Effect of Endoplasmic Reticulum Stress on Metabolic Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Endoplasmic Reticulum Stress on Metabolic Function (NCT00771901), a randomized na study. The primary outcome is Body Composition.

2. Clinical Question

The trial was designed around a metabolic question: whether the two investigational drugs, considered separately against placebo, could affect measures connected to insulin resistance and lipid metabolism in the described population. Its stated rationale links weight gain with reduced insulin action and proposes that reducing endoplasmic reticulum stress may improve insulin action and hepatic lipid metabolism. That rationale is a hypothesis, not a finding.

The primary outcome listed in the registry is fat mass as a percentage, with measurements specified at baseline and four weeks. The secondary outcomes are insulin sensitivity in the liver and VLDL-triglyceride concentration. Those measures connect more directly to the metabolic processes emphasized in the study description, while body composition provides a separate measure of fat mass. The registry record does not give numerical results for these outcomes, so it does not establish whether any changed or differed between groups.

3. Trial Design

The registry describes a randomized, single-masked, parallel study and marks its status as completed. Washington University School of Medicine is listed as the sponsor. The recorded enrollment is 101. The study start is listed as 2008-02, and primary completion as 2014-12. The phase is listed as NA.

The interventions named are tauroursodeoxycholic acid, sodium phenylbutyrate, and placebo. The arm descriptions identify placebo, tauroursodeoxycholic acid, and PBA groups; both active-drug descriptions specify four weeks of treatment. The placebo description says participants received placebo rather than tauroursodeoxycholic acid. The registry does not explain further how the placebo comparator related to each active intervention or provide the allocation ratio.

Randomization means that assignment to study groups is intended to use a chance-based process. In general, this can reduce systematic differences between groups at the outset, although it does not guarantee that every measured or unmeasured characteristic will be balanced. A parallel design means that participants are assigned to a study group and followed in that group rather than each participant receiving all study treatments in sequence. These are general explanations of design terms; the registry record does not report operational details of the randomization process.

Single masking indicates that masking was recorded, but the registry does not identify which parties were masked or describe how masking was maintained. Detailed recruitment, eligibility, treatment administration, adherence, and follow-up information is not reported in the registry record summarized by these study details. Completion status describes the study's recorded status; it does not by itself establish that every planned analysis or outcome result is available.

The posted record identifies 3 outcome measures, including body composition as the primary outcome and liver insulin sensitivity and VLDL-triglyceride concentration as secondary outcomes. It lists 0 analyses. The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. Consequently, the design information identifies the intended framework but does not provide an interpretable treatment-effect estimate.

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.

Before assignment: Screening tests to determine eligibility included: medical hx \& PE, blood tests, resting ECG, OGTT, MRI/MRS/MRE of abdomen/liver, and DEXA scan. Two baseline metabolism studies prior to study drug intervention. There were 67 screen fails, 4 subjects withdrew consent before beginning study intervention.

Overall Study

Reasons for not completing this period:

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 Body Composition, measured over Baseline and four weeks.

The primary outcome is body composition, specifically fat mass (%), reported as a mean with standard deviation. Its timeframe is baseline and four weeks. A percentage expresses the measure relative to a whole, and the registry labels the quantity as fat mass percentage. The record does not further specify the measurement instrument or the exact calculation used to derive this percentage.

Body composition is used in this study as a quantitative measure of fat mass. It addresses a different aspect of the metabolic question from the listed secondary outcomes of insulin sensitivity in the liver and VLDL-triglyceride concentration. Measuring at baseline and again at four weeks can describe values at both time points; by itself, the timeframe does not state how the primary comparison was defined, whether the analysis used change from baseline, or how any comparison between groups was conducted.

A mean describes the central value of a continuous measure, while the standard deviation describes how spread out individual observations are around that mean. These are general statistical interpretations of the registered summary format. The registry record does not report the endpoint means, standard deviations, changes, confidence intervals, or a test result. Therefore, the endpoint definition identifies what was intended to be measured but does not show the observed result or its precision.

The record also does not explain why fat mass percentage was selected as the primary endpoint, how it was measured, or whether it was assessed by a particular instrument or procedure. Such details would help readers judge the measurement's reliability and interpretability, but they are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It records the outcome as fat mass percentage at baseline and four weeks. It does not report a statistical analysis plan or numerical estimates for the endpoint. The explanations below describe general statistical ideas and do not imply that a particular method was used in this study.

What does a mean and standard deviation describe?

For a continuous measure, the mean is the arithmetic average of the observed values. The standard deviation describes the dispersion of observations around that mean. A larger standard deviation indicates that individual observations are more spread out; it is not the same as the uncertainty in the estimated mean. That uncertainty depends on factors such as the amount of available data and variability. The registry reports the intended summary format, but not the actual summaries for the primary endpoint.

Means can be useful for describing a quantitative outcome, but they do not show the entire distribution. For example, a mean and standard deviation do not reveal whether the values are symmetric, whether there are influential outliers, or whether groups have different distribution shapes. These general considerations matter when choosing an analysis and assessing how well its assumptions fit the data. The registry record does not report distribution checks or describe any such diagnostics.

How could baseline and follow-up measurements be compared?

With measurements specified at baseline and four weeks, a study could describe values at each time point, compare follow-up values between groups, compare changes from baseline, or use a model that accounts for repeated measurements. These approaches answer related but not identical questions and can rely on different assumptions. The endpoint timeframe alone does not identify which approach was planned or used. The registry record does not report the precise estimand, contrast, or model for the primary outcome.

In general, a baseline-adjusted comparison can account for chance baseline imbalance and often aims to estimate a treatment-group contrast at follow-up. An analysis of change instead compares the difference between follow-up and baseline within each group. Repeated-measure models can use the pattern across time points and account for correlation between measurements from the same participant. These are general examples, not descriptions of the analysis for this study.

What would an uncertainty interval add?

A point estimate gives a single summary of an effect or contrast. A confidence interval adds information about statistical uncertainty by giving a range of estimates compatible with the data and assumptions under a specified procedure. It is important to distinguish the interval for a group mean from an interval for a between-group contrast: the latter directly addresses a comparative question. The registry record does not report either kind of interval for the primary outcome.

A p-value, when reported, describes how incompatible the observed data are with a specified null model, subject to the model and analysis assumptions. It does not give the probability that the null hypothesis is true, and it does not quantify the size or practical importance of an effect. Neither a p-value nor a confidence interval can be interpreted for this primary outcome because numerical analysis results are not reported in the registry record.

Why do the analysis population and missing data matter?

Interpretation depends on which participants contributed to an analysis and how missing measurements were handled. A complete-case analysis, an analysis using a missing-data model, and an analysis based on all randomized participants can differ in their assumptions and results. If follow-up data are missing, the reason for missingness and the method used to address it may affect how representative the analyzed observations are. The registry record does not report primary-outcome analysis counts, missing-data amounts, or missing-data methods.

Randomization concerns assignment, not necessarily the final set of observations included in each analysis. A reader therefore needs the analyzed population and participant flow to understand whether the randomized groups were preserved in the reported estimate. Such details are not reported in the registry record. The overall enrollment and the at-risk counts listed for adverse events should not be substituted for primary-outcome analysis denominators.

How should the planning illustrations be read?

The record describes sample-size calculations as planning illustrations based on the observed effect, not as the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe a hypothetical planning calculation. The resulting sample size is not observed power, and it does not establish that the study was adequately powered for its actual analyses.

Planning calculations are sensitive to the assumed effect, outcome variability, significance level, allocation, and analysis method. A calculation based on an observed effect can also be unstable when that estimate is imprecise. The registry record does not report a prospective sample-size justification or explain whether the planning illustration matches the original design. The illustrations should therefore be read as conditional scenarios, not as evidence about the reliability of an observed treatment effect.

For continuous outcomes, methods may also need to account for unequal variability, non-normal distributions, or repeated measurements, depending on the data and chosen model. Over-dispersion is a general concern for count outcomes when the observed variability exceeds a model's expectation; it is not a reported property of this continuous primary endpoint. The registry record does not specify a model, diagnostics, or adjustments for the primary outcome. No statistical method beyond the registered summary format can be attributed to the trial from the available record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures: body composition as the primary outcome, with insulin sensitivity in the liver and VLDL-triglyceride concentration as secondary outcomes. Examining multiple outcomes or multiple contrasts can increase the chance of at least one apparently notable result arising by chance. In general, a statistical plan may specify a primary contrast, a testing sequence, or an adjustment for multiplicity. The registry record does not report such a plan, and it does not state whether multiplicity adjustments were made.

The record indicates that the primary outcome has several categories or time points and is not reduced to one comparison. That makes the intended inferential question unclear: the registry does not identify a single contrast for which an estimate or test can be interpreted. It also lists 0 analyses, and no primary or secondary numerical results are reported in the registry record. It is therefore not possible to assess how outcomes or contrasts were selected or prioritized in the analysis.

Missing-data information is also not reported. The record does not give primary-outcome analysis denominators, the number of missing observations, reasons for missingness, or the method used to handle missing data. In general, missingness can affect both the precision and validity of an estimate, particularly if the chance of a missing measurement is related to the outcome or treatment group. Whether that concern arose in this study cannot be determined from the registry record.

The record also does not identify the analysis population, such as whether analyses were intended to include all randomized participants or a subset defined by availability or adherence. Without those details, the analysis population and its relationship to randomization cannot be assessed. No specific missing-data or multiplicity procedure should be inferred.

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 lists serious adverse events, other adverse events, and deaths by safety group. For placebo, 10 were at risk for serious adverse events and 0 were affected; 10 were at risk for other adverse events and 0 were affected; deaths were 0. For tauroursodeoxycholic acid, 10 were at risk for serious adverse events and 0 were affected; 10 were at risk for other adverse events and 0 were affected; deaths were 0. For sodium phenylbutyrate, 6 were at risk for serious adverse events and 0 were affected; 6 were at risk for other adverse events and 0 were affected; deaths were 0.

These figures describe what the registry lists in the safety fields. They do not establish that no adverse experiences of any kind occurred, because the categories are specifically serious adverse events and other adverse events as recorded, and the registry record does not give further event descriptions. Zero affected in the listed categories is not proof of zero risk. The at-risk counts are the relevant denominators for these entries, not the overall enrollment figure.

The registry does not explain why the listed safety denominators differ from enrollment or provide further information on safety surveillance, event collection, or the time period covered by these counts. The figures should therefore be interpreted narrowly as the posted registry counts, not as a comprehensive safety assessment or a comparison of risks.

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

The record establishes that a randomized, single-masked, parallel study was registered as completed and that its primary outcome was body-composition fat mass percentage measured at baseline and four weeks. It identifies tauroursodeoxycholic acid, sodium phenylbutyrate, and placebo as interventions and lists liver insulin sensitivity and VLDL-triglyceride concentration as secondary outcomes. It also records the study's hypothesis about endoplasmic reticulum stress, insulin action, and hepatic lipid metabolism.

Those details describe the study question and intended measurements, not the results. Numerical primary-outcome findings are not reported in the registry record. The record also does not provide numerical secondary-outcome results, treatment-effect estimates, confidence intervals, p-values, or a detailed statistical analysis. It therefore cannot show whether the groups differed, how large any difference was, or how precisely an effect was estimated.

The completed status does not resolve the absence of results. Likewise, a registered biological hypothesis is not evidence that the hypothesized mechanism changed. The listed adverse-event counts are limited to the posted categories and denominators; they cannot establish overall safety or rule out harms. The record does not support conclusions about efficacy, lack of efficacy, or clinical importance.

In general, judging a clinical trial's findings requires more than knowing its design and endpoint labels. Readers need the analyzed group results, a clearly defined comparison, uncertainty estimates, information about analysis populations and missing data, and the methods used to address multiple outcomes or contrasts. These details are not reported in the registry record. The appropriate interpretation is consequently bounded: the record documents the study framework and selected outcomes, while leaving the comparative results unresolved.

The population described in the study summary is people who are obese with insulin resistance and high lipids. Without eligibility details and an analysis population, the extent to which any hypothetical findings would apply beyond the enrolled participants could not be determined. Since results are not reported, no extension to other populations or settings is justified by this record.

13. Why This Trial Matters Statistically

This trial is statistically notable as a record in which the registered design and outcome definitions are more informative than the available outcome results. The record gives a randomized, single-masked, parallel design, names the interventions, and specifies a continuous primary measure at baseline and four weeks. These details identify the broad structure of the intended comparison, but they do not provide the estimates needed to quantify it.

That distinction matters because a study question and a statistical result are not interchangeable. The hypothesis about endoplasmic reticulum stress and metabolic function gives a scientific rationale. The endpoint identifies fat mass percentage as the primary measure. Only a reported analysis can indicate how that measure behaved in the study groups, with what uncertainty, and under what assumptions. The registry record does not supply those results.

The record also illustrates why outcome timing and analysis choices need to be explicit. A baseline and follow-up measurement can support different possible contrasts, and the registry notes that the primary outcome has several categories or time points without reducing it to one comparison. Without a specified contrast and an analysis population, even a reported mean would not necessarily answer a clear treatment-effect question.

Finally, the safety counts and planning illustrations answer different questions from efficacy estimates. The safety entries describe recorded adverse-event counts within their listed denominators; they are not a comprehensive safety analysis. Planning calculations describe hypothetical sample-size scenarios under stated assumptions; they are not observed power and do not substitute for uncertainty around a treatment estimate. Keeping these types of information separate helps prevent design details from being mistaken for findings.

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 central limitation for statistical interpretation is that numerical outcome results are not reported in the registry record. The primary endpoint is defined, but there are no endpoint means, standard deviations, changes, contrasts, confidence intervals, or p-values. Secondary outcomes are named without results. The record therefore does not permit evaluation of effect magnitude, direction, or precision.

The analysis target is not fully specified. Although the primary outcome includes baseline and four-week measurements, the registry does not identify the intended comparison or model. It also does not report analysis-population definitions, endpoint-specific denominators, participant flow, missing-data amounts, or missing-data methods. These omissions limit assessment of both the estimand and the robustness of any possible estimate.

The record does not report a statistical analysis plan, including the handling of multiple outcomes or contrasts, model assumptions, or any adjustment strategy. It gives no endpoint measurement procedure or further detail about how fat mass percentage was derived. The masking entry does not identify which parties were masked. These details would help readers assess risk of bias and measurement validity, but are not reported in the registry record.

The enrollment figure is 101, while the safety groups list at-risk counts of 10, 10, and 6. The registry record does not explain the relationship between those figures. The safety denominators should not be interpreted as primary-outcome sample sizes, and the overall enrollment should not be assumed to represent the number analyzed for the endpoint.

Finally, the record does not report detailed eligibility criteria or the characteristics of participants included in endpoint analyses. This limits assessment of generalizability. The completed status and planning illustrations do not fill these gaps: the former does not establish that results are available, and the latter are not observed power or a substitute for a reported analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Endoplasmic Reticulum Stress on Metabolic Function — NCT00771901.
• Registry record last updated 2018-05-29; status last verified 2018-04.
• Results first posted 2018-05-29.
• 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

NCT00771901, Effect of Endoplasmic Reticulum Stress on Metabolic Function, is listed as a completed randomized, single-masked, parallel study sponsored by Washington University School of Medicine. The registry lists enrollment as 101, phase as NA, start as 2008-02, and primary completion as 2014-12.

The study examined tauroursodeoxycholic acid and sodium phenylbutyrate, with placebo as a comparator. Its primary outcome was body composition, measured as fat mass percentage at baseline and four weeks. Secondary outcomes were insulin sensitivity in the liver and VLDL-triglyceride concentration.

The registry record does not report numerical results for the primary or secondary outcomes, or a detailed statistical analysis. Safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths in each named group, with at-risk counts recorded separately for each category. Those counts do not constitute a complete safety assessment.