Effect of Number of Remote Limb Ischemic Conditioning Cycles on Learning Enhancement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Number of Remote Limb Ischemic Conditioning Cycles on Learning Enhancement (NCT03512041), a randomized phase 1 study. The primary outcome is Balance Score.

2. Clinical Question

The clinical question is a learning question in healthy young adults, not a question about treating a disease. The primary measure is the change in time spent maintaining a stability platform near horizontal during repeated trials. The registry description interprets a greater increase in balance score as more learning over the course of the study.

The comparison is among four groups: RLIC with 5 cycles, RLIC with 4 cycles, RLIC with 3 cycles, and sham conditioning. This makes the primary analysis an across-group comparison rather than a single direct comparison of one RLIC schedule against sham. The question is whether the group means are compatible with a common value or whether the posted results indicate evidence of differences among them.

The registry also lists balance training, arm training, and sequence production training among the interventions, but the primary outcome results reported for this analysis are for the four groups named above. How those additional listed interventions relate to participants’ study activities is not reported in the registry record. The result therefore addresses the recorded balance-score outcome and these four conditioning groups, not every listed intervention or other forms of learning.

3. Trial Design

The registry classifies this as a randomized, single-masked, parallel-group Phase 1 study, with an enrollment of 40. The record names Washington University School of Medicine as sponsor and gives the status as completed. The study start is listed as 2016-12-13 and primary completion as 2018-02-13.

Four groups contribute to the reported primary balance-score analysis. The RLIC groups received 5, 4, or 3 cycles; the comparator group received sham conditioning. The arm descriptions specify cuff inflation on the non-dominant arm. For the 5-cycle RLIC group, the description gives 45 minutes of conditioning; for the 4-cycle group, it gives 35 minutes; and for the 3-cycle group, it gives 25 minutes. Sham conditioning is described as lasting 45 minutes. The RLIC inflation pressure is described relative to systolic blood pressure, while the sham pressure is described relative to diastolic blood pressure.

Randomization supports a planned comparison among groups, but the method used to generate the allocation sequence, any stratification, and the concealment process are not reported in the registry record. “Single” masking is the registry’s classification; which study roles were masked is not reported in the registry record. The record identifies a parallel model, but does not report further detail about visit scheduling or adherence.

The primary outcome is described as a change from Visit 1 to Visit 7, with the timeframe listed as approximately 1 week. The arm-level results give a mean change and standard deviation for each group. Participant-level data, analysis-population definitions, and details of missing outcome handling are not reported in the registry record. The study also lists balance, arm, and sequence production training interventions, but their relation to the reported primary comparison is not specified 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

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 Balance Score, measured over Visit 1 and Visit 7, approximately 1 week.

The primary endpoint is the change in balance score from Visit 1 to Visit 7. The score is the average amount of time, in seconds, that a participant maintains a stability platform within ±3° of horizontal during 5 trials of 30 seconds each. The registry describes the outcome as a mean and reports standard deviations for the group summaries.

This endpoint is used as a behavioral measure of learning in the study. The registry’s interpretation is that a greater increase in score over the study period means more learning occurred. Measuring change across visits focuses on improvement during the study rather than only the final balance performance. The reported summaries therefore describe the average change for each conditioning group, alongside the amount of variation among participants.

The endpoint is specific to performance on this stability-platform task. It does not directly measure every aspect of learning, and the registry record does not report an independent validation or a threshold for a meaningful change. It also does not report participant-level measurements or confidence intervals for the group means. The group summaries can describe the direction and variability of the observed changes, while the reported ANOVA addresses whether the group means differ overall. Neither form of summary, on its own, establishes why any differences occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a change in seconds, summarized as a mean and standard deviation. The registry’s reported inferential method is ANOVA across the 5-cycle RLIC, 4-cycle RLIC, 3-cycle RLIC, and sham-conditioning groups. The reported p-value for that analysis is 0.172. No test statistic, degrees of freedom, confidence interval, or adjusted group estimates are reported in the registry record.

What does the ANOVA address?

General statistical context: ANOVA evaluates an overall hypothesis about group means. In this setting, the overall test concerns whether the mean balance-score changes can be treated as equal across the four groups, given the model’s assumptions. A result that does not reach a conventional significance threshold does not prove equality. It means the analysis did not provide sufficiently strong evidence against the equal-means hypothesis under the test used.

An overall test does not identify which groups might differ, nor does it provide the size of a specific contrast. Pairwise comparisons would answer narrower questions, such as how the 4-cycle RLIC group compares with sham conditioning. The registry record does not report such estimates or their confidence intervals. The record also does not report any planned contrast, adjustment for multiple comparisons, or post-hoc procedure. Therefore, the overall p-value should not be used as if it were a set of separate tests for each RLIC schedule.

How should the group summaries be read?

The reported arm values are means for change in balance score, and the accompanying spreads are standard deviations. A mean describes the average observed change in a group. A standard deviation describes how dispersed participant changes were around that group mean; it is not the standard error and is not a confidence interval. The record gives no interval estimates for the means. The standard deviations help show that individual responses varied, but do not by themselves give a direct estimate of the uncertainty in a group comparison.

General statistical context: uncertainty in a comparison depends on the within-group variability and the number of observations contributing to each group, as well as the chosen analysis. Confidence intervals are useful because they describe a range of effect estimates compatible with the data and analysis, rather than giving only a significance test. No confidence interval for the overall effect or a specific comparison is reported in the registry record.

What assumptions matter for a continuous-outcome ANOVA?

General statistical context: a conventional ANOVA relies on assumptions about independent observations and the distribution and variability of outcomes within groups. The registry record identifies the method as ANOVA but does not report diagnostics, transformations, robust alternatives, or details of how the model was specified. It is therefore not possible to assess from the record whether assumptions were checked or how departures from assumptions were handled.

Over-dispersion is most often discussed for count outcomes: it means that observed variation is greater than a model expects, which can make standard errors too small and tests too optimistic if ignored. That concept is not directly the central issue for this continuous balance-score endpoint. For continuous outcomes, unequal variances or unusual distributional patterns may instead affect the performance of a conventional ANOVA; the registry record does not report checks for these features.

What can recalculation establish?

Simple unadjusted recalculations from group-level means, standard deviations, and sample sizes can provide exploratory pairwise comparisons, but they do not reproduce analyses that depend on participant-level data, covariate adjustment, or other model details. In this record, the available data do not yield estimable values for two-arm comparisons of the continuous endpoint. Consequently, no recalculated pairwise estimate or interval can be interpreted alongside the reported omnibus test. The registry record does not provide participant-level data or a more detailed analysis specification that would support a fuller reconstruction.

The sample-size assumptions describe a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration asks what sample size might be needed to detect an effect set as a fraction of the observed effect under those assumptions. It is not an estimate of the probability that this completed trial detected an effect, and it is not the trial’s own design justification. The registry record does not report the protocol’s sample-size rationale or a target effect used to plan enrollment.

These methods distinctions matter for interpretation. The reported p-value is an omnibus test result; the arm means and standard deviations are descriptive summaries; and any planning illustration is conditional on assumptions. None should be substituted for an unreported pairwise effect estimate with a confidence interval. The registry record also does not report an analysis plan detailed enough to establish how outcome distributions, missing observations, multiplicity, or analysis populations were handled.

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("RLIC - 5 Cycles", "RLIC - 4 Cycles", "RLIC - 3 Cycles", "Sham Conditioning")
n   <- c(10, 10, 11, 9)
m   <- c(9.9, 11.5, 7, 11.3)
sp  <- c(4.6, 5.7, 5.1, 4.6)
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  RLIC - 5 Cycles  10  9.900  4.600  6.609  13.191
CARM  RLIC - 4 Cycles  10  11.500  5.700  7.422  15.578
CARM  RLIC - 3 Cycles  11  7.000  5.100  3.574  10.426
CARM  Sham Conditioning  9  11.300  4.600  7.764  14.836

11. Analyses Reported by the Sponsor

The sponsor’s reported analysis is an ANOVA comparing the four groups on the primary balance-score change. Its p-value is 0.172. The record does not report an estimated overall contrast or confidence interval, and it does not give pairwise estimates for the individual RLIC schedules compared with sham conditioning.

The recalculation material for two-arm comparisons cannot provide estimable values for this continuous endpoint from the posted summary statistics. It therefore does not offer a separate pairwise result to set against the sponsor’s omnibus analysis. The group means and standard deviations remain useful descriptions, but they are not themselves a replacement for the reported ANOVA or a formal pairwise analysis.

No discrepancy is flagged between a sponsor analysis and a recalculation. Where a sponsor’s own analysis and a simple unadjusted recalculation conflict, the sponsor’s analysis takes precedence because it may reflect the trial’s specified analysis and information unavailable in arm-level summaries. Here, the main interpretive limit is that the registry reports an overall test without the group contrasts and uncertainty intervals that would show the magnitude and precision of specific comparisons.

The record does not report whether the ANOVA was adjusted for covariates, whether assumptions were assessed, or whether the analysis was prespecified. Those details should not be inferred from the method label alone.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 3 analyses, while the posted results identify the balance score as the primary outcome. The record reports an ANOVA for the four-group primary comparison. It does not report the analysis results for secondary outcomes; the number of secondary outcomes with posted results is 0. The record does not describe a multiplicity strategy, such as an adjustment across outcomes or across planned group comparisons.

General statistical context: when several outcomes or contrasts are tested, the chance of at least one apparently unusual result can increase if each is judged separately at the same threshold. Prespecified priorities and an adjustment plan can clarify how such evidence should be interpreted. Because the registry record does not report a multiplicity plan, it is not possible to determine whether the reported test was part of a broader family of analyses or how any such family was addressed.

Missing-data information is also limited. The record does not report how many participants contributed to the primary outcome at each visit, whether any observations were missing, how missing measurements were handled, or whether any sensitivity analyses were conducted. The group sizes in the posted results are stated, but the analysis population and participant flow are not described in the information available for this outcome. It should not be assumed that every enrolled participant completed every visit or contributed to every analysis.

The registry record does not report an intention-to-treat definition, a per-protocol definition, exclusions from analysis, or rules for handling protocol deviations. It also does not report whether the primary endpoint was analyzed using change scores, an adjustment for baseline values, or another model beyond identifying ANOVA as the method. These omissions limit assessment of the analysis choices and of the robustness of the result.

These gaps do not invalidate the posted numbers, but they constrain what can be concluded from them. The omnibus result is interpretable as the reported test, while broader claims about a complete outcome family, missing observations, or a prespecified analysis strategy cannot be supported from the registry record.

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’s adverse-event figures report 0 serious adverse events in each of the four groups: RLIC with 5 cycles, RLIC with 4 cycles, RLIC with 3 cycles, and sham conditioning. The corresponding numbers at risk were 10, 10, 11, and 9. The record also reports 0 other adverse events in each group, with those same group sizes at risk, and 0 deaths in each group.

These figures mean that no affected participants were recorded in the adverse-event categories shown in the registry results. They do not establish that no symptoms or events of any kind occurred, and they do not establish that the groups have identical safety profiles. The record does not list serious adverse-event terms, and the top serious-event terms list is empty. Further definitions of the event collection period, event ascertainment, or coding are not reported in the registry record.

General statistical context: when no events are recorded in a group, the underlying event risk is not known to be zero. Rare events may not appear in a study of this size, and the ability to compare event rates depends on the amount of follow-up and the completeness of event collection. Those details are not reported for the safety results. The adverse-event counts should therefore be read as the events recorded in this trial, not as proof that an intervention has no safety risks.

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

The posted results describe average improvement on a stability-platform task among healthy young adults assigned to three RLIC cycle schedules or sham conditioning. The group means were 9.9 seconds for 5-cycle RLIC, 11.5 seconds for 4-cycle RLIC, 7.0 seconds for 3-cycle RLIC, and 11.3 seconds for sham conditioning. The standard deviations show variation in participant changes within each group. The reported omnibus ANOVA had p = 0.172.

What the result does mean is that the registry reports no statistically significant overall evidence of different mean balance-score changes across the four groups in this analysis. What it does not mean is that all group means are exactly equal, that the interventions are equivalent, or that differences of practical importance have been ruled out. No confidence interval or pairwise estimate is reported to show which differences remain compatible with the data or how precisely those differences were estimated.

The endpoint reflects learning on a specific balance task, over the study timeframe described as approximately 1 week. The result does not directly establish effects on other learning tasks, people with health conditions, longer-term outcomes, or outcomes not reported in the registry record. The study’s population is described as healthy young adults, so conclusions should remain tied to that population and the recorded behavioral measure.

Nor does the result establish a mechanism. The registry describes the intervention and the task, but the posted analysis does not show why group means might differ or why they might be similar. Randomization is a design feature intended to support group comparisons; incomplete reporting of allocation procedures, analysis populations, and missing-data handling leaves important details about execution and analysis uncertain.

The most restrained reading is descriptive: the group averages varied, but the reported overall test did not provide strong evidence of a difference among them. Because precision intervals and specific contrasts are not reported, the result cannot distinguish confidently between no meaningful differences and differences that the study did not estimate precisely enough to identify.

15. Why This Trial Matters Statistically

This trial is statistically interesting because the question concerns the number of conditioning cycles, not simply whether conditioning was used. The four-group structure compares three RLIC schedules with a sham condition, making the primary reported result an omnibus comparison across several groups. That design highlights a common interpretive distinction: an overall test can address whether group means differ somewhere, but it does not tell readers which specific schedules differ or by how much.

The group summaries make the value of uncertainty reporting clear. The means are not identical, but their interpretation depends on participant-level variability, group sizes, and the precision of the contrasts. Standard deviations describe variation in outcomes, while confidence intervals for group contrasts would directly communicate uncertainty about differences. Such intervals are not reported in the registry record.

The trial also illustrates why a non-significant result should not be translated into equivalence. A p-value of 0.172 does not show that the conditioning schedules produce the same balance learning, and the record does not report an equivalence margin or a non-inferiority framework. Without a prespecified range of differences considered negligible and an analysis designed to test that question, equality is not established.

Finally, the gap between an omnibus result and specific estimates matters for practical interpretation. Readers may want to know whether different cycle counts are associated with different mean changes, but the reported analysis does not give those pairwise estimates or their precision. A complete statistical account would also clarify the planned analysis, missing-data handling, multiplicity, and participant flow. The registry record’s concise results permit a careful description of the outcome and overall test, while leaving those broader questions unresolved.

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.

The trial enrolled 40 participants, distributed across four primary-outcome groups with 10 in the 5-cycle RLIC group, 10 in the 4-cycle group, 11 in the 3-cycle group, and 9 in the sham group. These group sizes are modest, and the record does not report a sample-size justification tied to a clinically or behaviorally meaningful difference. Consequently, the ability to identify differences of a particular size cannot be assessed from the registry record.

The primary result is reported as an omnibus ANOVA with p = 0.172. The record does not provide a confidence interval, test statistic, degrees of freedom, or adjusted estimates. Pairwise comparisons between RLIC schedules and sham conditioning are not reported, and recalculated two-arm values are not estimable from the posted summary statistics. This restricts interpretation of the magnitude and precision of specific contrasts.

Several design and analysis details are not reported in the registry record: the randomization procedure, the roles masked, whether the primary analysis was prespecified, model details beyond ANOVA, diagnostic checks, analysis-population definitions, participant flow, missing-outcome handling, and sensitivity analyses. The record also does not explain how the additional listed training interventions relate to the primary comparison. These omissions limit assessment of potential bias and reproducibility.

The outcome is a task-specific measure of balance performance, and the recorded population is healthy young adults. The registry record does not report a threshold for meaningful change or evidence that the measure represents broader learning outcomes. The study timeframe is approximately 1 week, so the result does not describe longer-term performance. Secondary results are not posted, and no multiplicity plan is reported.

Safety results show no recorded serious or other adverse events and no deaths in the groups, but the event definitions and ascertainment period are not reported. The absence of recorded events should not be interpreted as evidence that rare events cannot occur. These limitations mean that the most defensible interpretation is confined to the reported short-term balance-score summaries and the overall statistical test.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Effect of Number of Remote Limb Ischemic Conditioning Cycles on Learning Enhancement — NCT03512041.
• Registry record last updated 2019-08-26; status last verified 2019-08.
• Results first posted 2019-08-26.
• 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

NCT03512041 is a completed randomized, single-masked, parallel-group Phase 1 study sponsored by Washington University School of Medicine. It enrolled 40 healthy young adults and examined whether the number of remote limb ischemic conditioning cycles was associated with learning enhancement. The primary outcome was change in balance score from Visit 1 to Visit 7, described as approximately 1 week.

The reported groups were RLIC with 5 cycles, RLIC with 4 cycles, RLIC with 3 cycles, and sham conditioning. Their mean changes were 9.9, 11.5, 7.0, and 11.3 seconds, respectively. The reported overall ANOVA had p = 0.172. The registry does not report pairwise estimates or confidence intervals for the group comparisons, and secondary outcome results are not posted.

The adverse-event results report 0 serious adverse events, 0 other adverse events, and 0 deaths in each group. Details of the analysis population, missing-data handling, multiplicity plan, and sample-size justification are not reported in the registry record.