This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Clinical Studies on Bile Acids in Barrett's Esophagus (NCT00858858), a non-randomized na study. The primary outcome is Protection Against DNA Damage by UDCA.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00858858 |
| Phase | NA |
| Condition | Gastroesophageal Reflux Disease |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | US Department of Veterans Affairs |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Barrett’s esophagus and gastroesophageal reflux disease. The primary endpoint description specifies that only metaplastic epithelium was evaluated; squamous epithelium was not assessed.
Intervention
Oral ursodeoxycholic acid (UDCA), at 10 mg/kg qd for 8 weeks, within a study sequence that also included esophageal perfusions with bile acids.
Comparator
No separate control group is described. The registry characterizes the study as non-randomized and single-group, with measurements around bile-acid perfusion rather than a like-for-like comparison between randomized arms.
Primary question
After 8 weeks of UDCA treatment, how do p-H2AX levels—used as a measure of DNA damage—change following DCA perfusion in the evaluated metaplastic epithelium?
The registry presents two broad aims. One concerns the effects of bile salts on DNA injury and growth-related signaling in esophageal cells from patients with gastroesophageal reflux disease. The other concerns whether UDCA-related changes in bile composition alter DNA injury, signaling, or other types of cellular damage. The primary endpoint focuses on p-H2AX levels after DCA perfusion following oral UDCA treatment.
The endpoint description frames a possible protective pattern as little or no significant change in p-H2AX levels before and after perfusion. That is the study’s stated rationale, not a reported finding. The numerical measurements, estimated change, uncertainty, and statistical test result are not reported in the registry record. The study therefore raises a biological question, but the registry information does not establish what the measured endpoint showed.
3. Trial Design
The registry identifies this as a completed, non-randomized, single-group study with no masking. It lists an enrollment of 60 and names the US Department of Veterans Affairs as sponsor. The registry dates the study start to 2009-03 and primary completion to 2013-03. Its phase is listed as NA. The listed condition is gastroesophageal reflux disease, while the primary endpoint population is described as patients with Barrett’s esophagus.
The arm description says that patients received DCA and UDCA perfusion of the esophagus one year apart, followed by 8 weeks of oral UDCA at 10 mg/kg qd, and then a final DCA perfusion. This is a within-study sequence, not a randomized comparison of treatment groups. The registry does not report a separate untreated or placebo group. Consequently, the design does not supply the usual concurrent control for separating treatment effects from changes over time, procedural effects, or other influences.
The primary endpoint is described as a change in p-H2AX levels after DCA perfusion in patients treated with oral UDCA. The registry specifies that only metaplastic epithelium was evaluated. It says squamous epithelium was not assessed because later in vitro work showed no DNA damage from DCA exposure in squamous cells, making oral UDCA treatment in that tissue seem unwarranted to the investigators.
Enrollment is not the same as the number with usable endpoint measurements. The number contributing to the primary endpoint, the handling of incomplete observations, and the specific analysis population are not reported in the registry record. Although one outcome measure is listed, the record reports zero analyses. Thus the design and endpoint can be described, but no primary endpoint estimate or inferential result can be reconstructed from the registry information.
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
| Stage | Arm 1 |
|---|---|
| STARTED | 60 |
| COMPLETED | 42 |
| NOT COMPLETED | 18 |
Analysis population for the primary outcome, as defined in the registry: Patients with Barrett's esophagus, only metaplastic epithelium evaluated. No data were collected from squamous epithelium as originally planned because our in vitro studies subsequently showed that DCA exposure did not cause DNA damage in squamous cells and, therefore, oral UDCA treatment would be meaningless for squamous esophagus.
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.
| Characteristic | Unit | Arm 1 |
|---|---|---|
| Participants analysed | 42 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 37 |
| Age, Categorical: >=65 years | Participants | 5 |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 38 |
| Region of Enrollment: United States | participants | 42 |
6. Primary Endpoint
The registry lists the primary outcome as Protection Against DNA Damage by UDCA, measured over After 8 weeks of UDCA treatment.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | Relative Densitometry Units |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is p-H2AX level, expressed in relative densitometry units, after 8 weeks of UDCA treatment and DCA perfusion. The registry identifies p-H2AX as a measure of DNA damage. The stated outcome is the change in its level, with measurements framed around perfusion in patients treated with oral UDCA. The record labels the outcome as a mean of a continuous measure and identifies standard error as its dispersion measure.
In general, a biomarker endpoint can provide a measurable signal related to a biological process that may be difficult to observe directly. Here, p-H2AX is used as an indicator of DNA injury in esophageal tissue. The study’s stated rationale is that if UDCA protects against bile acid-induced DNA damage, p-H2AX levels before and after perfusion should not change significantly. This is a hypothesis about the expected pattern, not evidence that such a pattern occurred.
The registry does not report the observed mean levels, the change in relative densitometry units, the number of tissue samples or participants analyzed, or an uncertainty interval. It also does not give a test statistic or p-value. Without those results, the direction, magnitude, and precision of the endpoint change cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes the broad design and the endpoint of interest, but it does not report the numerical primary outcome or an analysis of that outcome. Accordingly, there is no posted estimate of the change in p-H2AX levels, no confidence interval, and no reported significance test. The biological question is clear; the quantitative answer is not available in the registry record.
The stated endpoint is a continuous measurement reported as a mean, with standard error named as the dispersion measure. Those labels describe how results would be summarized, but they do not reveal the actual average level or how variable the observed measurements were. A mean alone would describe the central value, while a measure of uncertainty would help indicate how precisely that value had been estimated. Neither numerical result is reported.
The registry’s wording about no significant change is conditional: it describes what would be expected if UDCA protected against bile-acid-related DNA damage. It should not be read as a report that no significant change was observed. A stated expectation, a study objective, and a statistical result are different kinds of information. The latter is absent from the posted record.
The non-randomized single-group structure also matters for interpretation. In general, measurements in the same group over a sequence of procedures can show whether values changed across the observed conditions. But without a concurrent control group, a change—or the absence of a change—cannot by itself isolate the contribution of UDCA from other time-related, procedural, or measurement influences. The registry does not report an adjusted analysis or other approach to address such influences.
The listed enrollment of 60 does not establish how many participants contributed to the primary endpoint. The registry does not report endpoint-specific sample size, missing measurements, or reasons for non-assessment. Its adverse-event information is reported separately and does not fill this gap in the efficacy endpoint data.
The appropriate statistical reading is therefore limited: the record describes a biological hypothesis and a continuous biomarker endpoint in a single-group study, but does not provide the outcome estimates needed to judge the observed pattern or its precision. No conclusion about the magnitude or statistical significance of the primary endpoint can be drawn from the registry record.
9. Statistical Methods Explained
The registry identifies the primary measure as a mean of a continuous outcome and names standard error as the dispersion measure. A continuous outcome can take values across a measurement scale rather than being limited to event counts or categories. Relative densitometry units are the stated scale for p-H2AX. The record does not provide numerical endpoint values, so the mean and its uncertainty cannot be described quantitatively.
What does a mean describe?
In general, a mean is a measure of the central location of observed values. It can summarize biomarker measurements across the participants or tissue observations included in an analysis. The mean does not describe the full spread or shape of those observations. Different underlying data patterns can have the same mean, so a mean is most informative when accompanied by a measure of variability and clear information about the observations included.
The registry names standard error as the dispersion measure. In general, standard error describes the estimated precision of a sample statistic, such as a mean. It is not the same as the spread of individual observations: standard deviation describes variation among observations, while standard error concerns uncertainty in the estimated mean. A small standard error can indicate a more precise estimate, but interpretation still depends on the data and analysis. The actual standard error is not reported in the registry record.
How should a before-and-after outcome be understood?
When measurements are taken from the same participant under more than one condition or at more than one time, those observations are related. In general, an analysis that accounts for this within-participant relationship can be more appropriate than treating every measurement as independent. The endpoint description refers to p-H2AX levels before and after perfusion, but the specific statistical test, model, and handling of repeated observations are not reported in the registry record. It is therefore not possible to say which method was used or whether it accounted for that relationship.
A change score would describe the difference between measurements for an individual or group, depending on how the analysis is defined. The registry describes a change in p-H2AX levels but does not give a numerical change or specify its precise calculation. No recalculated estimate is available from the posted summary information. The record reports zero analyses, so there is no sponsor analysis to compare with a simple recalculation.
What would a confidence interval add?
In general, a confidence interval expresses uncertainty around an estimated quantity, such as a mean change. Its width reflects the precision of the estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, but the interval must be considered alongside the scale of the outcome and the question being asked. The registry does not report a confidence interval for the primary endpoint.
A significance test addresses compatibility between observed data and a specified null hypothesis, under the assumptions of the test. A p-value is not a measure of effect size, clinical importance, or the probability that the null hypothesis is true. Nor does a non-significant result establish that there was no change. The registry does not report a primary endpoint p-value, test statistic, or test specification. The endpoint description’s reference to levels that “should not change significantly” is a conditional statement of the investigators’ rationale rather than a posted test result.
Why does the design affect the analysis?
The study is listed as non-randomized and single-group, with no masking. General statistical interpretation of a single group depends on what measurements are compared and how they are collected. Repeated measurements can describe within-group patterns, but without a concurrent control group, other explanations for a difference over time may remain. Lack of masking can also matter in general when judgments or measurements could be influenced by knowledge of the treatment sequence. The registry does not report procedures for reducing measurement bias.
The record’s sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the assumptions refer to total events, and for other outcomes they refer to participants per arm. These are planning assumptions, not a report of the trial’s design or its observed power. They also do not match the registry’s description of a single-group, non-randomized study. Numerical planning estimates and the observed effect needed to interpret such an illustration are not reported in the registry record.
In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If present, uncertainty estimates from a model that understates variability can be too small, leading to overly precise inference. This concept is relevant to some outcome models, particularly count data, but the primary endpoint is described as continuous, and the registry does not report a model or indicate that over-dispersion was assessed.
Overall, the registry gives enough information to identify the endpoint type and some design features, but not enough to reproduce or evaluate the statistical analysis. The analysis method, assumptions, endpoint-specific sample size, missing-data handling, and numerical estimates are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or how multiple hypotheses or repeated measurements were handled. Because the study description includes several broad aims and mentions DNA injury, signaling pathways, and other types of damage, it is not possible to determine from the record whether additional outcomes were assessed or whether any multiplicity adjustment was planned.
In general, testing many outcomes or many comparisons can increase the chance of observing at least one apparently unusual result by chance. Methods for addressing multiplicity depend on the number and role of tests and on whether a primary outcome was specified in advance. The registry identifies a primary endpoint, but does not describe multiplicity procedures. No adjustment should be assumed.
The record lists enrollment of 60, but does not state how many participants had evaluable primary endpoint measurements. It does not report missing endpoint values, reasons for missingness, exclusions, or whether any imputation or other missing-data method was used. It also does not define an analysis population, such as all enrolled participants or only those with complete measurements. General statistical interpretation depends on these details because missing observations can affect both the estimate and its uncertainty.
The registry’s safety information has a stated number at risk, but that does not identify the endpoint analysis population. The endpoint-specific denominator and analysis procedures are not reported in the registry record. Thus the completeness of the primary outcome data and the treatment of missing observations cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm 1 | 4 | 42 | 9.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1 | 0 of 42 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1 |
|---|---|---|
| Ruptured cerebral aneurysm | Vascular disorders | 1 of 42 |
| Ischemic colitis | Gastrointestinal disorders | 1 of 42 |
| Death | Cardiac disorders | 1 of 42 |
| Abdominal pain | Gastrointestinal disorders | 1 of 42 |
Serious events with the highest arm-level rate: ruptured cerebral aneurysm (2.4%), ischemic colitis (2.4%), death (2.4%), abdominal pain (2.4%).
The registry reports one safety group, labeled Arm 1, with 42 participants at risk for serious adverse events and 4 affected. It reports 42 at risk and 0 affected for other adverse events. These are registry safety counts; they are not primary endpoint results and should not be used to infer the number with evaluable biomarker measurements.
The listed serious adverse-event terms are Ruptured cerebral aneurysm, Ischemic colitis, Death, and Abdominal pain, each reported as 2.4%. These percentages are quoted as recorded. The registry does not provide event-level detail, timing, severity descriptions beyond the serious-event categorization, or an explanation of how the listed terms relate to the affected-participant count. A separate death count is not reported in the registry record, although Death appears among the listed terms.
In general, an adverse-event count records events or affected participants according to the reporting conventions used; those concepts are not always interchangeable. The registry’s figures should therefore be read as reported rather than recalculated or interpreted as comparative risks. With a single-group, non-randomized design and no separate control group, these safety counts do not support a like-for-like comparison between treatment groups.
12. What the Result Does, and Does Not, Mean
The record describes a study of bile acids, oral UDCA, and a biomarker of DNA damage in patients with Barrett’s esophagus. It identifies p-H2AX levels after DCA perfusion, following 8 weeks of UDCA treatment, as the primary endpoint. The stated outcome is a change in relative densitometry units, summarized as a mean with standard error.
What the registry does not provide is the observed mean, the amount or direction of change, the endpoint-specific sample size, an uncertainty interval, or a test result. It therefore does not show whether p-H2AX levels changed, how large any change was, or how precisely it was estimated. The endpoint’s proposed protective interpretation is a rationale, not a finding.
The study is non-randomized, single-group, and unmasked. In general, that design can describe measurements across a treatment and perfusion sequence, but it cannot provide the same controlled comparison as random assignment to concurrent groups. Any observed pattern would need to be interpreted in light of that structure, as well as the measurement process and any missing observations. Those details are not fully reported.
The registry’s listed enrollment does not establish the number included in the primary endpoint analysis. The separate safety counts give information about reported adverse events, but they do not answer the biomarker question. Likewise, the presence of a planned outcome description does not substitute for results.
The defensible conclusion is narrow: the registry records a biological question and study procedure, but the primary numerical result and analysis are not reported in the registry record. It is not possible to determine from this information whether the hypothesized pattern occurred, nor to make a claim about the magnitude or statistical significance of an endpoint effect.
13. Why This Trial Matters Statistically
This study illustrates why a clear endpoint description is not the same as a report of results. The registry explains that p-H2AX is used as a measure of DNA damage and identifies the tissue population and treatment context. Those details help readers understand what the investigators intended to measure. Without the observed values and analysis, however, readers cannot assess the estimated change or its precision.
The design also makes the comparison question important. A single-group sequence can provide observations before and after procedures or treatment, but the interpretation of a change depends on whether the comparison is within participants and how the analysis accounts for that relationship. It also depends on what alternative explanations remain without a concurrent control group. The registry’s design labels make these constraints visible even though the analysis itself is not reported.
The record further distinguishes enrollment from endpoint information. An enrollment count alone cannot show how many participants contributed tissue measurements, how many observations were missing, or whether the analyzed group differed from those enrolled. Those details are essential for understanding the denominator and precision of a continuous biomarker result.
Finally, the registry includes safety counts alongside a biological endpoint, but the two types of information answer different questions. Safety event counts do not provide evidence about the p-H2AX outcome. Keeping endpoint results, study design, and safety reporting separate is central to accurate statistical interpretation.
For biostatisticians and clinical researchers, this case highlights the value of reporting numerical estimates, uncertainty, analysis methods, and analysis populations together. Those elements allow readers to distinguish a stated hypothesis from an observed result and to judge what the design can support.
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 principal limitation of the registry information is that it does not report numerical results or an analysis for the primary endpoint. The mean p-H2AX level, change in relative densitometry units, standard error, confidence interval, and statistical test result are not reported in the registry record. Effect magnitude and precision therefore cannot be evaluated.
The design is non-randomized, single-group, and unmasked. There is no separate control group described for a like-for-like comparison. As a result, any within-group change would need cautious interpretation because the design does not, by itself, distinguish a treatment-related pattern from other changes associated with time, perfusion, or measurement. The registry does not report methods to address these possibilities.
The endpoint population is restricted to metaplastic epithelium. The registry states that squamous epithelium was not evaluated, following in vitro findings that DCA exposure did not cause DNA damage in those cells. Consequently, the primary endpoint description does not cover that tissue type. The registry also does not provide the number of participants or samples contributing to the endpoint, or describe missing measurements and exclusions.
The arm description gives a sequence of perfusions and oral UDCA treatment, but the record does not report detailed timing or measurement procedures beyond the stated sequence and endpoint timeframe. The statistical test, model, analysis population, multiplicity handling, and missing-data approach are also not reported. These omissions prevent independent assessment of the assumptions behind any endpoint estimate.
Finally, the record’s planning assumptions refer to equal allocation between two arms, whereas the listed design is single-group and non-randomized. The assumptions are described as a planning illustration, not as the trial’s own design justification. The registry does not report a sample-size justification for the actual study design.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Studies on Bile Acids in Barrett's Esophagus — NCT00858858.
- Registry record last updated 2015-04-30; status last verified 2015-04.
- Results first posted 2014-11-24.
- 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.
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18. Record Summary
NCT00858858 is a completed, non-randomized, unmasked, single-group study titled “Clinical Studies on Bile Acids in Barrett’s Esophagus.” The registry lists enrollment of 60, the US Department of Veterans Affairs as sponsor, and study dates of 2009-03 to 2013-03. The listed phase is NA.
The arm description includes DCA and UDCA esophageal perfusions, oral UDCA at 10 mg/kg qd for 8 weeks, and a final DCA perfusion. The primary endpoint is the change in p-H2AX levels, in relative densitometry units, after 8 weeks of UDCA treatment. Only metaplastic epithelium was evaluated.
The registry lists one outcome measure and zero analyses. Numerical primary endpoint results, endpoint-specific sample size, and statistical analysis details are not reported in the registry record. Safety reporting lists 42 at risk and 4 affected by serious adverse events, and 42 at risk and 0 affected by other adverse events.