Effect of Educational Booklet for Foot-related Exercises for Prevention and Treatment in People With Diabetic Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Educational Booklet for Foot-related Exercises for Prevention and Treatment in People With Diabetic Neuropathy (NCT04008745), a randomized na study. The primary outcome is Change From Baseline Diabetic Neuropathy Symptoms at 8-weeks.

2. Clinical Question

The trial’s stated objective was to investigate the effect of a foot-related exercise educational booklet on diabetic neuropathy status, functional outcomes, and gait biomechanics. Its primary outcome was the change from baseline in MNSI symptoms at 8-weeks. The record also lists secondary outcomes covering gait kinematics and kinetics, dynamic plantar pressure distribution, tactile and vibration sensitivity, foot health and functionality, foot isometric strength, and functional balance.

The outcome is a between-group comparison of recorded means, not a description of what happened to every participant. The MNSI scale description states that the total score ranges from 0 to 13, with 13 representing the worst rating of neuropathy. However, the posted primary result is labelled as a change from baseline, and the registry record does not provide baseline group values or a fuller account of how the change values were derived. The result therefore needs to be read as the reported comparison of the recorded endpoint, rather than as a complete account of symptom trajectories.

3. Trial Design

The registry describes NCT04008745 as a randomized, double-masked, parallel-group trial. It was conducted under the title Effect of Educational Booklet for Foot-related Exercises for Prevention and Treatment in People With Diabetic Neuropathy, with an official title identifying it as the FOotCAre (FOCAtrial-II) randomized controlled trial. The sponsor was University of Sao Paulo General Hospital. The listed phase is NA, and the status is completed.

The registry records enrollment of 50. The intervention group and control group each have posted outcome results for 25 participants. The intervention was educational and home-based physical therapy by foot-related exercises. The group description says participants were to perform the booklet exercises at home three times/week and follow the project schedule through the end of the 16-weeks study period. The control group did not receive a specific trial intervention in addition to treatment recommended by the health professionals team, including pharmacological treatment, self-care recommendations, and foot care by international consensus.

The trial’s recorded start date is 2019-05-01, and its primary completion date is 2021-05-01. The principal outcome was change from baseline in diabetic neuropathy symptoms at 8-weeks. Listed secondary outcomes include gait kinematics and kinetics, dynamic plantar pressure distribution during gait, tactile and vibration sensitivity, foot health and functionality, foot isometric strength, and functional balance. The registry lists 20 outcome measures and 16 posted secondary outcomes.

Although the record identifies randomization and double masking, it does not describe the randomization procedure, allocation concealment, or who was masked. The registry record also does not report the original sample-size justification, the detailed statistical analysis plan, or the analysis populations. These omissions limit how fully the design and analysis can be assessed from the record alone. The results should therefore be interpreted alongside the information actually documented, rather than assumptions about trial procedures that are not described.

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 Change From Baseline Diabetic Neuropathy Symptoms at 8-weeks, measured over 8-weeks.

The primary endpoint is change from baseline in diabetic neuropathy symptoms at 8-weeks, measured with the Michigan Neuropathy Screening Instrument. The registry describes the MNSI as a questionnaire administered by the participant, with 15 questions about symptoms and events related to leg and foot sensitivity. Responses are summed to form a total score ranging from 0 to 13; the record states that 13 represents the worst rating of neuropathy.

A symptom questionnaire offers a structured way to quantify participants’ reported experiences, allowing a continuous score to be compared between randomized groups. In general, continuous endpoints preserve the amount of variation in scores rather than reducing the outcome to categories such as improved or not improved. A change-from-baseline endpoint is intended to represent movement from an initial assessment, but interpretation depends on how change was calculated and on the baseline data. Those details are not reported in the registry record.

The posted primary means are 5.3 for the intervention group and 6.2 for the control group. The reported mean difference for intervention versus control is -0.9. These figures describe the recorded endpoint at the stated follow-up; they do not by themselves show individual responses, the distribution of changes, or whether any particular participant experienced a meaningful change. Nor does the scale description alone establish a threshold for clinical importance. The registry record does not report such a threshold.

7. Results Posted in the Registry

• Intervention Group: mean 5.30 versus 6.20 on control; difference -0.90 (95% CI -1.21 to -0.59), standardized effect d = -1.63; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline of the Foot and Ankle Kinematics During Gait at 8-weeks

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 23.70 versus 22.70 on control; difference 1.00 (95% CI 0.56 to 1.44), standardized effect d = 1.25; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Intervention Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline of the Foot and Ankle Kinetics During Gait at 8-weeks

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 1.30 versus 1.20 on control; difference 0.10 (95% CI 0.04 to 0.16), standardized effect d = 1.00; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Intervention Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline Dynamic Plantar Pressure Distribution During Gait at 8-weeks

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Intervention Group: mean 338.20 versus 402.40 on control; difference -64.20 (95% CI -75.36 to -53.04), standardized effect d = -3.19; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Intervention Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcome set spans several related aspects of foot and lower-limb function: gait kinematics and kinetics, plantar pressure, tactile and vibration sensitivity, foot health and functionality, isometric strength, and functional balance. This breadth reflects the trial objective, which extends beyond symptom scores to functional outcomes and gait biomechanics. A pattern across such measures could help describe whether numerical differences appear across related domains, but the registry record lists no reported analyses for the secondary outcomes.

Three secondary outcomes have posted arm summaries and calculated comparisons in the results used for interpretation: gait kinematics, gait kinetics, and dynamic plantar pressure distribution. Their reported unadjusted mean differences are respectively 1.0 degrees, 0.1 N*m/kg, and -64.2 kPa, each with an unadjusted p-value of <0.001. These numerical contrasts should be read in the units and directions recorded for their respective outcomes. They do not establish a common clinical direction, because the measures describe different constructs and the record does not provide clinical thresholds or direction conventions for interpreting the changes.

The primary endpoint concerns change in neuropathy symptoms, while these secondary measures concern mechanics and pressure during gait. They may be related to the trial’s broader research question, but they are not interchangeable with the symptom score. A secondary pattern can offer context for the primary result; it cannot independently confirm the primary finding or establish a mechanism. The registry reports 16 posted secondary outcomes, yet the detailed analysis population, prespecification, and multiplicity strategy are not reported in the registry record.

Unadjusted secondary results carry less weight as confirmatory evidence when many outcomes are examined. In general, testing many outcomes increases the chance that some results will look statistically notable by chance alone. Adjustments or a prespecified hierarchy can address that concern, but the registry record does not report whether such procedures were used. The secondary figures are therefore best regarded as descriptive signals requiring cautious interpretation, rather than as a set of independent confirmations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline of the Foot and Ankle Kinematics During Gait at 8-weeks
• Change From Baseline of the Foot and Ankle Kinetics During Gait at 8-weeks
• Change From Baseline Dynamic Plantar Pressure Distribution During Gait at 8-weeks
• Change From Baseline Tactile Sensitivity at 8-weeks
• Change From Baseline Vibration Sensitivity at 8-weeks
• Change From Baseline Foot Health and Functionality at 8-weeks
• Change From Baseline Foot Isometric Strength at 8-weeks
• Change From Baseline Functional Balance at 8-weeks

9. Statistical Interpretation

10. Statistical Methods Explained

The primary result is a comparison of means for a continuous endpoint. A continuous measure can take values across a scale, rather than belonging only to a small set of categories. The registry describes the MNSI total score as ranging from 0 to 13, and describes the endpoint as change from baseline at 8-weeks. Reporting a mean gives the average recorded value within a group. It does not describe the complete distribution, the most common value, or the range of individual experiences.

What does the mean difference represent?

The reported mean difference is intervention minus control. The intervention group’s posted mean is 5.3 and the control group’s mean is 6.2; the reported mean difference is -0.9. The minus sign indicates that the recorded intervention-group mean is lower than the control-group mean under this contrast definition. Since the endpoint is labelled change from baseline and the registry does not provide a fuller change-score convention, the sign should not be given a clinical interpretation beyond that numerical comparison.

A mean difference retains the original units of the measure. Here, the endpoint unit is listed as units on a scale. This makes the contrast interpretable on the instrument’s scale, although a statistically detectable difference is not automatically a clinically important difference. The record does not report a threshold that would identify a meaningful change for participants.

How should the confidence interval be read?

A confidence interval gives a range of estimates compatible with the observed data and the statistical method used, under that method’s assumptions. It communicates uncertainty around the estimated mean difference: a narrower interval indicates greater precision, while a wider interval indicates less precision. The interval for the primary contrast lies below zero. That placement is consistent with the reported unadjusted p-value of <0.001 for a test against no mean difference. The interval does not show the probability that the true effect falls inside it, nor does it account for sources of uncertainty that the calculation did not model.

The registry reports group standard deviations of 0.5 for intervention and 0.6 for control. A standard deviation describes how dispersed individual measurements are around the group mean. It is not the same as the uncertainty in the estimated mean, and it is not itself a confidence interval. The posted comparison also includes a standardized effect-size value, but that value is a scale-free summary and should not replace the mean difference in the instrument’s units.

What does the p-value tell the reader?

The p-value is reported as unadjusted and is <0.001. In general, a p-value describes how compatible the data are with a specified null model, assuming the model and its conditions hold. A small p-value is not the probability that the null hypothesis is true, and it does not quantify clinical importance. The registry record does not report a multiplicity adjustment for the set of outcome measures, so the primary p-value should be read as the posted unadjusted result rather than as evidence corrected across all outcomes.

The calculated comparisons are simple unadjusted re-calculations from posted summary statistics. Such calculations do not incorporate covariates, participant-level values, or any adjustment that may have been used in a sponsor analysis. The registry record lists no reported analyses for the secondary measures. Accordingly, these comparisons are descriptive statistical summaries of posted group results, not a replacement for an unreported analysis plan or participant-level analysis.

Why can variation and study design affect interpretation?

Group means can be influenced by variation within each arm, the precision of measurement, and the number of participants contributing data. Randomized allocation is intended to create groups that are comparable on average, but in a small study chance imbalances can remain. Baseline results and participant-level details would help assess the context of the observed follow-up values; those details are not reported in the registry record.

In general, over-dispersion means that the observed variability is greater than a statistical model assumes. When that occurs, methods that underestimate variability can produce confidence intervals that are too narrow and p-values that are too small. The posted continuous outcome summaries use means and standard deviations, and the recalculated comparison uses those summary statistics. The registry record does not provide enough detail to assess model diagnostics or any alternative variance method used by the sponsor.

Interpretation also depends on complete outcome ascertainment and on who was included in the analysis. The registry record does not report how missing observations were treated, whether all randomized participants were analyzed in their assigned groups, or whether outcome analyses used another population. Those details matter because exclusions or missingness related to outcomes can alter the comparison. Thus, the reported estimates are best understood as the posted summary results, with the analysis and missing-data details that are not reported remaining unresolved.

11. Confidence Intervals and Precision

The primary mean difference is -0.9, and its confidence interval lies entirely below zero. This indicates that the posted estimate is not centered on no difference and that the interval, under the calculation used, excludes zero. The interval’s role is to show estimation uncertainty, not to guarantee that the true contrast lies within its limits or to measure the chance of a clinically important effect.

The reported group standard deviations are 0.5 in the intervention group and 0.6 in the control group. These summarize the spread of individual observations around their respective means. They should not be interpreted as uncertainty around the difference itself. The confidence interval is the relevant posted summary of precision for the estimated group contrast.

Precision is conditional on the information and method used to calculate the interval. The registry provides group summaries and a recalculated unadjusted comparison, but does not provide participant-level data or report the full analysis method. It also does not describe missing-data handling, covariate adjustment, or analysis populations. These omissions prevent a broader assessment of whether the interval captures all important sources of uncertainty.

The interval’s separation from zero is a statistical feature, not a clinical threshold. The registry record does not state how large a change on this endpoint would be considered important to participants or clinicians. Nor does it report baseline means that would help contextualize the magnitude of the change. Accordingly, the interval supports a precise description of the estimated contrast under the posted calculation, but does not establish clinical importance, durability beyond the specified follow-up, or applicability to other populations.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are illustrations derived from the observed effect, not the trial’s original design assumptions. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect to detect is set at a stated fraction of the observed effect. For these continuous outcomes, the displayed counts are participants per arm, not total participants across the trial and not total events.

The 80% power column gives the illustrative number of participants per arm that the calculation estimates would be needed for an 80% chance of detecting the chosen effect under the planning assumptions, if that effect and those assumptions were correct. The 90% power column uses a higher target chance of detecting the same chosen effect, so it generally calls for more participants per arm. These are design-planning concepts, not guarantees about what a future study would find.

The rows consider planning for 100%, 75%, and 50% of the observed effect. Smaller assumed effects need more participants because a subtler group difference is harder to distinguish from random variation. This relationship is why planning around the full observed effect can yield smaller illustrative requirements than planning around a fraction of it. The observed effect may be uncertain, especially when estimated from a small trial, so treating it as a dependable future target can be misleading.

These figures are not observed power. They do not describe the probability that the completed trial detected an effect after the result was known. The registry record does not report the trial’s original sample-size justification, so the displayed planning assumptions should not be mistaken for the rationale used to enroll participants. They are only illustrations based on the posted effect and stated calculation conditions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.900; pooled standard deviation σ = 0.552.
2. n = 2 × (1.96 + 0.842)² × 0.552² / -0.900² = 5.9, rounded up to 6 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.9                      # observed difference in means
sigma <- 0.552268050859363                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4008745)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 75% of observed effect: n per arm = 11 (80% power), 15 (90% power)
 50% of observed effect: n per arm = 24 (80% power), 32 (90% power)
power.t.test: 7 
Simulated power at n = 6 per arm: 0.723 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The record lists 20 outcome measures, including a primary symptom endpoint and multiple secondary measures of gait, sensitivity, foot health, strength, and balance. When many outcomes are assessed, the chance of observing at least one apparently notable result by chance can rise. This is the general multiplicity problem. Researchers may address it through a prespecified outcome hierarchy, adjusted significance thresholds, or other methods, but the registry record does not report a multiplicity strategy or a detailed statistical analysis plan.

The primary result is accompanied by an unadjusted p-value of <0.001. That is the posted value for its comparison; it should not be read as adjusted for the set of outcomes. The secondary outcomes also have unadjusted recalculated comparisons where posted summary statistics permit them. Their numerical results are more exploratory when the relationship among tests and any correction procedure are not documented. The record does not report whether secondary hypotheses were prespecified or which, if any, were intended as confirmatory.

Missing-data handling is another unresolved issue. The results list 25 participants in each arm for the primary outcome, but the registry record does not explain whether those counts represent all randomized participants, whether any outcomes were unavailable, or how missing values were handled. It does not report imputation procedures, sensitivity analyses, or reasons for missing observations. Without these details, it is not possible to judge whether missingness could have affected the estimated comparisons.

The registry record also does not report the analysis population, such as whether participants were analyzed according to randomized assignment or whether a different population was used. This matters because excluding participants or analyzing them outside their assigned groups can affect the protection randomization is intended to provide. Nor does the record describe interim analyses, covariate adjustment, or the original sample-size justification. These gaps do not alter the posted arithmetic, but they limit assessment of how the estimates were generated and how robust they are to analytical choices.

These uncertainties are reasons for restraint rather than evidence that the results are invalid. They identify information that would be useful for evaluating multiplicity, missingness, and analysis choices. The posted findings can be described as recorded, while the unreported methods should remain unresolved rather than inferred.

15. 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 zero serious adverse events affecting participants at risk in the intervention group and zero in the control group. It also reports zero other adverse events affecting participants at risk in both groups, and zero deaths in each group. These are the safety counts recorded for this trial.

A count of zero means that no events of the specified category were recorded in the registry results for the participants at risk as listed. It does not establish that the intervention has no safety risks, or that no unrecorded or unreported events occurred. The record does not provide event descriptions, severity definitions, follow-up details for adverse events, or information about how events were collected and attributed.

Safety counts are most informative when considered alongside the duration and completeness of monitoring, participant exposure, and definitions used. The intervention description gives a home exercise schedule through the 16-weeks study period, but detailed adverse-event monitoring methods are not reported in the registry record. The posted figures therefore describe the recorded event counts, not a definitive comparison of safety across settings or populations.

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

The primary posted result is a mean difference of -0.9 between the intervention and control groups for change from baseline in MNSI symptoms at 8-weeks. The intervention group’s reported mean is 5.3 and the control group’s is 6.2. The confidence interval lies entirely below zero, and the unadjusted p-value is <0.001. Together, these statistics describe a group-level difference in the recorded endpoint under the calculation used.

That finding does not by itself establish the clinical importance of the difference. The registry record does not report a minimally important difference or another threshold that would indicate what change participants would notice or value. It also does not provide baseline group values or explain the change-score convention in detail. Although the MNSI description says a higher total score represents a worse neuropathy rating, the primary result is labelled as change from baseline. The safe interpretation is therefore to report the numerical contrast as posted without asserting what it means for symptom improvement.

The result is not a statement about every participant. Group means can conceal a range of individual outcomes, and the registry does not give participant-level data or the distribution of changes. A statistically detectable difference does not guarantee that every person responds similarly, nor does it predict what an individual’s outcome would be.

The trial evaluated a particular booklet-and-exercise approach in people with diabetic neuropathy, alongside the usual care described for the control group. The record does not establish whether the result applies to different exercise programs, populations, clinical settings, or follow-up periods. The primary assessment was at 8-weeks, while the intervention schedule is described through 16-weeks; the record does not provide a primary result at the end of that longer schedule.

Finally, the registry’s randomized, double-masked design is relevant, but procedural details and analysis methods are incomplete. Missing-data handling, analysis population, and multiplicity procedures are not reported. These gaps limit certainty about the broader interpretation without changing what the posted summary statistics say. The result should be viewed as evidence of the recorded comparison in this completed trial, not as a universal conclusion or a recommendation about care.

17. Why This Trial Matters Statistically

This trial is statistically interesting because it places a participant-reported symptom measure beside a wider group of functional and biomechanical outcomes. The primary MNSI result addresses symptoms, while gait, plantar pressure, sensitivity, strength, and balance outcomes address other dimensions of foot-related function. Separating these domains matters: a difference in one measure does not automatically imply a difference in another or explain how a participant experiences daily life.

The registry’s randomized, parallel-group structure is intended to support a comparison between the booklet-and-exercise approach and the control care described in the record. The posted primary result includes a mean difference, confidence interval, and unadjusted p-value, allowing readers to consider both the estimated contrast and its statistical precision. This is more informative than a p-value alone, while still requiring attention to endpoint meaning, analysis assumptions, and clinical relevance.

The trial also illustrates why statistical significance and practical importance are separate questions. The primary comparison is statistically distinct from zero according to the posted interval and p-value, but the registry does not state a threshold for meaningful change. Nor does it provide enough detail to evaluate all analysis choices, missing observations, or the interpretation of change scores. The secondary results add breadth but involve multiple outcomes and are not accompanied by reported analyses or multiplicity methods.

Finally, the sample-size planning illustrations help show how a future study’s requirements depend on the effect it aims to detect. They are based on the observed effect rather than on the original trial design rationale, which is not reported. This distinction is important when small studies produce estimates that may be uncertain. Overall, the record supports careful statistical reading: identify the endpoint, examine the contrast and its precision, distinguish primary from secondary evidence, and keep unreported design and analysis details open rather than filling them in.

18. 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 registry record leaves several trial-specific limitations unresolved. It identifies randomization and double masking but does not describe how allocation was generated or concealed, who was masked, or how masking was maintained. These details are important for judging the practical implementation of the design, and should not be inferred from the labels alone.

The primary endpoint is described as change from baseline, but baseline group values and a detailed definition of the change calculation are not reported in the registry record. This makes it harder to assess starting comparability and interpret the direction and magnitude of the recorded change. The record also does not give a clinical threshold for meaningful change on the MNSI, so statistical evidence cannot be translated into a claim about practical importance.

The original sample-size justification and detailed analysis plan are not reported. The planning illustrations based on the observed effect do not answer why the trial enrolled its participants or establish the assumptions used at design. The record does not report missing-data procedures, analysis populations, covariate adjustments, interim analyses, or multiplicity methods. These omissions limit assessment of robustness and confirmatory status.

Although the record lists 16 posted secondary outcomes, it does not list reported analyses for them. The secondary summaries that permit recalculation are unadjusted, and the record does not establish how the outcomes were prioritized. This makes the secondary pattern useful for description but less definitive for inference. The safety results record zero events in the listed categories, but monitoring procedures and event definitions are not described.

Finally, outcome follow-up and the intervention schedule should not be conflated: the primary outcome is stated at 8-weeks, while the intervention group description refers to a schedule through 16-weeks. The registry record does not provide a primary endpoint result at the end of that schedule. These limitations constrain interpretation of duration, generalizability, and the completeness of the trial’s analytical record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect of Educational Booklet for Foot-related Exercises for Prevention and Treatment in People With Diabetic Neuropathy — NCT04008745.
• Registry record last updated 2024-09-19; status last verified 2024-05.
• Results first posted 2024-09-19.
• 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.

22. Record Summary

NCT04008745 is a completed randomized, double-masked, parallel-group trial sponsored by University of Sao Paulo General Hospital. It enrolled 50 people with diabetic neuropathy and compared an educational booklet with home-based foot-related exercises against the care described for the control group.

The primary outcome was change from baseline in MNSI symptoms at 8-weeks. The intervention-group mean was 5.3 and the control-group mean was 6.2; the reported mean difference was -0.9, with an unadjusted p-value of <0.001. The confidence interval lies below zero. The record lists secondary outcomes spanning gait, foot pressure, sensitivity, foot function, strength, and balance, but does not report secondary analyses.

The registry records zero serious adverse events, zero other adverse events, and zero deaths in each group. Details on the original sample-size rationale, analysis plan, missing-data handling, analysis populations, and multiplicity procedures are not reported in the registry record.