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 Anthocyanin Extract and Phospholipid Curcumin in Colorectal Adenoma (NCT01948661), a randomized na study. The primary outcome is Change in Beta Catenin Expression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01948661 |
| Phase | NA |
| Condition | Colorectal Adenoma, Risk Reduction |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ente Ospedaliero Ospedali Galliera |
| Results posted | Yes |
2. Clinical Question
Population
Participants with colorectal adenoma were enrolled in a window-of-opportunity trial before endoscopic polypectomy. The registry record lists an enrollment of 45. The primary outcome description concerns beta-catenin expression in normal tissue and dysplasia, with expression considered according to treatment arm and time point.
Intervention
The experimental arm received Mirtoselect and Meriva, described as anthocyanins plus phospholipidic curcumin. The regimen is listed as Mirtoselect 500 mg tablets, 1000 mg per day, and Meriva 500 mg tablets, 1000 mg per day, for 28 days. These are the intervention details in the registry record, not evidence about adherence or exposure actually achieved.
Comparator
The control arm received placeboA plus placeboB per day for four weeks. The registry record does not give further details about the placebo ingredients or whether the placebo preparations were matched in appearance or taste.
Primary question
The stated primary question is whether beta-catenin expression changes between baseline and 4 weeks in normal and adenomatous colonic tissue, in relation to the assigned treatment. The measure is the percentage of positive cells. The record does not report a single treatment-effect estimate or an analyzed comparison for this outcome, so the direction and precision of any between-arm difference cannot be assessed from the registry results.
The brief description frames the study as a comparison of the combination with placebo during a four weeks intervention before polypectomy. It also notes prior claims of anticancer effects for curcumin and cyanidin-3-glucoside. Those background statements are the study rationale; they are not trial findings. The registry record identifies change in biomarker expression as a secondary outcome, but does not report its results either.
3. Trial Design
This was a randomized, parallel-group trial with quadruple masking, listed as phase NA. Its official title describes it as a randomized window-of-opportunity trial in subjects with colorectal adenoma. A window-of-opportunity design places an intervention in a defined period before a planned clinical procedure; in this record, the brief description identifies endoscopic polypectomy and an intervention lasting four weeks. The registry lists the trial status as completed, an enrollment of 45, a start of 2014-03, and primary completion on 2019-01-31.
Participants were allocated to an experimental arm receiving anthocyanin extract plus phospholipid curcumin or a control arm receiving placebo preparations. The listed experimental regimen was two oral Mirtoselect tablets per day, totaling 1000 mg, and two oral Meriva tablets per day, totaling 1000 mg, for 28 days. The placebo arm is described as placeboA plus placeboB per day for four weeks. The record does not report the method used to generate the random sequence, allocation concealment procedures, or the identities of the groups included in quadruple masking. Those details should not be inferred from the design labels.
A parallel design means the assigned groups are followed as separate groups rather than each participant receiving both regimens in sequence. Random allocation is intended, in general, to reduce systematic differences between groups at assignment, although it cannot guarantee balance in a small trial. The registry record does not describe baseline characteristics or provide the analyzed numbers for the primary endpoint. It lists colorectal adenoma and risk reduction as conditions, and names Ente Ospedaliero Ospedali Galliera as sponsor. The record does not report additional protocol details that would clarify implementation, adherence, or the timing of tissue collection beyond baseline and 4 weeks.
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: 53 participants were contacted: * 8 refused to participate, * 45 signed the Informed Consent: 10 were not eligible and 35 were randomized
Overall Study
| Stage | Experimental: Anthocyanins+Phospholipidic Curcumin | Placebo Comparator |
|---|---|---|
| STARTED | 17 | 18 |
| COMPLETED | 15 | 14 |
| NOT COMPLETED | 2 | 4 |
Reasons for not completing this period:
| Reason | Experimental: Anthocyanins+Phospholipidic Curcumin | Placebo Comparator |
|---|---|---|
| Withdrawal by Subject | 2 | 4 |
Analysis population for the primary outcome, as defined in the registry: Beta-catenin expression according to the treatment arms and the time points in normal tissue and dysplasia
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 | Experimental Arm | Control Arm | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 14 | 29 | |
| Age, Continuous | years | 70.8 (SD 9.8) | 67.9 (SD 10.8) | 69.3 (SD 10.3) |
| Sex: Female, Male: Female | Participants | 5 | 7 | 12 |
| Sex: Female, Male: Male | Participants | 10 | 7 | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 15 | 14 | 29 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Level of Education: Primary-middle | Participants | 5 | 6 | 11 |
| Level of Education: High university | Participants | 10 | 8 | 18 |
| Smoker: No | Participants | 4 | 5 | 9 |
| Smoker: Former | Participants | 8 | 7 | 15 |
| Smoker: Yes | Participants | 3 | 2 | 5 |
| Alcholol Habits: No | Participants | 5 | 7 | 12 |
| Alcholol Habits: Current/Former | Participants | 10 | 7 | 17 |
| Baseline BMI: <25 kg/m^2 | Participants | 7 | 9 | 16 |
| Baseline BMI: ≥25 kg/m^2 | Participants | 8 | 5 | 13 |
| Family history of colorectal cancer: No | Participants | 10 | 7 | 17 |
| Family history of colorectal cancer: Yes | Participants | 5 | 7 | 12 |
| Baseline histological type: Tubular | Participants | 10 | 10 | 20 |
| Baseline histological type: Villous | Participants | 5 | 4 | 9 |
| Baseline Dysplasia grade: Low-grade | Participants | 12 | 9 | 21 |
| Baseline Dysplasia grade: High-grade | Participants | 3 | 5 | 8 |
| # of comorbidity | number of comorbidities | 1 (0 to 3) | 2 (1 to 3) | 2 (1 to 3) |
| # of concomitant medications | number of concomitant medications | 2 (0 to 4) | 4 (2 to 5) | 3 (1 to 5) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Beta Catenin Expression, measured over baseline and 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of positive cells |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in beta-catenin expression, measured as the percentage of positive cells. The registry describes immunohistochemical expression in normal and adenomatous colonic tissue and identifies baseline and 4 weeks as the measurement time points. The outcome is specified as a continuous measure summarized by a mean and standard deviation. These are the planned measurement and summary characteristics; the registry record does not report the observed means, standard deviations, changes, or treatment comparisons.
Beta-catenin expression is used as a tissue biomarker. In general, a biomarker endpoint can capture a biological measurement within the study period without itself establishing a longer-term clinical outcome. Tissue assessment before polypectomy suits the stated window-of-opportunity setting because the trial is organized around measurements before a planned procedure. The record does not provide a rationale linking a particular change in this marker to a clinical benefit, nor does it report validation of the measurement for predicting later outcomes.
The endpoint description includes treatment arms, time points, and both normal tissue and dysplasia. That structure yields more than one potential outcome comparison. The registry record does not reduce these categories and time points to one reported result, and it does not identify a particular tissue type or time-point contrast as the sole analyzed comparison. Therefore, the endpoint definition can be described, but its observed treatment effect and precision cannot be reconstructed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is that the registry record gives the primary outcome definition but no analyzed primary-outcome values. It states that beta-catenin expression is assessed as the percentage of positive cells at baseline and 4 weeks in normal and adenomatous tissue. It does not give arm-specific means, standard deviations, changes from baseline, a between-arm contrast, a confidence interval, or a p-value. Consequently, the record does not establish the direction, magnitude, or statistical precision of a treatment comparison for beta-catenin expression.
The record lists 45 participants enrolled, but that enrollment figure alone does not establish how many contributed data to each tissue, time point, or analysis. The adverse-event entries separately list 15 participants at risk in the experimental arm and 14 in the control arm for the reported event categories. These figures should not be treated as the analyzed sample sizes for the primary endpoint. The record does not explain the relationship between enrolled participants and the numbers contributing to each endpoint analysis.
The endpoint spans several dimensions: assigned treatment, time, and tissue category. A change within one arm is not the same quantity as a difference in change between arms. In general, a treatment comparison should distinguish change over time in the intervention group from the corresponding change in the comparator group. The registry’s description does not present those quantities, nor does it specify which tissue and time-point comparison was selected for a main inference. No conclusion about a treatment effect can therefore be drawn from the endpoint description alone.
The record lists change in biomarker expression as a secondary outcome and reports two outcome measures, but it lists zero analyses. It does not give a hierarchy among outcomes, a statistical analysis plan, or a prespecified adjustment for multiple comparisons. This absence matters because examining several outcomes or endpoint dimensions can make an isolated result harder to interpret. It does not establish that any particular analysis was or was not performed outside the registry record; it means those details are not reported in the registry record.
The completion status indicates that the trial is recorded as completed, not that outcome data are available in the registry. A completed study can have an endpoint definition without a posted analysis. Here, the appropriate reading is limited to the design, outcome specification, and available safety counts. No estimate of efficacy, no evidence of equivalence, and no evidence of absence of an effect can be inferred from missing primary results. The same restraint applies to the secondary outcome.
The sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration is not a report of observed power and does not substitute for the trial’s analysis. The registry record does not report the trial’s own sample-size justification. Since the outcome estimates needed to interpret an observed effect are not reported in the registry record, the planning illustration should be understood as a design aid rather than evidence about what the trial found.
9. Statistical Methods Explained
The registry record identifies a continuous primary measure, a mean as its summary parameter, and standard deviation as its dispersion measure. It does not report the statistical analysis used to compare treatment groups. The explanations below are general descriptions of the relevant statistical ideas, not claims that a particular method was applied in this trial.
What does a mean describe?
In general, a mean summarizes the central value of a set of measurements by averaging them. For a continuous tissue measure such as percentage of positive cells, a group mean can provide a concise description of the measured expression. A mean alone does not show how variable individual measurements are, how many observations contribute, or how the distribution is shaped. That is why the registry specifies a standard deviation as a companion summary. The standard deviation describes the spread of individual observations around the mean; it is not the same as the uncertainty in the estimated mean or in a treatment contrast.
How should change over time be interpreted?
In general, a baseline-to-follow-up change can be summarized within each treatment group, but the within-group change is not by itself the treatment effect. A comparison between groups asks whether the change associated with one assignment differs from the change associated with the other assignment. An analysis may use change scores or account for the follow-up value while considering baseline measurements. Different approaches can produce different estimates, particularly when baseline values vary or when observations are incomplete. The registry record gives the measurement times as baseline and 4 weeks but does not report which approach was used.
The endpoint also identifies normal tissue and dysplasia. These categories should be treated as distinct parts of the outcome description unless an analysis plan explains otherwise. In general, results from different tissue types need not have the same distribution or treatment contrast. Combining them without a stated rationale could obscure differences; analyzing each separately creates more comparisons to interpret. The registry record does not identify a primary tissue-specific contrast, explain any pooling, or report separate results.
What does a confidence interval communicate?
In general, a confidence interval expresses the uncertainty around an estimated quantity, such as a mean difference between treatment groups. A narrower interval indicates greater precision under the assumptions of the analysis, while a wider interval indicates less precision. The interval is useful alongside the point estimate because a p-value alone does not show the range of effect sizes compatible with the data. No confidence interval or treatment-effect estimate for the primary endpoint is reported in the registry record, so neither the direction nor precision of the comparison can be assessed.
What does a p-value communicate?
In general, a p-value describes how compatible observed data are with a specified null model, under assumptions of the analysis. It does not measure the probability that the null hypothesis is true, the size of an effect, or its clinical importance. Interpretation depends on the outcome definition, comparison, model, and handling of multiplicity and missing data. The registry record does not report a primary-outcome p-value or the analysis model used to generate one.
Why can multiple comparisons matter?
In general, when an analysis examines multiple outcomes, time points, or subgroups, the chance of finding at least one apparently notable result by chance can rise if each comparison is treated as an independent primary test. Statistical plans may address this through a hierarchy of outcomes or an adjustment procedure. The record describes treatment arms, baseline and follow-up, normal tissue and dysplasia, and a secondary biomarker outcome. It does not report a multiplicity strategy or identify how these dimensions were handled. No specific correction should be presumed.
What does the planning illustration mean?
The record’s sample-size assumptions describe an illustration computed from an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The assumed effect to detect is a stated fraction of the observed effect. In general, a planning calculation asks how many participants per arm might be needed to detect a chosen effect under stated assumptions. It is conditional on those assumptions and is not an estimate of what the study observed. It is also not observed power, which is not an appropriate substitute for reporting an effect estimate and its uncertainty. The record does not report the trial’s own sample-size justification.
For continuous outcomes, planning calculations commonly depend on the assumed variability as well as the effect to detect. A normal approximation is a simplifying assumption about the distribution of an estimate or test statistic; its adequacy depends on the data and design. The registry record does not report the inputs used for the trial’s original design, any evaluation of distributional assumptions, or a sensitivity analysis. The planning assumptions alone do not establish that the trial was adequately sized for its primary endpoint.
What can randomization and masking establish?
In general, random allocation helps avoid systematic assignment based on participant characteristics, while masking can reduce some forms of bias in treatment delivery, assessment, or reporting. The registry labels the allocation randomized and the masking quadruple. Those labels do not reveal the sequence-generation process, allocation concealment, or which roles were masked. The registry record does not report those implementation details. Design labels should therefore be read as classifications, not as a complete description of safeguards.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome description contains several potential comparisons: treatment arms, baseline and 4 weeks, and normal tissue and dysplasia. A secondary outcome is also listed as change in biomarker expression. The registry record gives no analysis hierarchy, no identification of a single primary contrast among these dimensions, and no multiplicity procedure. Without those details, it is not possible to determine whether a reported result would represent a prespecified primary comparison or one among several examined comparisons. No primary or secondary analyses are posted in the registry record.
The record does not report missing-data counts, reasons for missingness, or the method used to handle missing observations. It also does not specify analysis populations, such as whether analyses were based on all randomized participants, participants who completed treatment, or participants with available tissue measurements. These are important details for a before-and-after tissue endpoint, because the amount and pattern of available data can affect the analysis and its interpretation. The enrollment figure does not establish how many observations were available for each tissue and time point.
The registry record also does not describe any statistical analysis plan, model specification, imputation procedure, or sensitivity analysis. These details are not reported in the registry record. Their absence prevents assessment of how multiplicity and incomplete data were addressed, but it does not show that no plan or analysis existed outside the registry.
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 |
|---|---|---|---|
| Experimental Arm | 0 | 15 | 0.0% |
| Control Arm | 0 | 14 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Experimental Arm | 0 of 15 |
| Control Arm | 0 of 14 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Experimental Arm | 3 of 15 |
| Control Arm | 2 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Experimental Arm | Control Arm |
|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | 1 of 15 | 1 of 14 |
| Stomach pain | Gastrointestinal disorders | 0 of 15 | 1 of 14 |
| Nausea | Gastrointestinal disorders | 1 of 15 | 0 of 14 |
| Diarrhea | Gastrointestinal disorders | 1 of 15 | 0 of 14 |
The registry lists serious adverse events for 15 participants at risk in the experimental arm and 14 in the control arm. Serious events affected 0 participants in each arm. Other adverse events affected 3 participants in the experimental arm and 2 in the control arm. Deaths are listed as 0 in both arms. These are the counts recorded for the listed groups, not estimates of a treatment effect.
Counts should be interpreted with their denominators and reporting context in mind. The registry gives the at-risk counts for these categories, but it does not describe event severity beyond the serious-versus-other distinction, event timing, recurrence, attribution, or whether a participant could have more than one event. The record lists no top serious-event terms. That does not establish that no events occurred beyond the categories summarized; it means no such terms are listed in the registry record.
The at-risk counts for adverse events should not be assumed to equal the number enrolled or the number included in the primary endpoint analysis. The registry does not explain any difference between these populations. These entries describe the posted safety counts only and do not support a broader conclusion about comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record allows a reader to identify the study question, the randomized comparison, the planned tissue biomarker, and the short intervention period before polypectomy. It also supplies basic design information and adverse-event counts. It does not, however, report analyzed results for the primary outcome. There are no posted arm-specific beta-catenin values, changes, treatment-effect estimates, confidence intervals, or p-values. The direction and precision of the primary comparison are therefore unknown from the registry record.
That distinction is important: a defined endpoint is not a result. Likewise, a completed trial status does not mean that its outcome data or statistical analysis are posted. Without the primary comparison, the registry does not show whether expression changed in either group, whether changes differed between groups, or how uncertain any estimate might be. Missing results should not be interpreted as evidence that the treatment had no effect, nor as evidence that it had an effect.
The endpoint is a measurement of beta-catenin expression in tissue at baseline and 4 weeks. In general, changes in a biomarker are not automatically equivalent to changes in a clinical outcome. The registry record does not report a relationship between this measurement and later clinical outcomes, nor does it provide follow-up findings beyond the stated endpoint time. The trial description therefore supports an account of the question and measurement, but not a conclusion about clinical benefit or harm.
The posted safety counts offer a limited description: serious adverse events and deaths are listed as 0 in both groups, while other adverse events are listed for 3 participants in the experimental arm and 2 in the control arm. Those figures do not provide event details or a complete comparative safety analysis. The appropriate interpretation remains bounded by what the record actually reports, including the absence of a primary-outcome analysis.
13. Why This Trial Matters Statistically
Statistically, this trial is a useful example of why design information and outcome results must be read separately. The record describes randomization, parallel groups, quadruple masking, a continuous primary biomarker, and repeated measurement before a planned procedure. Those features identify the broad framework for comparing groups. They do not supply the treatment-effect estimate needed to evaluate the primary question. A completed status and a clearly named outcome cannot substitute for analyzed data.
The endpoint has several dimensions: time, tissue category, and treatment assignment. That structure raises practical questions about which contrast is primary, whether different tissue categories are analyzed separately, and how multiple comparisons are handled. The record does not answer those questions. Making them explicit helps readers distinguish a single prespecified inference from exploratory findings and understand what a reported estimate would represent.
The registry’s planning assumptions also illustrate the difference between design calculations and observed evidence. A planning illustration depends on assumptions about effect size, allocation, significance level, and approximation. It cannot show what the trial found or how precise an observed comparison is. The actual outcome analysis and its uncertainty are essential for interpreting the evidence, and those results are not reported in the registry record.
Finally, safety counts require a denominator and context, while outcome analyses require clarity about who contributed data and how missing measurements were handled. Here, the record posts some adverse-event counts but does not describe analysis populations or missing-data methods for the primary biomarker. The trial therefore highlights a broader statistical reading principle: understanding a clinical study requires the outcome estimate, its uncertainty, the analysis choices, and the population underlying the result, not design labels alone.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation for interpretation is that the registry record does not report the primary outcome analysis. Although beta-catenin expression, its measurement unit, and the time points are described, no observed summary or treatment comparison is available. This prevents assessment of effect direction, magnitude, or precision. The same absence applies to the listed secondary outcome of change in biomarker expression.
The outcome description includes normal tissue and dysplasia, as well as baseline and 4 weeks, but the record does not identify a single primary tissue-specific contrast. It does not explain whether results were intended to be combined or analyzed separately. There is no reported statistical plan to clarify the primary comparison, multiplicity handling, model, or treatment of missing observations. Analysis populations are also not reported.
The registry reports an enrollment of 45 but does not provide a participant flow or the number contributing measurements at each endpoint category and time point. Adverse-event denominators are listed separately, and their relation to the primary endpoint population is not explained. The record does not report adherence, intervention exposure achieved, or reasons for missing data. These omissions limit the ability to connect the stated regimen with the data that might have been analyzed.
Other design details are also not reported in the registry record, including how the random sequence was generated, how allocation was concealed, and which roles were masked. The record does not provide additional placebo details. It lists the trial as completed, but completion status does not resolve these reporting gaps. These limitations concern what can be assessed from the registry record; they do not establish that the unreported procedures or analyses were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Anthocyanin Extract and Phospholipid Curcumin in Colorectal Adenoma — NCT01948661.
- Registry record last updated 2024-11-21; status last verified 2024-10.
- Results first posted 2024-11-21.
- 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
NCT01948661 is a completed randomized, parallel-group, quadruple-masked trial of anthocyanin extract plus phospholipid curcumin versus placebo in participants with colorectal adenoma. The record lists an enrollment of 45, phase NA, a start of 2014-03, and primary completion on 2019-01-31. The experimental regimen is described for 28 days before endoscopic polypectomy.
The primary outcome is change in beta-catenin expression, measured as the percentage of positive cells in normal and adenomatous tissue at baseline and 4 weeks. The record specifies a mean and standard deviation but does not report analyzed primary results. A secondary biomarker outcome is listed, with no analyses reported in the registry record. Safety entries list serious adverse events affecting 0 participants in each arm, other adverse events affecting 3 in the experimental arm and 2 in the control arm, and deaths listed as 0 in both arms.