Beta Glucosylceramide for Treatment of NASH: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beta Glucosylceramide for Treatment of NASH (NCT02126306), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With a Decrease of 2 Points in the Non-Alcoholic Fatty Liver Disease Activity Score (NAS) Analysis is Per Protocol.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-masked, parallel-group trial of beta glucosylceramide for treatment of non-alcoholic steatohepatitis. Its listed phases are Phase 1 and Phase 2. The recorded enrollment is 23. The two interventions were beta glucosylceramide and placebo, each described as administered orally daily; the placebo is further described as normal saline. The record does not report additional details about sequence generation, concealment of allocation, or the masking procedures.

The listed study status is completed. The recorded start is 2006-01, and primary completion is recorded as 2010-12. These dates describe the registry record and do not establish when any particular participant entered or completed treatment. The record does not report further information about the trial schedule, treatment duration beyond the outcome timeframe, or follow-up after the primary assessment.

The primary outcome compares the total NAS score at baseline with the score at week 40. The measure is based on liver biopsy before and after treatment. A decrease of at least 2 points is classified as improvement for this endpoint, and the primary result is described as per protocol. The record reports 10 participants in the placebo arm and 13 in the beta glucosylceramide arm for the outcome. It does not explain how the per-protocol analysis population was defined or whether any enrolled participants were excluded from that analysis.

The sponsor is Hadassah Medical Organization. The registry record does not report a sample-size justification, planned interim analyses, or further statistical design details. The planning assumptions accompanying the posted sample-size illustrations describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, but those are planning assumptions based on the observed effect, not a description of the trial's original design or its observed statistical power.

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 Number of Participants With a Decrease of 2 Points in the Non-Alcoholic Fatty Liver Disease Activity Score (NAS) Analysis is Per Protocol, measured over Total score from baseline compared with week 40..

The primary endpoint counts participants whose total Non-Alcoholic Fatty Liver Disease Activity Score (NAS) decreased by at least 2 points from baseline to week 40. The outcome is based on liver biopsy performed before and after treatment. The registry record describes the analysis as per protocol and states that no subscales were used for the data analysis. It also describes a decrease of at least 2 points as improvement and an increase of at least 2 points as deterioration.

Turning a score change into a responder count creates a binary outcome: each participant is classified according to whether the specified decrease was reached. Such thresholds can make a result easier to interpret as a count of participants meeting a defined criterion, while the full score change and changes that do not reach the threshold are not represented by that count. The registry record does not report the distribution of individual score changes, baseline scores, or the number of participants whose score increased or changed by less than the threshold.

The endpoint is specific to the stated biopsy-based score and timeframe. It does not summarize every possible change in disease status, and the responder definition should not be confused with a comparison of mean score changes. The registry record reports 10 responders in the placebo arm and 13 in the beta glucosylceramide arm, with the same numbers recorded as the respective arm counts for this outcome. It does not report a separate secondary outcome in the posted results.

7. Results Posted in the Registry

• Beta Glucosylceramide: 100.0% (13/13) versus 100.0% (10/10) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary responder endpoint represent?

A binary endpoint divides outcome observations into categories, such as meeting or not meeting a prespecified criterion. In this trial, the stated criterion is a decrease of at least 2 points in total NAS from baseline at week 40. The recorded value is a participant count, not a continuous score summary. This means that the endpoint does not preserve how far a participant's score changed once the threshold was reached, nor does it show the individual changes among participants who did not meet the threshold.

Binary outcomes can be summarized by the proportion meeting the criterion in each group and by a contrast between those proportions. The risk difference is an absolute contrast: it expresses how far apart the group proportions are on the probability scale. A value of 0.0 means the posted point estimates are equal. A risk ratio compares the proportions multiplicatively; the record reports 1.0. Both summaries convey the same absence of a difference in the displayed point estimates, but neither alone describes the endpoint's full clinical context or the certainty of a population-level effect.

What does the risk difference say?

The registry record reports a risk difference of 0.0 for beta glucosylceramide relative to placebo. In general, a risk difference is useful because its scale corresponds to an absolute difference in event probability. It is sensitive to the event rates in the groups and is directly interpretable as a gap between those rates. The estimate is not a statement that every possible effect is zero: it is the point estimate derived for the posted comparison. The accompanying interval is intended to communicate uncertainty around an estimate, but the record displays both limits at 0.0.

The arm summaries show 10 responders out of 10 recorded for placebo and 13 out of 13 recorded for beta glucosylceramide. These are the outcome counts and arm counts as entered in the registry record. No additional rate calculation is needed to describe them. The equality of the displayed responder proportions is reflected in the zero risk difference and the reported risk ratio of 1.0.

How should the p-value be read?

The comparison reports p = 1.0. In general, a p-value describes how compatible observed data are with a specified null model, when the assumptions of the test hold. It is not the probability that the null hypothesis is true, and it is not a measure of the size or importance of an effect. A p-value of 1.0 in the posted comparison does not establish equivalence and does not guarantee that the true effect is exactly zero.

The registry record does not identify the test used to obtain the p-value, describe its assumptions, or report an analysis plan. It is therefore not possible to assess from the record whether the test was prespecified or how it handled the sparse binary outcome. The reported value should be treated as the registry's posted comparison statistic, without attributing an unreported method to it.

Why does the per-protocol label matter?

A per-protocol analysis is generally intended to evaluate outcomes among participants meeting specified protocol requirements. The definition can vary by trial and must be documented to know which participants were included and how protocol deviations were handled. The primary endpoint is labeled per protocol, but the registry record does not define the analysis population, describe exclusions, or report an intention-to-treat analysis. The counts listed for the outcome match the arm counts in the record, but that alone does not provide the missing analysis-population rules.

Analysis population affects interpretation because the comparison depends on which observations enter the calculation. If outcomes are unavailable or participants are excluded, the reasons and handling can matter. The registry record does not report whether missing outcome measurements occurred, how any missing values were treated, or whether all randomized participants contributed to the primary analysis. No assumptions about these matters should be inferred from the posted counts.

What do the planning assumptions mean?

The record's sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. In general, a sample-size calculation asks how many observations might be needed under chosen assumptions to detect a specified effect with a chosen power. A planning illustration based on an observed effect is not the trial's original design calculation and is not observed power. The record does not report the trial's own sample-size justification or its planned power.

The planning description also says that the effect to detect is a stated fraction of the observed effect. No resulting planning counts are included in the registry entries for this explanation. A planning exercise of that kind depends on assumptions about the target effect and analysis; its output should be understood as a hypothetical design aid, not as an additional finding from this trial. In a binary endpoint with a very small number of recorded observations, such calculations are especially dependent on the chosen assumptions and method.

More generally, normal approximations are simplifications used in statistical calculations. Their performance depends on the data and setting. For binary outcomes with limited observations, alternative methods may be considered in a full statistical analysis, but the registry record does not state which method generated the comparison or whether alternatives were evaluated. It would be inappropriate to reconstruct or substitute an analysis without those details.

What information is absent?

The record reports one primary outcome measure and zero secondary outcomes posted. It reports zero analyses, while also displaying a primary comparison; it does not explain how the analysis count relates to that comparison. It does not report covariate adjustment, a statistical analysis plan, interim analyses, multiplicity procedures, or sensitivity analyses. These omissions limit assessment of whether the reported comparison reflects the prespecified analysis and how robust it is to alternative analytic choices.

General statistical interpretation also depends on study conduct and measurement quality. Randomization can support a fair comparison when it is implemented appropriately, while masking may reduce some forms of bias. The registry record identifies randomized and double-masked design features but does not report enough procedural detail to assess their implementation. These design labels are informative, but they do not replace information about allocation, masking procedures, outcome ascertainment, analysis populations, and missing observations.

10. Confidence Intervals and Precision

The primary comparison reports a risk difference of 0.0, with a confidence interval from 0.0 to 0.0. A confidence interval is generally intended to show a range of values compatible with the data and the method used, under the method's assumptions. Its width is often read as an indication of statistical precision: a wider interval represents a broader range, while a narrower interval represents a more restricted displayed range. In this record, the reported limits coincide with the point estimate.

That zero-width presentation should be interpreted cautiously. It is what the registry record displays, but it should not be taken to mean that the population effect is known with absolute certainty. The record does not report how the interval was calculated, what method was used for the binary outcome, or whether any rounding or reporting process affected the displayed limits. There is not enough information in the record to resolve why the interval has no displayed width.

The outcome counts are 10 responders in the placebo arm and 13 in the beta glucosylceramide arm, with recorded arm counts of 10 and 13. The limited number of observations makes careful consideration of uncertainty important, but no alternative interval or analysis is reported. It is therefore appropriate to state both the posted interval and the limits of what can be inferred from its presentation, rather than to replace it with a newly calculated interval.

The p-value of 1.0 is not a substitute for a confidence interval and does not measure precision. The risk difference and its interval concern the comparative estimate, while the p-value concerns a test under a null model. Neither statistic establishes clinical equivalence. The record does not report an equivalence margin or another criterion defining how small a difference would be considered unimportant.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and zero secondary outcomes posted. It does not report a multiplicity-adjustment procedure or explain whether any additional outcomes were assessed but not posted. When multiple outcomes or repeated comparisons are tested, multiplicity can affect how statistical evidence is interpreted; methods may be used to control the chance of false-positive findings across a family of tests. That general concern cannot be evaluated fully from the record because the analysis plan and complete set of tested outcomes are not reported.

The primary endpoint is described as a per-protocol analysis. The record does not state how the per-protocol population was defined, whether all randomized participants were included, or how protocol deviations were handled. Although the reported outcome counts match the recorded arm counts, that matching does not establish the rules used to construct the analysis population. No intention-to-treat result is posted.

Missing-data status and handling are also not reported in the registry record. It does not state whether any NAS assessments were unavailable, what reasons might have applied, or whether any imputation or other missing-data method was used. Missing outcomes can affect a binary responder analysis because the classification depends on having the relevant baseline and week 40 measurements. Without details, it is not possible to determine whether missingness occurred or how it could influence the result.

The record does not report a statistical analysis plan, sensitivity analyses, or interim analyses. These absences limit the ability to assess prespecification and robustness. They should be treated as unreported information, rather than evidence that such procedures were or were not used.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious adverse event figures report zero affected participants among 10 at risk in the placebo arm and zero among 13 at risk in the beta glucosylceramide arm. The other adverse event figures also report zero affected participants among the recorded at-risk counts in both arms. No serious adverse event terms are listed.

These entries describe what the registry record reports for the listed safety categories. They do not establish that no adverse events of any kind occurred, because the figures concern the recorded categories and the record does not provide detailed event descriptions beyond the serious-event terms list. A zero count in a trial with limited recorded observations also cannot rule out events that were not observed or reported. The registry record does not describe the adverse-event collection methods or reporting period in further detail.

Deaths are recorded as null for both arms. A null entry is not the same as a reported zero; the number of deaths is therefore not reported in the registry record. The safety entries should be read separately from the primary NAS responder outcome. They do not provide a basis for broader conclusions about safety beyond the figures and categories explicitly recorded.

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

The posted primary result describes a binary NAS responder outcome at week 40, assessed per protocol. The registry record reports 10 responders in the placebo arm and 13 in the beta glucosylceramide arm, with arm counts of 10 and 13. Its comparative estimate is a risk difference of 0.0, with a confidence interval from 0.0 to 0.0 and p = 1.0. In the displayed data, the responder proportion is the same in both arms.

This result does not establish that the interventions are equivalent. Equivalence requires a defined margin and an analysis designed to determine whether the uncertainty around an effect falls within that margin; the registry record reports no such margin or analysis. The displayed zero-width confidence interval should not be treated as proof of no uncertainty, particularly because the record does not explain the interval method.

The endpoint also represents a specific thresholded change in a biopsy-based score, not every possible change in score or disease status. The registry record does not report individual score changes, baseline score distributions, or other clinical outcomes. Its outcome result therefore should not be generalized to measures that are not included in the posted results.

The primary analysis is labeled per protocol, but its population rules are not reported. There is no posted intention-to-treat result, and the record does not describe missing-data handling or protocol deviations. The trial design is recorded as randomized and double-masked, but procedural details are not reported. These gaps constrain how confidently the comparison can be interpreted beyond its literal registry presentation.

The result should also be distinguished from a claim about treatment effect or clinical benefit. It records a comparison of responder counts and statistical summaries; it does not by itself answer questions about other outcomes, longer-term effects, or populations not described in the record. Safety entries report no affected participants in the listed adverse-event categories, while death counts are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates how a binary responder definition can make an outcome easy to state while concealing information about the underlying score changes. The primary endpoint counts whether each participant crossed a stated NAS threshold. The resulting counts do not describe the size or distribution of score changes, the number whose score worsened by a different amount, or changes that fell short of the responder threshold. For interpretation, the endpoint definition and the underlying measurement are both relevant.

It also illustrates why point estimates, confidence intervals, and p-values answer different questions. The posted risk difference is 0.0, the reported interval has both limits at 0.0, and the p-value is 1.0. The point estimate describes the observed contrast, the interval is intended to represent uncertainty under a method, and the p-value concerns a test. Those statistics should not be collapsed into a single claim of no effect. The registry record does not describe the method behind the interval or test.

The per-protocol label highlights the importance of analysis-population definitions. A result is difficult to evaluate fully when the record does not explain who qualified for the analysis, whether observations were missing, or how deviations were handled. Matching outcome and arm counts do not replace those definitions.

Finally, planning illustrations based on an observed effect are distinct from a trial's original design justification and from observed power. The registry record gives assumptions for planning illustrations but does not report the trial's own sample-size justification. Keeping these distinctions clear helps prevent a retrospective planning exercise from being mistaken for a design feature or a result.

15. 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 important details about the primary analysis unreported. Although the endpoint is labeled per protocol, the criteria for that population and the handling of protocol deviations are not described. No intention-to-treat result is posted. Missing outcome status, reasons for any unavailable measurements, and missing-data methods are also not reported in the registry record.

The comparative statistics have limited supporting detail. The record reports a risk difference of 0.0, an interval from 0.0 to 0.0, and p = 1.0, but it does not identify the statistical method used for the interval or test. The zero-width interval should not be read as proof of certainty. The record also does not report an analysis plan, adjustment variables, sensitivity analyses, or interim analyses.

The endpoint is a threshold-based responder count from a biopsy-based score, and the posted result does not include individual score changes or a continuous-score summary. No secondary outcomes are posted. The record therefore offers limited information about outcomes beyond this specific responder definition.

The registry identifies the listed condition as Compliance Behavior, while the trial title and primary outcome concern NASH and NAS. The population field for the primary outcome is blank, and eligibility details are not reported. The adverse-event entries list zero affected participants in the reported categories, but deaths are null and event-collection details are not stated. These are limitations of what the registry record reports, not evidence that unreported information had a particular value.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Beta Glucosylceramide for Treatment of NASH — NCT02126306.
• Registry record last updated 2014-10-30; status last verified 2006-01.
• Results first posted 2014-08-18.
• 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.

19. Record Summary

The registry record describes NCT02126306, titled Beta Glucosylceramide for Treatment of NASH, as a completed randomized, double-masked, parallel trial in Phase 1 and Phase 2. Enrollment is recorded as 23. The interventions were daily oral beta glucosylceramide and daily oral normal-saline placebo. The sponsor is Hadassah Medical Organization. The recorded start is 2006-01 and primary completion is 2010-12.

The primary outcome is the number of participants with a decrease of at least 2 points in total NAS from baseline to week 40, analyzed per protocol. The registry reports 10 responders among 10 recorded in the placebo arm and 13 among 13 recorded in the beta glucosylceramide arm. The risk difference is 0.0, with an interval from 0.0 to 0.0 and p = 1.0. Serious and other adverse-event counts are recorded as zero in both arms; death counts are not reported in the registry record.

The record does not report a secondary outcome, analysis-population definition, missing-data handling, or the methods used for the comparative interval and test.