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 Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males (NCT02214290), a randomized na study. The primary outcome is Aortic Blood Pressure.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02214290 |
| Phase | NA |
| Condition | Hypertension, Healthy |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Florida State University |
| Results posted | Yes |
2. Clinical Question
Population
The primary endpoint describes young, apparently healthy individuals aged 18-40 years old. The trial title specifies healthy males. The registry lists an enrollment of 16, but does not report participant-level characteristics or how many participants contributed data to each endpoint.
Intervention
The registry lists a 200 mg caffeine tablet and L-citrulline supplementation. The endpoint description concerns acute caffeine ingestion at rest and 30 minutes after ingestion, before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo.
Comparator
The listed comparator is a placebo pill; the registry also lists L-citrulline as an intervention. It does not fully specify the treatment sequence, period structure, or the precise contrast used for the primary analysis.
Primary question
The clinical question is how aortic blood pressure changes from rest to 30 minutes after caffeine ingestion, and whether that response differs after the listed 7-day L-citrulline or placebo period. The registry record does not report a single numerical comparison answering this question.
3. Trial Design
The registry identifies NCT02214290 as a completed randomized, double-blind, crossover trial sponsored by Florida State University. Its title concerns oral caffeine and L-citrulline supplementation and arterial function in healthy males. The record lists an enrollment of 16 and gives the study start as 2012-09 and primary completion as 2014-03. The phase is listed as NA.
The interventions are Caffeine, Placebo, and L-citrulline. The caffeine intervention is described as a 200 mg tablet produced by CVS Pharmacy, USA; the placebo as a pill produced by NOW FOODS, USA; and the L-citrulline intervention as a 750 mg capsule provided by NOW FOODS. The primary endpoint description frames assessment around an acute caffeine challenge before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo.
In general, a crossover design assigns participants to receive more than one condition over time, so within-participant comparisons can be relevant. Randomization and double masking describe features of the assigned design, but do not establish the sequence, concealment procedures, masking success, or timing of each period. The sequence, washout interval, and detailed conduct of the crossover are not reported in the registry record.
The registry also lists Hypertension and Healthy among the conditions, while the endpoint population is described as young, apparently healthy individuals. It does not report detailed eligibility criteria, recruitment procedures, baseline characteristics, or the number of participants analyzed for each endpoint. Those omissions limit how fully the design and analyzed population can be reconstructed from the 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: Of the 42 individuals screened, 16 individuals completed the intervention in its entirety.
First Intervention (7 Days)
| Stage | Citrulline First, Then Placebo | Placebo First, Then L-Citrulline |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Washout (14 Days)
| Stage | Citrulline First, Then Placebo | Placebo First, Then L-Citrulline |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Second Intervention (7 Days)
| Stage | Citrulline First, Then Placebo | Placebo First, Then L-Citrulline |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Young, apparently healthy individuals, aged 18-40 years old.
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 | L-Citrulline or Placebo |
|---|---|---|
| Participants analysed | 16 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 16 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 23 (SD 3) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 16 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 16 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Aortic Blood Pressure, measured over Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is aortic blood pressure, reported in mmHg as a mean with standard deviation. The registry describes measurements at rest and 30 minutes after acute ingestion of 200 mg of caffeine, both before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo. The stated timeframe is Baseline and Day 7, with a calculated change between rest and 30 minutes post-caffeine ingestion at those time points.
Aortic blood pressure represents pressure in the central arterial circulation. In general, measurements of central pressure can be used to characterize a cardiovascular response to an acute exposure, while comparing rest with a post-exposure measurement describes change over that short interval. The registry’s rationale discusses caffeine, blood pressure, arterial stiffness, pulse wave velocity, and wave reflection. These provide context for the endpoint, but do not establish what the trial found.
The record identifies the measure and timing but does not give the endpoint values, an estimated treatment contrast, uncertainty intervals, or a p-value. It also flags that the primary outcome has several categories or time points and was not reduced to one comparison. Thus, the endpoint definition is available, but a single numerical result for the primary question is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a question about the acute change in aortic blood pressure after caffeine, with measurements before and after a 7-day L-citrulline or placebo period. It does not provide numerical primary endpoint results. In particular, it does not report group means, standard deviations, a treatment contrast, a confidence interval, or a p-value for one selected comparison. The listed outcome therefore cannot be interpreted as evidence for the size, direction, or precision of an effect.
The registry indicates that the primary outcome spans several categories or time points and was not reduced to a single comparison. That matters because a result depends on which change, time point, and treatment contrast is being considered. Without a defined primary contrast and its estimate, a reader cannot tell whether the posted results favor one condition, how large any difference might be, or how compatible the data are with a range of effects.
In general, a confidence interval expresses uncertainty around an estimate and helps distinguish a precise estimate from one that is compatible with a broad range of values. A p-value addresses compatibility between observed data and a specified null model; it does not by itself describe the size or clinical importance of an effect. Neither type of inferential result is reported for the primary endpoint in this record, so no such interpretation can be made.
The design is described as randomized, double-blind, and crossover, but those labels alone do not resolve concerns about the analysis. The record does not describe the sequence of conditions, period-specific observations, handling of repeated measurements, or the model used for analysis. It also does not report the analyzed population or missing endpoint data. These details are needed to assess how the trial’s design was reflected in its analysis.
The registry lists zero values in the adverse-event fields for both listed groups, including the fields for serious and other events and deaths. The at-risk fields are also listed as zero. These entries should be read as registry fields, not as evidence that adverse events were comprehensively assessed or that no events occurred; the record does not provide denominators or further adverse-event reporting context.
Overall, the record supports a description of the design and intended measurement, not a conclusion about the observed blood pressure response. The efficacy estimates and their precision are not reported in the registry record. Any interpretation beyond the design and endpoint description would require outcome data and analysis details that are not available in this record.
9. Statistical Methods Explained
In general, randomized allocation is intended to reduce systematic differences in treatment assignment. Double masking is intended to limit the influence of knowledge about assigned conditions on participants or study personnel. These design labels do not show whether masking was successful or explain how assignments were generated and concealed. Those procedures are not reported in the registry record.
What does a crossover design imply?
In general, a crossover design allows comparisons across conditions within the same participant. Such comparisons can account for stable participant characteristics, but the method also requires attention to treatment order, changes over time, and possible carryover from an earlier condition. The record identifies a crossover model but does not report the treatment sequence, the duration or timing of each period, or a washout interval. It also does not describe whether the analysis accounted for sequence, period, or within-participant correlation. These details are necessary to evaluate the implementation and analysis of a crossover trial.
What does the endpoint summary describe?
The primary measure is continuous aortic blood pressure, expressed in mmHg, with mean and standard deviation specified as the summary statistics. In general, a mean describes the central value of a set of measurements, while a standard deviation describes their spread around that mean. The registry’s endpoint description refers to change from rest to 30 minutes after acute caffeine ingestion at Baseline and Day 7, after a 7-day period of 6g/day of Citrulline or 6 g/day of Placebo. It does not provide the component measurements or the resulting changes.
For a treatment comparison, an analysis could define a contrast between conditions or compare the change across periods. The exact contrast matters: a comparison of post-ingestion values is not necessarily the same as a comparison of rest-to-post-ingestion changes, and a comparison across Day 7 conditions is not the same as comparing Day 7 with Baseline. The record flags multiple categories or time points and does not reduce the primary outcome to one comparison. It does not report which contrast was designated for inferential testing.
How should uncertainty be understood?
In general, a confidence interval gives a range of values compatible with the data and an estimation procedure, under its assumptions. Its width reflects precision as well as sample variability. A p-value summarizes how unusual data would be under a specified null hypothesis and statistical model. Neither statistic replaces the estimated effect, and neither establishes clinical importance. The primary endpoint record contains no numerical estimate, confidence interval, or p-value to interpret.
The sample-size planning assumptions in the record describe an illustration computed from the observed effect, not the trial’s own design. Those assumptions specify 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. The record does not report the trial’s own sample-size justification. Planning illustrations are not observed power and do not establish that the trial was adequately or inadequately sized for its objective.
Why do analysis details matter?
In general, repeated measurements from the same participant are correlated rather than independent. Analyses of crossover data should reflect that structure. A model that treats measurements as independent may misrepresent uncertainty. The appropriate method depends on the design and data, and those details cannot be recovered from the crossover label alone. The statistical model, assumptions, covariate adjustment, and treatment of repeated measures are not reported in the registry record.
Multiplicity arises when several outcomes, time points, or comparisons are examined. In general, testing many contrasts can increase the chance of a seemingly notable result under a null hypothesis. The record identifies several primary-outcome categories or time points but does not report a multiplicity adjustment or a hierarchy of tests. The analysis plan and any interim analyses are not reported in the registry record. It is therefore not possible to determine how testing across the endpoint’s time points or other outcomes was handled.
The registry record lists the primary endpoint’s summary format but no numerical results or analysis estimates. It also does not report how missing measurements were handled, which participants were included in each analysis, or whether the reported analyses followed the randomized assignments. Those omissions prevent an independent assessment of the reported statistical methods or their sensitivity to alternative assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is flagged as having several categories or time points and not being reduced to one comparison. The registry record does not identify a single primary contrast for interpretation, describe a hierarchy among time points, or report a multiplicity procedure. When several comparisons are considered, general statistical practice recognizes that the chance of a false-positive finding can change; whether and how that concern was addressed in this trial is not reported in the registry record.
Missing-data handling is also not described. The record does not report the amount or pattern of missing endpoint measurements, reasons for missingness, imputation methods, or sensitivity analyses. In general, missingness can affect estimates when the availability of an observation is related to the outcome or treatment, and the implications depend on the underlying pattern and assumptions. No specific missing-data assumption can be attributed to this trial.
The registry does not report the analysis population, such as whether analyses included all randomized participants or a subset with complete measurements. It also does not state how exclusions, protocol deviations, or withdrawals were handled. The enrollment listing is not a substitute for the number contributing to a particular analysis.
Although the record gives planning assumptions for an illustrative sample-size calculation, it does not report the trial’s own statistical plan, multiplicity strategy, or interim analyses. Consequently, neither the control of testing across outcomes nor the treatment of incomplete data can be assessed from the registry record.
11. What the Result Does, and Does Not, Mean
The registry establishes that the study was designed to examine aortic blood pressure around an acute caffeine ingestion, in the context of a 7-day L-citrulline or placebo period. It also identifies the population description, interventions, crossover design, and measurement timing. These details explain the research question but do not reveal the observed response.
The record does not provide a numerical primary endpoint estimate or a selected contrast. It therefore does not show the direction or magnitude of a change, or how precisely any effect was estimated. The missing estimate also means readers cannot judge whether a result is compatible with a small effect, a larger effect, or no meaningful difference. No conclusion that caffeine, L-citrulline, or placebo did or did not alter blood pressure follows from the design description alone.
In general, statistical evidence about a treatment comparison depends on both the estimated effect and its uncertainty, together with the analysis assumptions and study design. A statement about statistical significance alone would not answer questions about effect size or clinical relevance. Here, the registry record does not include the relevant numerical inferential results, so those distinctions cannot be made for this trial.
The listed zero adverse-event fields are limited registry entries. The record does not give denominators or enough context to determine the completeness of adverse-event collection. Those entries cannot support a broad safety conclusion.
The most defensible reading is descriptive: this is a completed randomized, double-blind crossover study with an endpoint intended to capture acute aortic blood pressure response before and after a 7-day supplementation period. The registry record does not report the primary outcome result or enough analysis detail to establish what the data mean for the stated comparison.
12. Why This Trial Matters Statistically
This trial is statistically interesting because its question combines acute measurements with a supplementation period. The endpoint description involves a rest-to-post-caffeine change assessed at Baseline and Day 7, alongside L-citrulline or placebo. That structure makes it important to distinguish the acute response from changes across the longer supplementation period. The registry does not identify a single contrast that resolves those distinctions.
The crossover design also makes within-participant structure relevant. In general, such designs can use comparisons within participants, but inference depends on period order, possible carryover, and appropriate handling of repeated observations. The registry provides the design label but not the details needed to evaluate these issues or the analysis model used.
The trial highlights why an endpoint definition is not the same as a result. A precise description of the measure, units, timing, and summary statistic helps clarify what was intended to be measured. Without numerical estimates and uncertainty, however, it cannot establish the size or precision of a treatment contrast. The registry explicitly notes multiple categories or time points without reducing the primary outcome to one comparison, reinforcing the importance of a clearly specified estimand.
Finally, planning assumptions should be distinguished from evidence observed in the trial. The record describes an illustrative calculation based on the observed effect, but labels it as separate from the trial’s own design. Such planning information cannot substitute for outcome estimates or be interpreted as observed power. Together, these features make the record a useful example of why trial design, endpoint definition, analysis specification, and reported results must be read as distinct components of statistical interpretation.
13. 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.
A central limitation of the available record is that it does not report numerical primary endpoint results. There is no estimate of the aortic blood pressure response, no confidence interval, and no p-value. The primary outcome is described as spanning several categories or time points and is not reduced to a single comparison, so the target contrast is also unclear.
The record does not provide the detailed crossover schedule, treatment sequence, period lengths, or washout interval. It does not describe how repeated observations were modeled, whether period or sequence effects were considered, or what analysis population was used. These omissions make it difficult to assess whether the analysis reflected the trial design.
Participant-level descriptive information and endpoint-specific analyzed counts are not reported. The registry lists an enrollment of 16, but does not indicate how many measurements were available for each outcome or how missing values were handled. Eligibility criteria and baseline characteristics beyond the stated population description are not reported in the registry record.
The record lists Hypertension and Healthy as conditions, while the primary endpoint population is described as young, apparently healthy individuals and the title specifies males. Further detail about the enrolled participants is not reported, limiting assessment of how closely the analyzed group matched that description.
Lastly, the adverse-event fields lack denominators and additional reporting context, and the statistical plan, multiplicity handling, and interim analyses are not reported in the registry record. These limitations concern what can be concluded from the registry; they do not establish that the underlying trial lacked procedures or analyses that are simply not described there.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males — NCT02214290.
- Registry record last updated 2020-12-29; status last verified 2020-10.
- Results first posted 2020-12-29.
- 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.
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17. Record Summary
NCT02214290 is listed as a completed randomized, double-blind crossover trial sponsored by Florida State University. The title concerns oral caffeine and L-citrulline supplementation and arterial function in healthy males. The registry lists an enrollment of 16, a study start of 2012-09, and primary completion in 2014-03.
The primary endpoint is aortic blood pressure in mmHg, summarized as a mean with standard deviation. It concerns rest-to-30-minute post-caffeine changes at Baseline and Day 7, in the context of 7 days of 6g/day of Citrulline or 6 g/day of Placebo. The record identifies the endpoint but flags multiple categories or time points without reducing them to one comparison.
Numerical primary results, an analysis contrast, missing-data methods, and detailed statistical methods are not reported in the registry record. The design and measurement question can be described, but the endpoint’s estimated effect and precision cannot be interpreted from this record.