Efficacy of Brooke Bond Black Tea Extract on Flow Mediated Dilation in Indian Males: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Brooke Bond Black Tea Extract on Flow Mediated Dilation in Indian Males (NCT01561300), a randomized na study. The primary outcome is 'Acute-upon-chronic Effect' of Tea vs Control.

2. Clinical Question

3. Trial Design

The registry describes a randomized, quadruple-masked, crossover study of nutrition interventions in healthy adult Indian males. Enrollment was 30, and the study is marked completed. The listed interventions were a black tea extract and a control. The trial title and summary specify an interest in flow-mediated dilation after an acute dose and after one week of consumption. The stated extract dose was 1800 mg/day, equivalent to 400 mg flavonoids.

A crossover design means that participants receive interventions in a sequence, so within-participant comparisons may be possible. This general feature can reduce the influence of stable differences between participants, but it does not by itself guarantee that periods are comparable. The sequence, period structure, washout arrangements, and handling of possible carryover effects are not reported in the registry record. The registry labels the study quadruple-masked but does not explain which groups of people were masked.

The primary outcome timeframe was baseline day 1 to 2 hours after consumption on day 8. The primary title calls the contrast an “acute-upon-chronic” effect, while the listed timeframe describes a day-8 measurement following a baseline on day 1. The registry also lists acute and chronic tea-versus-control comparisons as secondary outcomes. Results for those comparisons are not available as estimable two-arm continuous comparisons in the posted record.

Enrollment and the analyzed primary population should not be treated as interchangeable. The primary description refers to a per-protocol population and mentions one subject who did not produce relevant data, three subjects removed during blind review, and single data points removed for six subjects. The description ends before the reasons for all data-point removals are fully stated. The detailed participant flow and the relationship between the enrollment figure and the analysis populations are not reported in the registry record.

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: Thirty subjects meeting all criteria were randomised over the two arms

Run in on Placebo

Reasons for not completing this period:

First Intervention

Washout on Placebo

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Per protocol based on the full data set excluding one subject who did produce relevant data (AE) and three subjects who were removed during blind review (operator comments, hypertension and increase in body weight). Single data points were removed for 6 subjects (all single data points) based on operator comments.

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 'Acute-upon-chronic Effect' of Tea vs Control, measured over Baseline day 1 to 2 hours post consumption on day 8..

Flow-mediated dilation (FMD) is a measure of the change in artery diameter following a brief period of reduced blood flow and the subsequent return of flow. In this study, a baseline artery diameter was measured, the forearm was occluded, and a post-release scan was used to identify the maximal increase above baseline. The endpoint is expressed as percentage of change in diameter.

FMD is used as a physiological measure of blood-vessel response to reactive hyperaemia. As a continuous measure, it can capture differences across a range of values rather than assigning participants to outcome categories. That can make the estimated group contrast and its uncertainty more informative than a simple count of participants meeting a threshold. This is a general statistical explanation, not a claim about the clinical meaning of any particular FMD value.

The primary endpoint is titled “acute-upon-chronic Effect” of tea versus control. Its stated timeframe is baseline day 1 to 2 hours post consumption on day 8. The primary description says the outcome concerns change in FMD due to tea compared with control, but the posted model is labeled as a mean difference in final values. The record therefore gives a final-value contrast alongside a timeframe that refers to change from baseline. How baseline measurements were incorporated into the model is not reported in the registry record.

The registry reports least-squares means with 95% confidence intervals for the intervention arms. These model-based summaries and the mixed-model contrast are the relevant posted statistical results; the record does not establish that the arm summaries alone reproduce the full model analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome and a mixed-model analysis. Several statistical ideas help interpret the posted estimate, but the exact model specification and analysis plan are not reported in the registry record.

What does the estimate describe?

A mean difference expresses a contrast between group means on the scale of the outcome. Here the reported parameter is “Mean Difference (Final Values),” and the estimate is -1.00. The arm summaries are least-squares means, which are model-based means rather than necessarily raw arithmetic averages. In general, least-squares means can reflect the structure and terms in a fitted model. The registry does not state enough detail to determine precisely how these means were adjusted or how the crossover structure entered the model.

The primary endpoint description refers to change in FMD, while the analysis parameter refers to final values. A final-value comparison and a comparison of change from baseline are different estimands in general. A model can account for baseline in several ways, but the chosen method cannot be inferred from the endpoint wording. How baseline entered the reported mixed model is not reported in the registry record.

How should the confidence interval be read?

A confidence interval expresses uncertainty around an estimate under the statistical model and its assumptions. The reported 95% confidence interval for the mean difference runs from -2.16 to 0.17. In general, a wider interval indicates less precision than a narrower interval. This interval includes values consistent with a difference in either direction, so the posted estimate should not be read as a highly precise determination of the contrast. The interval is not a range that is guaranteed to contain the true value, and it does not describe the spread of individual participant measurements.

The confidence intervals around the arm-level least-squares means describe uncertainty for each mean. They are not interchangeable with the confidence interval for the difference. The model-based contrast is the direct inferential comparison reported by the registry, and its interval should be used to understand uncertainty in that contrast.

What does the p-value contribute?

The p-value of 0.09 is calculated under a null model and other assumptions of the analysis. In general, it indicates how often data at least as incompatible with the null model would arise if that model and its assumptions held. It does not measure effect size, clinical importance, or the probability that a hypothesis is true. The p-value should be interpreted together with the point estimate, interval, design, population and analysis details.

The registry does not report the primary analysis threshold or a complete statistical analysis plan. A significance level of 0.05 appears among the sample-size planning assumptions, but that is not evidence that the same threshold governed the reported analysis. Conclusions based only on whether a p-value is above or below a conventional cutoff would discard information conveyed by the estimate and interval.

Why does the crossover design matter?

In general, crossover studies compare interventions within the same participants across different periods. This can account for some stable differences between people, but outcomes may also depend on period, order, or lingering effects of an earlier intervention. A mixed model can be used for correlated observations and other design features, but its appropriateness depends on how it is specified. The record identifies a mixed-model analysis without reporting the model terms, sequence allocation, period handling, or carryover assessment. Those aspects cannot be evaluated from the posted description.

Over-dispersion is a concern for some count outcomes when variability exceeds what a simple count model assumes. It is not the central issue for this continuous FMD outcome. For continuous outcomes, the distribution of residuals, correlation structure, and model fit may matter; their diagnostics are not reported in the registry record. This is a general distinction and does not imply that any particular model assumption was violated in this study.

What do the sample-size assumptions mean?

The registry describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such illustrations are hypothetical planning calculations, not observed power and not evidence that the original trial was designed using those assumptions. They also do not establish that a target effect is clinically important. The planning assumptions and any illustration values should be distinguished from observed trial results.

The registry does not report a sample-size justification for the original study, the assumptions used in its design, or whether any interim analyses were planned or conducted. No complete statistical analysis plan is reported. The listed enrollment and analyzed population do not by themselves reveal whether the study was adequately powered for its intended question.

10. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using a mixed-model approach. Its stated parameter is the mean difference in final values, estimated as -1.00, with a 95% confidence interval from -2.16 to 0.17 and p = 0.09. The arm estimates are least-squares means. These are the posted model-based results and should be kept distinct from any simple recalculation based only on summary statistics.

The registry does not flag a discrepancy between the sponsor analysis and a recalculation. No recalculated contrast or inferential result is stated in the registry record, so there is no additional recalculated number to compare with the sponsor estimate. The model-based result is especially relevant because the study is described as crossover and the analysis as mixed models; simple calculations from arm summaries would not necessarily account for the within-participant structure or other model terms.

The record does not report the full model specification, covariates, or handling of period and sequence. Those omissions limit independent assessment of how the sponsor analysis was constructed. The reported result can be described, but its model details cannot be reconstructed from the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary acute-upon-chronic tea-versus-control outcome and two secondary outcomes: acute effect of tea versus control and chronic effect of tea versus control. It reports three outcome measures and three analyses overall. For two-arm continuous comparisons, the registry indicates that values are missing or not estimable. Thus, the two secondary comparisons cannot be interpreted from numerical estimates, confidence intervals or p-values in the posted record.

When a study examines multiple outcomes or comparisons, the chance of obtaining an apparently notable result can increase if each is assessed separately. Statistical approaches to multiplicity may adjust thresholds or otherwise account for the family of analyses. Whether such an approach was planned or used is not reported in the registry record. The number of listed outcomes alone does not establish that a multiplicity adjustment was required, nor does it show that one was or was not performed.

The full statistical analysis plan, the pre-specified hierarchy of outcomes, and any rules for handling multiple comparisons are not reported in the registry record. The primary result should therefore be read as the posted estimate for its named comparison, without assuming that it was adjusted for the secondary outcomes or that it was selected according to a documented hierarchy.

The primary analysis population is described as per protocol. The record mentions one subject who did not produce relevant data, three subjects removed during blind review for operator comments, hypertension and increase in body weight, and single data points removed for six subjects. The available description is truncated after beginning to explain the basis for those data-point removals. The complete reasons, timing, and statistical handling of missing observations are not reported in the registry record.

In general, exclusion of participants or individual observations can affect both the analysis population and the estimate, particularly if missingness or exclusion is related to outcomes. The registry does not provide enough detail to assess that possibility. It also does not report a complete intention-to-treat analysis or a sensitivity analysis for missing data. The stated per-protocol result should not be assumed to represent every enrolled participant.

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.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for Tea Extract, Control and Placebo groups. The serious-event counts are zero for each listed group. The numbers at risk are 29 for Tea Extract, 29 for Control and 30 for Placebo. These are the registry’s reported group figures; the record does not explain the relationship of the Placebo category to the two listed primary intervention arms.

The absence of reported serious events in these groups is a descriptive finding, not proof that serious harms cannot occur. In general, uncommon events may not appear in a study of limited size, and a group-level count does not establish comparative safety. The registry does not report event definitions, severity details beyond the serious category, exposure-adjusted rates, or a statistical comparison of serious events.

For other adverse events, the registry reports one event in Tea Extract, one in Control and three in Placebo. The corresponding numbers at risk are 29, 29 and 30. No serious adverse event terms are listed. Death counts are not reported in the registry record. These figures should be interpreted as recorded event counts, not as a complete assessment of safety or as evidence that one intervention is safer than another.

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

The posted primary result is an estimate of the tea-versus-control contrast in final FMD values for the acute-upon-chronic comparison. The mixed-model mean difference is -1.00, with a 95% confidence interval from -2.16 to 0.17 and p = 0.09. The interval spans values on either side of no difference, indicating uncertainty about both the direction and magnitude of the contrast. The arm-level least-squares means are 8.03 for Tea Beverage and 9.03 for Control Beverage, each with its own confidence interval.

This result does not establish that the interventions are equivalent. An interval that includes no difference is not evidence that every practically meaningful difference has been excluded. Equivalence or non-inferiority requires specified margins and an analysis designed for that purpose; those are not reported in the registry record. The p-value also does not establish the probability that the null hypothesis is true.

The result is specific to the population and analysis described in the record: healthy adult Indian males and a per-protocol primary analysis, with exclusions and data-point removals noted. It should not be generalized automatically to other populations, settings, interventions or durations. The available record describes the dose and the primary timeframe, but it does not provide enough information to assess all features of the crossover implementation or the mixed model.

The primary result also does not answer the separate secondary questions about acute and chronic effects. Numerical results for those two-arm continuous comparisons are missing or not estimable in the registry record. Nor should the outcome be treated as a direct measure of a clinical event or patient-important benefit: it is a physiological measure of artery diameter response. The clinical importance of the observed contrast is not established by the posted statistical result.

Finally, the safety figures are descriptive and do not support a broad conclusion about safety. Overall, the registry provides an imprecise model-based estimate for the named FMD comparison, while important details about analysis, missing data, multiplicity and the crossover structure are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its design and outcome invite several distinctions that are easy to overlook. It is randomized and crossover, but the primary reported contrast is a mixed-model comparison of final values. Understanding how a crossover design was represented in the model requires information about periods, sequences and within-participant correlation that is not reported in the registry record.

The endpoint description concerns change in FMD, while the reported analysis parameter is mean difference in final values. That difference in wording illustrates why an estimand should be read carefully: a change contrast and a final-value contrast are not necessarily the same analysis. The record does not state how baseline values entered the model, so the distinction cannot be resolved from the posted description.

The result also shows why a point estimate alone is not enough. The mean difference is -1.00, but its 95% confidence interval extends from -2.16 to 0.17. The uncertainty interval provides a more complete account of precision than the point estimate, while the p-value of 0.09 does not by itself convey the range of plausible effects or their importance.

Finally, the record distinguishes a per-protocol primary analysis from overall enrollment and notes exclusions and data-point removals. This highlights the need to understand which observations contributed to an estimate, how missing data were handled, and whether sensitivity analyses support the result. The trial matters statistically as a case where reporting design, model specification and analysis-population details are central to interpreting an otherwise straightforward group contrast.

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 does not provide a complete statistical analysis plan or a full specification of the mixed model. The model terms, covariance structure, baseline adjustment, and handling of period and sequence are not reported. Without these details, the crossover analysis cannot be independently reconstructed from the record.

The primary endpoint wording refers to change in FMD, while the reported parameter is a mean difference in final values. The record does not explain how the analysis connects those descriptions. The primary population is labeled per protocol, but the available description of exclusions and removed data points is incomplete. The reasons for all single-point removals and the handling of missing observations are not fully reported.

The two secondary outcomes are listed, but their two-arm continuous comparisons are marked as missing or not estimable. The registry does not report the multiplicity strategy, if any, or a hierarchy for interpreting these outcomes. It also does not report the original sample-size justification, the design assumptions used for that justification, or interim analyses.

The registry’s adverse-event categories include a Placebo group in addition to Tea Extract and Control, but the relationship of that category to the primary comparison is not explained. Event details and death counts are not reported in the registry record. The reported event counts therefore offer only a limited descriptive view of safety.

These limitations concern reporting and interpretation; they do not show that a particular design or analysis choice was inappropriate. They do mean that the precision, robustness and generalizability of the posted result cannot be fully assessed from the registry record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy of Brooke Bond Black Tea Extract on Flow Mediated Dilation in Indian Males — NCT01561300.
• Registry record last updated 2017-04-05; status last verified 2017-02.
• Results first posted 2017-04-05.
• 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 describes a completed, randomized, quadruple-masked crossover study of standardized Brooke Bond black tea extract in healthy adult Indian males. Enrollment was 30. The intervention is described as 1800 mg/day, equivalent to 400 mg flavonoids, and the primary outcome is flow-mediated dilation after consumption on day 8.

The primary result is a mixed-model mean difference in final values of -1.00, with a 95% confidence interval from -2.16 to 0.17 and p = 0.09. The record also lists two secondary outcomes, but their two-arm continuous results are missing or not estimable. The primary population is described as per protocol, with exclusions and data-point removals noted but not fully detailed.

Important details about the model, crossover periods, missing-data handling, multiplicity and original sample-size justification are not reported in the registry record. The posted estimate should therefore be read as a specific, uncertain result rather than a complete account of the study’s design and analysis.