Effect of Cocoa Supplementation Peripheral and Autonomic Diabetic Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Cocoa Supplementation Peripheral and Autonomic Diabetic Neuropathy (NCT05247034), a randomized na study. The primary outcome is Toronto Clinical Scoring System (TCSS).

2. Clinical Question

The clinical question is whether the TCSS measurement differed over the treatment period between the randomized intervention and control groups. The scale combines assessments of symptoms, reflexes, and sensory tests. Its total score ranges from 0 to 19, with higher values indicating greater neuropathy severity. The registry record specifies change from baseline as the final measurement minus the baseline measurement.

The record identifies the trial as completed and reports enrollment of 39. It does not report a single primary-outcome comparison or the numerical group results needed to describe the size, direction, or precision of any difference. Consequently, the clinical question can be described from the design and endpoint definition, but the available record details do not establish what the outcome data showed.

3. Trial Design

This was a randomized, triple-masked, parallel-group clinical trial sponsored by Anahuac University. The registry lists the phase as not applicable. Enrollment was 39, and the study status is completed. The listed start date is 2021-06-04, and the primary completion date is 2024-06-30. The registry record does not describe the randomization sequence or allocation-concealment procedure.

The intervention group received a diet for patients with diabetes together with four cocoa powder capsules daily, each containing 500 mg, for 12 weeks. The control group received the same stated dietary context together with four methylcellulose capsules daily, each containing 500 mg, for 12 weeks. The registry describes methylcellulose as the control intervention. Further details about adherence assessment, changes in assigned treatment, or other co-interventions are not reported in the registry record.

Triple masking indicates that the record characterizes the trial as masked at three levels, but it does not identify which roles were masked. The identities of those parties and the procedures used to maintain masking are not reported in the registry record. The parallel design means that participants were assigned to a study group and followed within that group rather than being described as crossing between treatments; additional protocol detail is not reported.

The primary outcome was the TCSS at baseline and after 12 weeks. The registry also lists secondary outcomes including rate-dependent depression of the H-reflex, the BEST Questionnaire, the Bristol Stool Form Scale, weight, waist circumference, waist-to-height ratio, abdominal circumference, and systolic blood pressure. The record lists 18 outcome measures and 55 analyses. Those counts indicate that the registry contains a broad set of outcome and analysis entries, but the statistical plan governing them is not reported.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: We could not obtain the Toronto Clinical Scoring System from one subject in the intervention group. Intention-to-treat analysis was performed.

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 Toronto Clinical Scoring System (TCSS), measured over At baseline and after 12 weeks.

The primary endpoint is the Toronto Clinical Scoring System (TCSS), a researcher-administered clinical assessment intended to identify peripheral neuropathy. The score incorporates symptomatology, reflexes, and sensory tests. The registry reports the total score, described as the sum of all units on the scale, rather than a set of separate severity grades.

The score ranges from 0 to 19 points, and higher scores indicate greater severity. The registry explicitly notes that no grades were established based on neuropathy severity. This makes the TCSS a continuous score for the purpose of the stated analysis, rather than a set of categories with defined severity labels.

The outcome was specified at baseline and after 12 weeks. The registry defines the change-from-baseline value as the final measurement minus the baseline measurement. A negative change therefore represents a lower measured score at the final assessment than at baseline, while a positive change represents a higher score. This is an interpretation of the scale direction and change definition, not a statement about the trial’s observed results.

A clinical score can capture several features of a condition in one measure, which may be useful when the research question concerns a combined clinical assessment. Its meaning depends on how consistently the underlying examination is performed and on the interpretation of changes in the score. The registry record does not report measurement reliability, a threshold for a clinically important change, or a severity category system. Numerical primary-outcome results are not reported in the registry record in a single comparison that permits an estimate of the group difference and its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, triple-masked, and parallel-group. Randomization is a design method intended to assign participants to study groups by chance. In general, this can reduce systematic differences between groups at assignment, although it does not guarantee that every characteristic is balanced in a trial. The registry record does not describe the randomization method, sequence generation, or concealment process, so those procedures cannot be evaluated from the record.

Masking is intended to limit the influence of knowledge about assigned treatment on behavior, outcome assessment, or analysis. The record labels the study triple-masked but does not say which participant, clinician, assessor, or other role was masked, or how masking was maintained. The designation can be reported, but the specific protections it represents are not reported in the registry record.

The parallel-group structure assigns participants to a study arm for the trial’s treatment period. The stated comparison is cocoa capsules against methylcellulose capsules, with both groups following a diet for patients with diabetes. Each regimen was specified for 12 weeks. The record does not report the adherence method or whether deviations from the assigned regimen occurred.

What does the mean and standard deviation describe?

The primary outcome is described as a continuous measure summarized by a mean and standard deviation. In general, the mean describes the arithmetic center of a set of measurements. The standard deviation describes how spread out individual measurements are around that mean. These are different kinds of information: a mean gives a central value, while a standard deviation characterizes variability among measurements. Neither alone quantifies the uncertainty in a comparison between groups.

For a treatment comparison, the estimated difference between group means is commonly accompanied by a confidence interval. In general, a confidence interval expresses the precision of an estimate under the statistical model used: narrower intervals indicate greater precision than wider intervals. The registry record’s primary-outcome comparison and its uncertainty are not reported in a single result in the registry record for this analysis, so no interval can be interpreted.

How should change from baseline be read?

The registry defines change from baseline at Week 12 as the final measurement minus the baseline measurement. For the TCSS, higher scores indicate greater severity. Read together, those definitions mean that a negative change corresponds to a lower final score than the baseline score, whereas a positive change corresponds to a higher final score. This definition describes the arithmetic direction; it does not state whether a change is clinically important or whether one group changed more than the other.

In general, a comparison of change scores asks how much the outcome moved from its starting value in each group and then contrasts those movements. Another analysis may compare final values while accounting for baseline measurements. These approaches can differ in their assumptions and precision. The registry record does not report enough detail to identify a complete primary statistical model or to determine which adjustment, if any, was used.

Why do variability and distribution matter?

For a continuous outcome, observed values may vary across participants, and the shape of their distribution can affect the suitability of a statistical model. In general, the mean and standard deviation summarize central tendency and spread but do not reveal all features of a distribution, such as skewness or unusual values. A model’s assumptions and diagnostic checks therefore matter when interpreting estimates and uncertainty. The registry record does not report distributional checks or diagnostics for the TCSS analysis.

Over-dispersion is a general concern in analyses of count data when the observed variability exceeds what a chosen model assumes. It can make standard errors too small if ignored. The primary outcome in this trial is a score summarized as a mean with standard deviation, not a count outcome in the registry description; no over-dispersion approach is reported. This general concept should not be mistaken for a reported feature of this trial’s analysis.

What do the planning illustrations represent?

The registry’s stated planning assumptions describe an illustration computed from the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantity is participants per arm; time-to-event illustrations use the total number of events. These are planning illustrations, not observed power and not a description of the trial’s original design justification.

In general, sample-size planning asks how much information a future study would need under a set of assumptions about the target effect, variability, significance threshold, and desired power. Such calculations depend on those assumptions and do not show the probability that a completed study’s hypothesis is true. The trial’s own sample-size justification, target power, and original statistical planning details are not reported in the registry record.

What can be said about statistical significance?

A p-value, when reported, measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It does not measure the probability that a treatment is effective or the clinical importance of an estimated difference. A confidence interval complements a p-value by displaying a range of estimates compatible with the data and model. No primary comparison or p-value is reported in the registry record for this analysis, and no significance test should be inferred from the randomized design or completion status.

More broadly, statistical interpretation depends on the analysis population, missing-data handling, outcome definition, model, and any adjustment for multiple analyses. Those details are not fully reported in the registry record. The methods therefore distinguish general statistical principles from procedures actually specified for this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures and 55 analyses. It identifies the TCSS as the primary outcome and lists additional measures, including H-reflex depression, questionnaires, body measurements, and systolic blood pressure. A study with multiple outcomes and analyses can generate many statistical comparisons. In general, the more comparisons considered, the greater the chance that at least one result may appear notable by chance alone if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a complete prespecified statistical analysis plan.

The primary outcome is not reduced in the record to a single comparison across its categories or time points. The registry describes measurement at baseline and after 12 weeks, but the single numerical primary contrast and its uncertainty are not reported in the registry record for this analysis. This limits interpretation because a reader cannot establish which particular contrast is intended to carry the primary inference or assess its precision.

The registry states that the TCSS could not be obtained from one subject in the intervention group and that an intention-to-treat analysis was performed. Intention-to-treat generally refers to analyzing participants according to their randomized groups, regardless of treatment adherence. However, the term does not specify how a missing outcome was handled. The missing-data method, any sensitivity analyses, and whether the intention-to-treat approach applied to every analysis are not reported in the registry record.

The analysis population beyond the stated intention-to-treat analysis is not reported in the registry record. The record also does not describe exclusions, protocol deviations, or outcome-specific denominators for the primary comparison. These omissions matter because missingness and analysis-population choices can affect both estimates and their uncertainty. They do not establish that a bias occurred; they identify information needed to judge how robust the analysis may be.

11. 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 the serious adverse event counts by group. In the intervention group, zero serious adverse events were reported among 20 at risk; zero other adverse events were reported among 20 at risk; and deaths were reported as zero. In the control group, zero serious adverse events were reported among 19 at risk; zero other adverse events were reported among 19 at risk; and deaths were reported as zero.

These are recorded counts, not estimates of the probability of harm. A report of zero events during a trial does not establish that the underlying risk is zero, and it does not rule out events that were not captured or that could occur outside the observed study period. The registry record does not provide additional details about the methods for collecting adverse events, the definition of an event, or the duration of safety follow-up beyond the stated intervention period.

The record lists no top serious-event terms. That is consistent with the reported serious-event counts, but does not provide information about the nature of non-serious symptoms or other safety observations. The figures should be read as the registry’s reported counts for the stated groups, without converting them into percentages or extending them to other populations or treatment durations.

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

The registry describes a completed randomized comparison of cocoa supplementation with a methylcellulose control in a diabetic-neuropathy study. It specifies the regimens, 12-week period, and TCSS as the primary outcome. Those details make the research question and measurement framework understandable, but they do not provide the primary numerical comparison needed to quantify an outcome.

The TCSS is a score from 0 to 19, with higher scores indicating greater severity. The record defines the change as the final measurement minus baseline. These details explain what a reported result would mean in direction, but they do not show whether scores changed, how much they changed, or whether the groups differed. The primary effect estimate and its precision are not reported in the registry record.

Consequently, the trial description should not be interpreted as evidence that cocoa supplementation improved, worsened, or had no effect on neuropathy. The absence of a single primary comparison in the registry entries is not evidence of no difference. It is a limit on what can be concluded from the posted results information available for this analysis.

The zero adverse-event counts are also bounded observations. They describe what the registry reports for the groups, not a guarantee of safety or a prediction for other people, settings, or durations. A completed status confirms that the study is recorded as completed; it does not indicate that any particular result was favorable, statistically significant, or clinically meaningful.

In general, a treatment-effect interpretation requires an estimate, uncertainty, and enough methodological detail to judge the comparison. Clinical importance also requires context about what size of change would matter to patients or researchers. The registry does not report a clinically important TCSS threshold. The current record therefore supports a description of the trial’s design and outcome definitions, but not a conclusion about the clinical effect of the intervention.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its question links a randomized dietary-supplement comparison to a clinical score for peripheral neuropathy. The TCSS combines symptoms, reflexes, and sensory testing, so readers need to understand both the score’s construction and the meaning of a change over time. The registry’s definition of higher scores and its final-minus-baseline convention provide essential direction for interpreting any numerical findings.

The record also illustrates why a completed randomized design is only one part of statistical interpretation. Randomization can support a fair group comparison in general, but readers also need the actual outcome contrast, its uncertainty, and details about the analysis. Here, a single primary comparison and numerical results are not reported in the record details available for this analysis. That leaves the clinical question identifiable while limiting assessment of the evidence about it.

The listed 18 outcome measures and 55 analyses highlight the importance of prespecification and multiplicity. When multiple outcomes and comparisons are considered, the distinction between a primary analysis and additional exploratory findings matters. The registry record does not report the strategy used to address multiplicity, so results across outcomes would require care even if individual findings were available.

The statement that one intervention-group TCSS measurement could not be obtained, alongside the report of an intention-to-treat analysis, also underscores that analysis labels do not substitute for missing-data details. The method used to address missingness can influence estimates and uncertainty; it is not reported in the registry record.

Finally, the safety counts show why event counts should be read with their group context and limitations. Zero reported events are observations during a trial, not proof of no risk. Together, these features make the record a useful case in separating study design, outcome definition, planning assumptions, and observed evidence.

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 interpreting the primary outcome is that the registry record does not provide a single numerical TCSS comparison with an uncertainty measure in the information available for this analysis. Although the outcome is defined at baseline and after 12 weeks, the direction and magnitude of the group contrast cannot be assessed from the reported details.

The record reports that a TCSS measurement could not be obtained from one subject in the intervention group and that an intention-to-treat analysis was performed. It does not describe the missing-data method or whether sensitivity analyses were conducted. The degree to which the missing measurement could affect the primary estimate cannot be assessed without those details and the outcome results.

There are multiple outcome measures and analyses, but the registry does not report the statistical plan for controlling or interpreting multiplicity. It also does not report the model used for the primary analysis, any baseline adjustment, diagnostic checks, or a threshold for clinically important change on the TCSS. These omissions limit assessment of the statistical and clinical meaning of a result.

Details of eligibility criteria, adherence assessment, randomization procedures, masking roles, and safety-event collection are not reported in the registry record. Without those details, readers cannot fully assess applicability, implementation, or the risk of bias. The record’s status as completed and its stated enrollment do not resolve these methodological questions.

These limitations describe what is unavailable in the registry record; they do not show that the trial was improperly conducted. They define the boundaries of interpretation from the information reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Cocoa Supplementation Peripheral and Autonomic Diabetic Neuropathy — NCT05247034.
• Registry record last updated 2025-05-01; status last verified 2025-04.
• Results first posted 2025-05-01.
• 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 record describes a completed randomized, triple-masked, parallel-group study sponsored by Anahuac University, with enrollment of 39. The listed study dates are 2021-06-04 for the start and 2024-06-30 for primary completion. The study compared a 12-week cocoa-capsule regimen with a methylcellulose-capsule control, each alongside a diet for patients with diabetes.

The primary outcome was the TCSS, measured at baseline and after 12 weeks. Higher scores indicate greater severity, and change is defined as final measurement minus baseline. The registry reports that one intervention-group TCSS measurement could not be obtained and states that an intention-to-treat analysis was performed. A single numerical primary comparison, missing-data method, and multiplicity strategy are not reported in the registry record.

Safety entries report zero serious adverse events, zero other adverse events, and zero deaths in both groups. These counts describe the registry entries and do not establish that risk is absent.