(-)- Epicatechin Becker Muscular Dystrophy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for (-)- Epicatechin Becker Muscular Dystrophy (NCT03236662), a na phase 2 study. The primary outcome is Plasma Follistatin.

2. Clinical Question

In statistical terms, the question was whether biomarker or functional measurements in participants receiving epicatechin could yield response magnitudes useful for planning a later study. A single-group extension can describe measurements over time, but it cannot separate changes during the study from changes that might have occurred without the intervention. With the primary outcome not analysed and no concurrent control group, the registry record does not establish a comparative effect. It also does not report a quantitative estimate of change in plasma follistatin.

3. Trial Design

This was a phase 2, single-center, open-label extension study of purified epicatechin in Becker muscular dystrophy. It was designed for participants who had taken part in the earlier UCD0113 proof-of-concept study. The registry lists the study as completed, with a start date of 2016-11 and primary completion in 2017-11. It reports enrollment of 2 participants.

The intervention group was described as receiving (-)-epicatechin 50mg twice per day, or 100mg per day in total. The brief summary describes an 8-week dosing period within a 48-week extension. Planned assessments were described at screening, baseline, and weeks 4, 8, 12, 24, 16 and 48. The sequence of time points is reproduced as recorded; the registry does not explain their ordering or provide details about the assessment schedule for each outcome.

The study had no random allocation, masking, or concurrent control group. The registry therefore describes observations in one treatment group, rather than a randomized comparison. The planned enrollment was up to 10 adults, but lack of funding limited enrollment to 2 participants. The record does not report a protocol rationale for the intended enrollment or a statistical sample-size justification.

Planned outcomes included plasma follistatin as the primary outcome, as well as a graded exercise test using a recumbent cycle ergometer and a 6-minute walk test among the secondary outcomes. The registry lists 12 outcome measures, but reports 0 analyses. For plasma follistatin, it specifically states that the number of evaluable patients was insufficient for analysis. The design and limited enrollment mean the record is descriptive rather than a basis for a controlled estimate of treatment effect.

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: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.

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 Plasma Follistatin, measured over 48 weeks.

The primary endpoint was plasma follistatin, described in the registry as a blood biomarker concentration, with a timeframe of 48 weeks. Follistatin is a biological measurement: it records a concentration in blood rather than a direct measure of walking ability or exercise capacity. The registry does not specify a unit, a summary parameter, or a dispersion measure for this endpoint. It also does not report a numerical result.

Biomarkers can be included in clinical research to assess biological response or to explore whether a measurement may be useful in later studies. Functional outcomes can address different aspects of performance; the registry separately lists a graded exercise test using a recumbent cycle ergometer and a 6-minute walk test as secondary outcomes. These measures should not be treated as interchangeable with the primary biomarker.

The registry gives the primary endpoint a 48-week timeframe but does not report a specific analysis comparing baseline with that assessment. It states that only 2 participants could be enrolled because of lack of funding and that the evaluable population was insufficient to analyse plasma follistatin. Consequently, there is no posted endpoint estimate to interpret, and no estimate of its precision can be described. The record also does not report the criteria used to define a response or a clinically meaningful change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help connect the study design to the conclusions that can reasonably be drawn. In this study, the key features are a single treatment group, no masking, limited enrollment, and the absence of an analysis for the primary outcome. General statistical concepts can clarify why those features matter, but they cannot supply a missing result.

What can a single-group study estimate?

A single-group study can describe measurements collected among people who receive an intervention. If measurements are available at baseline and follow-up, an analysis might describe within-participant changes or the distribution of measurements at a specified time. Such descriptions are not equivalent to a randomized comparison. Without a concurrent control group, a change cannot be attributed specifically to the intervention because time trends, measurement conditions, background variation, and other influences remain possible explanations.

The registry lists allocation as not applicable, masking as none, and the study model as single group. It does not report a comparative analysis or a control arm. Consequently, any interpretation should distinguish a measurement observed during follow-up from a treatment effect. The former is descriptive; the latter requires a defensible comparison that addresses what would have happened without the intervention.

Why do confidence intervals matter?

A confidence interval is a statistical way to express uncertainty around an estimate. It gives a range of values compatible with the data under the analysis assumptions. A narrow interval generally indicates greater precision than a wide interval, though the interval still depends on the study design and methods. An interval is not a guarantee that the true value lies within its endpoints, nor does it address bias from an unsuitable design or analysis.

No confidence interval is reported for plasma follistatin because the registry says the evaluable patients were insufficient for analysis. Without an estimate and its uncertainty, readers cannot judge the magnitude or precision of a primary-outcome response from this record. A statement that an outcome was not analysed should not be read as a null finding or as proof that no change occurred.

Why does enrollment affect precision?

When few participants contribute data, individual observations can have substantial influence on a group summary. The data also provide limited information about variability across participants. This makes estimates unstable and intervals, if calculated, potentially imprecise. The record reports enrollment of 2 and says this was below the intended maximum because of lack of funding. The registry does not provide a sample-size justification or a formal assessment of the precision that the planned enrollment would have achieved.

Small enrollment is not a statistical flaw in every exploratory study; it does, however, constrain the purpose and interpretation of the results. In this record, the primary outcome was not analysed, so there is no reported estimate from which to assess its precision. No claim about the power of the completed study should be inferred from planning illustrations.

How should planning illustrations be understood?

A sample-size calculation uses assumptions about a future design and the effect a study is intended to detect. The registry’s stated assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect described as a stated fraction of an observed effect. These are planning assumptions, not a description of the actual single-group design. They do not demonstrate that the extension had a particular probability of finding a result.

Sample-size calculations are conditional on the assumptions used. If the effect estimate used for planning is unstable, the planning result will also be sensitive to that uncertainty. A calculation based on an observed effect is not a substitute for a prospectively justified design, and it must not be described as observed power. The registry does not report the original trial’s statistical sample-size plan, interim analyses, or detailed statistical analysis plan.

Over-dispersion is a general concept relevant to count outcomes: it occurs when observed variability exceeds what a model assumes. If ignored, standard errors and resulting uncertainty estimates can be misleading. The registry information does not identify a count-data analysis or report a model for the listed primary biomarker. Over-dispersion therefore should not be presumed to have been assessed in this study.

What does a significance threshold mean?

In general, a significance threshold is a rule used to judge how unusual data would be under a specified null hypothesis and analysis model. It does not measure the probability that a treatment works, and it does not communicate the size or practical importance of an effect. A p-value, if reported, should be interpreted alongside the estimate, its uncertainty, and the design. The registry reports 0 analyses and does not post a primary-outcome p-value.

Even when an analysis is possible, statistical evidence from a single-group design cannot by itself resolve the lack of a concurrent comparator. Statistical methods can quantify uncertainty under assumptions; they cannot remove design limitations or create unobserved control data. Here, the key methodological conclusion is that the primary outcome lacks a reported analysis and the design is not comparative.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and identifies plasma follistatin as the primary outcome. It also lists a graded exercise test using a recumbent cycle ergometer and a 6-minute walk test among the secondary outcomes. Considering multiple outcomes can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently unusual result can increase if each is assessed separately. Researchers may address this through prespecified outcome hierarchies or statistical adjustments, but the registry record does not report a multiplicity strategy. That absence should not be interpreted as evidence that no strategy existed outside the record.

The record lists 0 analyses and states that the number of evaluable patients was insufficient to analyse the primary plasma follistatin outcome. It does not report a numerical primary result or outcome-level estimates for the listed secondary measures in the information recorded. Therefore, there is no basis in the registry record for describing which outcomes were statistically tested, whether any multiplicity adjustment was applied, or how results across outcomes were interpreted.

Missing-data details are also not reported in the registry record. The primary-outcome description establishes that the evaluable population was insufficient for analysis, but it does not specify how many measurements were unavailable, why they were unavailable, or whether missingness occurred at a particular visit. The analysis populations, participant-level exclusions, and methods for handling missing data are not reported in the registry record.

The record does not report a statistical analysis plan, interim analyses, or methods defining the analysis population. These omissions limit assessment of whether analyses followed prespecified procedures. They do not establish that such procedures were absent; they mean that readers cannot evaluate them from the registry record.

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 adverse-event counts for the Treatment group. The serious adverse-event figures are 0 affected among 2 at risk. The other adverse-event figures are also 0 affected among 2 at risk, and deaths are recorded as 0. No serious adverse-event terms are listed.

These are counts recorded for the enrolled group, not estimates of comparative risk. Because the study had no concurrent control group, the counts do not show how event occurrence compared with an untreated or alternative-treatment group. With enrollment of 2, the absence of a recorded event in the group should not be interpreted as evidence that an event cannot occur or that the intervention has a particular safety profile.

The registry record does not provide additional detail about adverse-event definitions, ascertainment procedures, event timing, or the duration of safety follow-up. It also does not list individual event descriptions. The reported zeros should therefore be read narrowly as the counts entered in the registry, rather than as a comprehensive conclusion about safety.

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

The registry record documents a completed, open-label extension study of purified (-)-epicatechin in Becker muscular dystrophy. It records enrollment of 2 participants and a planned maximum enrollment of up to 10 adults. It identifies plasma follistatin at 48 weeks as the primary outcome, while also listing exercise-related secondary outcomes. These registry entries describe the study’s scope and intended measurements.

The primary plasma follistatin outcome was not analysed because the number of evaluable patients was insufficient. As a result, the registry offers no estimate of the biomarker concentration or change, and no measure of precision for that outcome. The record does not establish that the biomarker increased, decreased, or remained stable. No inference about the direction or size of a primary-outcome effect is justified from an analysis that was not performed.

The design also does not support a controlled estimate of treatment effect. A single group receiving an intervention cannot show what would have happened to the same participants under a comparator condition. Open-label conduct means masking was absent, and the registry reports no concurrent control group. Any observed measurements, if available elsewhere, would need to be interpreted as observations within this design, not as proof that the intervention caused a change.

The record’s stated exploratory goal was to identify biological or functional outcomes that might inform planning for a later phase II B study with a sample size of 30 individuals. That aim is not equivalent to demonstrating efficacy, confirming a biomarker, or validating a functional measure. The registry does not report a primary-outcome analysis that could establish whether the intended signal was observed.

The adverse-event record lists no serious adverse events, other adverse events, or deaths among the reported group counts. These counts are limited observations in a very small, uncontrolled study and do not establish comparative safety. Taken together, the record is useful for understanding the study design and why its primary endpoint could not be evaluated, but it cannot establish treatment benefit, lack of benefit, or a precise safety profile.

13. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the difference between an intended study and the data that can ultimately support analysis. The registry describes a 48-week extension with several biological and functional outcome measures, but reports that lack of funding limited enrollment to 2 participants. It further states that the number of evaluable patients was insufficient to analyse the primary plasma follistatin outcome. A clearly specified endpoint cannot yield an interpretable estimate when the available evaluable data do not support the planned analysis.

The design also shows why study structure matters alongside sample size. Even if measurements are collected over time in a treatment group, the absence of a concurrent comparator prevents a direct estimate of what would have occurred without the intervention. Statistical summaries can describe available observations, but they do not independently resolve confounding, time effects, or other explanations for change.

The registry’s broader objective was exploratory: identify response magnitudes in biological or performance measures that could support planning for later research. Such work can be useful when it produces analysable, clearly described estimates. In this record, however, the primary measure was not analysed, and the registry lists 0 analyses. The goal does not substitute for reported results or establish that any measure was suitable for a subsequent study.

Finally, the record helps readers distinguish planning calculations from evidence. Illustrative calculations based on assumed effects and a hypothetical two-arm allocation do not describe the completed single-group extension and are not observed power. The main statistical lesson is that design, evaluable data, and transparent outcome analyses jointly determine what can be concluded. Here, those limits sharply restrict interpretation.

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.

Several limitations specific to this study constrain interpretation. First, enrollment was 2, below the intended maximum of up to 10 adults. The registry attributes the limited enrollment to lack of funding. The primary outcome description states that the number of evaluable patients was insufficient for analysis. The record therefore provides neither a plasma follistatin estimate nor its uncertainty.

Second, the study was open-label and single-group, with no concurrent comparator. This design cannot distinguish an intervention-associated change from other explanations for measurements over time. The registry also does not report masking, allocation procedures beyond allocation being not applicable, or an adjusted comparative analysis.

Third, although the registry lists 12 outcome measures, it reports 0 analyses. The primary outcome is described, and two exercise tests are named as secondary outcomes, but outcome-level results are not available in the registry record. Details about the analysis population, missing measurements, and missing-data methods are not reported in the registry record. Multiplicity methods and a statistical analysis plan are also not reported in the registry record.

Fourth, the registry does not specify a unit, summary parameter, or dispersion measure for plasma follistatin. It gives a 48-week timeframe but does not report the estimate or a measure of precision. The brief summary describes dosing for 8 weeks within the 48-week extension, but the available record does not give sufficient detail to assess adherence or exposure over time.

These limitations mean that the registry record can describe the study’s intended purpose and its inability to analyse the primary outcome, but cannot quantify a treatment effect or provide a robust comparative safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: (-)- Epicatechin Becker Muscular Dystrophy — NCT03236662.
• Registry record last updated 2021-11-24; status last verified 2021-11.
• Results first posted 2021-07-26.
• 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.

18. Record Summary

The registry identifies NCT03236662 as a completed phase 2, single-center, open-label extension study of purified (-)-epicatechin in Becker muscular dystrophy. The study was intended for adults who had participated in the earlier UCD0113 study. The intervention was described as 50mg twice per day, for a total daily dose of 100mg, with 8 weeks of dosing in a 48-week extension.

Enrollment was 2, and the registry states that lack of funding prevented enrollment of the planned maximum of up to 10 adults. Plasma follistatin at 48 weeks was the primary outcome. The registry says the number of evaluable patients was insufficient to analyse it. It lists a graded exercise test using a recumbent cycle ergometer and a 6-minute walk test among secondary outcomes, and reports 0 analyses.

The study had no concurrent control group or masking. The adverse-event record lists 0 serious adverse events, 0 other adverse events, and 0 deaths. The record does not provide a numerical primary-outcome result or a controlled estimate of treatment effect.