded for the arm summaries, not as proof of a particular analysis strategy.

13. 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 registry reports serious adverse event figures separately for the two groups. For Aerobic Exercise, 12 were at risk and 0 had a serious adverse event; for Stretching and Balance Training, 18 were at risk and 0 had a serious adverse event. The record also gives 0 deaths in each group. No serious adverse event terms are listed.

These figures describe the events recorded in the registry for the stated groups. A count of zero means no serious adverse events were reported in that group in this record; it does not establish that the intervention is free of risk. The record does not describe the duration or completeness of adverse-event monitoring, event definitions, or how events were collected and assessed. It also does not provide enough information to compare safety statistically.

The at-risk counts used in the adverse-event record are distinct from the arm-level counts reported for the primary outcome. The primary outcome record notes follow-up noncompletion, while the safety record reports its own at-risk figures. Those denominators should not be treated as interchangeable without further information about the analysis and follow-up populations.

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

The results establish what the registry records: arm-level means and standard deviations for a continuous spectroscopy outcome, an ANOVA p-value, and counts of participants who did not complete the 12 week follow-up assessment. The observed mean is 0.41 in the Aerobic Exercise arm and -0.29 in the Stretching and Balance Training arm. The reported p-value is 0.05. These registry entries describe the posted outcome summaries and analysis; they do not, on their own, establish the size or precision of a causal effect.

The result does not show how closely the measured spectroscopy signal corresponds to motor learning performance or to a clinically meaningful change. The registry’s study objective refers to cortical inhibition and motor learning, but the record does not define a threshold for meaningful change or provide a separate primary motor-performance outcome. It also does not report a confidence interval for the between-arm comparison.

The absence of reported secondary outcomes and the limited detail about analysis methods restrict interpretation. The registry does not specify how the two time points were modeled, how missing follow-up was handled, or whether the reported analysis followed a prespecified statistical plan. The note about follow-up noncompletion and the arm-level outcome counts should be considered when judging how representative the summaries may be.

In general, a p-value is not a measure of clinical importance, and an observed group mean is not enough to establish precision. The record does not support a claim that aerobic exercise does or does not improve motor learning or cortical inhibition. It supports a narrower account: the registry reports the stated outcome summaries and ANOVA p-value, with important details about the analysis and missing data not reported.

15. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a reported p-value and a fully interpretable treatment contrast. The registry gives arm-level means, standard deviations, outcome counts, and an ANOVA p-value. It does not give the numerical between-arm effect estimate or its confidence interval. Readers can see the direction of the arm means, but cannot determine the precision of the contrast from those summaries alone.

The outcome is described at baseline and 12 weeks, but the record does not explain how those measurements were represented in the ANOVA. That distinction matters in general because analyses of repeated measurements need to account for their within-participant relationship. A p-value without the model specification is difficult to evaluate or reproduce.

Follow-up completion also deserves attention. The record reports different numbers of noncompleters by group and outcome summaries with n=8 in each arm. It does not explain reasons for missing assessments or the strategy used to address them. This creates uncertainty about the analysis population and the possible influence of missing data.

Finally, the registry posts no secondary outcomes and does not describe a multiplicity plan. This makes it important to avoid treating the reported p-value as a complete account of the study’s evidence. Clear reporting of the estimand, analysis population, missing-data handling, model specification, and effect estimate with uncertainty would make the statistical result easier to assess and reproduce.

16. 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 limitations specific to this record restrict interpretation. The primary outcome description identifies dynamic magnetic resonance spectroscopy of the primary motor cortex during motor learning, but does not provide a detailed measurement protocol, define the direction of a favorable change, or state what magnitude would be meaningful. The relationship between this endpoint and motor-learning performance is not specified.

The timeframe is baseline and 12 weeks, yet the record does not say whether the analysis compared change from baseline, modeled follow-up values with baseline adjustment, or used a repeated-measures approach. The reported ANOVA lacks a model specification, test statistic, and degrees of freedom. No between-arm effect estimate or confidence interval is reported.

The record notes that 4 participants in the Aerobic Exercise group and 10 in the Stretching and Balance Training group did not complete the 12 week follow-up assessment. It does not report reasons, missing-data methods, the analysis population, or sensitivity analyses. The outcome summaries report n=8 in each arm, but the registry does not explain the full relationship between those counts and the follow-up noncompletion note.

The registry also does not report the randomization method, allocation concealment, adherence, or the details of the statistical analysis plan. It posts one primary outcome and no secondary outcome measures, but does not state whether additional analyses were performed or how multiplicity was handled. These are reporting limitations; the record does not establish that any particular bias or analysis problem occurred.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Effect of Aging on Cortical Excitability and Motor Learning — NCT03750903.
• Registry record last updated 2025-04-03; status last verified 2025-04.
• Results first posted 2025-04-03.
• 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.

20. Record Summary

NCT03750903 is a completed randomized, unmasked, parallel study of Aerobic Exercise versus Stretching and Balance Training in the context of aging. Both behavioral conditions met thrice weekly for 12 weeks. The primary outcome is magnetic resonance spectroscopy of the primary motor cortex during motor learning, measured in ppm at baseline and 12 weeks.

The registry reports n=8 in each arm, means of 0.41 and -0.29, standard deviations of 0.69 and 0.66, and an ANOVA p-value of 0.05. It notes that 4 Aerobic Exercise participants and 10 Stretching and Balance Training participants did not complete the 12 week follow-up assessment. A between-arm effect estimate, confidence interval, detailed model specification, and missing-data method are not reported in the registry record.