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 Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment (NCT03937908), a randomized early/phase 1 study. The primary outcome is Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03937908 |
| Phase | EARLY/Phase 1 |
| Condition | Cognitive Impairment, Elderly |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oregon Health and Science University |
| Results posted | Yes |
2. Clinical Question
Population
Elderly participants with mild cognitive impairment who were receiving cholinesterase inhibitor therapy. The registry record reports enrollment of 5, but the posted primary results do not provide concentration estimates or participant-level results.
Intervention
A single oral administration of 2g of standardized Centella asiatica water extract product, dissolved in 10-12 ounce of water and taken on an empty stomach, or a single oral administration of 4g prepared and taken in the same way.
Comparator
The 2g and 4g doses were the active dose conditions in a randomized crossover design. The record does not describe a placebo or untreated condition. It does not report the treatment sequence or the interval between administrations.
Primary question
How do plasma concentrations of Centella asiatica-derived bioactive compounds vary after each dose, including the maximum concentration reached during the measured period? The registry describes Cmax as the primary measure and states that concentrations were measured over a 10-hour post-administration period. Although the study aimed to characterize pharmacokinetics, the primary outcome values are not reported in the registry record.
3. Trial Design
This was a randomized, double-masked, crossover study listed as early phase 1. Its stated focus was pharmacokinetics rather than a clinical efficacy comparison. Participants were elderly people with mild cognitive impairment receiving cholinesterase inhibitor therapy. The registry reports enrollment of 5 and lists 2g and 4g single-dose conditions of a standardized Centella asiatica water extract product.
In a crossover design, participants receive more than one study condition, so comparisons can potentially use measurements from the same participant under each condition. That feature can be useful in pharmacokinetic research, where concentration profiles are measured repeatedly. However, the registry record does not describe the dose sequence, the interval between administrations, or whether any washout was used. It also does not describe the precise randomization procedure or how masking was maintained.
Each dose was dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. The planned concentration measurements covered 10 hours after administration, at 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes. The study began on 2019-10-31, had a primary completion date of 2020-12-21, and is listed as terminated. The reason for termination is not reported in the registry record.
The design and small enrollment describe an exploratory pharmacokinetic study. They do not establish that the study was designed to test clinical benefit or to compare changes in cognitive status. The registry record does not report a sample-size justification or a detailed statistical analysis plan.
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 | Experimental: 2g CAP Then 4g CAP | Experimental: 4g CAP Then 2g CAP |
|---|---|---|
| STARTED | 2 | 3 |
| COMPLETED | 2 | 2 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Experimental: 2g CAP Then 4g CAP | Experimental: 4g CAP Then 2g CAP |
|---|---|---|
| Study discontinuation due to pandemic restrictions | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic parameter (Cmax) and time curves was calculated using non-compartmental analysis of plasma concentration versus time data using Excel software PK-solver (version 2.0).
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 | All Participants |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 5 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 5 |
| Body mass index | kg/m^2 | 28 (SD 2) |
| White blood cells | x10^3 cells/uL | 7.28 (SD 0.60) |
| Systolic blood pressure | mmHg | 132 (SD 7) |
| Diastolic blood pressure | mmHg | 81 (SD 3) |
| Body temperature | Celsius | 36.7 (SD 0.1) |
| Heart rate | beats per minute | 68 (SD 5) |
| Red blood cells | x10^6 cells/uL | 4.64 (SD 0.21) |
| Hemoglobin | g/dL | 14.3 (SD 0.6) |
| Hematocrit | percentage | 44 (SD 2) |
| Platelets | x10^3 platelets/uL | 259 (SD 20) |
6. Primary Endpoint
The registry lists the primary outcome as Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax), measured over A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes)..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was peak plasma concentration, Cmax, for Centella asiatica-derived bioactive compounds after oral administration of the product. The registry description includes triterpenes, caffeoylquinic acids, and their metabolites. Plasma concentration was to be measured from blood samples collected during the 10-hour post-administration period using high performance liquid chromatography tandem mass spectrometry. Cmax is the maximum concentration observed on a concentration-versus-time profile.
Pharmacokinetic studies use Cmax to describe the peak level reached after a dose. It can be considered alongside other features of the concentration curve, such as the timing of the peak and the area under the curve, because these describe different aspects of exposure. The registry's study summary also identifies AUC0-12, clearance, and tmax as intended pharmacokinetic quantities, while the listed primary outcome is Cmax. The record does not provide numeric Cmax estimates for either dose.
The registry says Cmax and time curves were calculated using non-compartmental analysis of plasma concentration versus time data with Excel software PK-solver (version 2.0). It describes the reported measure as a mean with standard error. These details identify the intended summary and analysis approach, but without posted values they do not indicate the size or precision of the observed peak concentrations.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the objective and planned measurement of plasma concentrations, but it does not report numeric results for the primary endpoint. Therefore, the posted record cannot establish the mean Cmax for either dose, the uncertainty around those estimates, or how the concentration profiles differed between dose conditions. It also does not report a statistical comparison of the primary endpoint. No conclusion about the direction or magnitude of a dose-related difference can be drawn from the outcome information in the record.
The study's crossover structure is relevant to interpretation because dose conditions may be compared within the same participant. Such a design can account for stable differences between participants when the analysis appropriately preserves the within-person pairing. The registry record does not state how the dose sequence, period effects, or within-participant correlation were handled. Without that information and the reported outcome data, no adjusted or paired estimate can be reconstructed.
The planned concentration profile included multiple collection times, and the primary outcome description concerns multiple compounds and their metabolites. A peak concentration is derived from the measured profile; it is not itself a complete description of exposure. The registry summary also mentions AUC0-12, clearance, and tmax, and lists secondary outcomes for area under the curve, total urinary excretion, and NRF2 expression. Numeric findings for these measures are not reported in the registry record.
Enrollment was 5, while the adverse-event record gives an at-risk count of 4 for each dose condition. These figures describe different parts of the registry and should not be treated as interchangeable. The record does not explain the relationship between enrollment and the safety denominators. In a crossover study, participants may contribute information under more than one condition, so the at-risk counts should not be added to infer a participant total.
The study is listed as terminated, but the reason and its consequences for completion of planned measurements are not reported in the registry record. The available information supports describing the study's design, intended pharmacokinetic measures, and posted safety counts. It does not support an efficacy claim or a quantitative conclusion about the pharmacokinetic results.
9. Statistical Methods Explained
The registry describes a continuous primary measure summarized as a mean with standard error. A mean represents the average of measured values. The standard error describes the precision of an estimated mean, rather than the spread of individual measurements. It is useful for understanding how precisely a mean has been estimated, but it does not by itself show the range of participant-level values. No primary endpoint means or standard errors are reported in the registry record.
What does Cmax represent?
Cmax is the peak concentration identified from a concentration-versus-time profile. Here, plasma samples were planned at 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes after administration. The registry describes deriving pharmacokinetic parameters from those profiles using non-compartmental analysis. In general, non-compartmental methods summarize observed concentration data without requiring the analyst to specify a compartment model for the body's handling of a compound. The registry does not provide the calculations or estimates needed to assess the resulting Cmax values.
How should uncertainty be read?
In general, a confidence interval expresses a range of values compatible with the data and the assumptions of the analysis, and can help convey the precision of an estimate. A standard error is another summary of uncertainty in an estimated mean, but it is not a confidence interval. The registry lists standard error as the dispersion measure for the primary outcome; it does not report a confidence interval or numerical standard error. Consequently, the precision of the primary endpoint estimates cannot be evaluated from the posted record.
What does crossover imply for analysis?
In general, a crossover comparison can take account of the fact that repeated measurements from the same participant are related. An analysis that treats related observations as independent may not represent the design accurately. Period or sequence effects may also matter when participants receive conditions at different times. The registry identifies randomization, double masking, and a crossover model, but does not report the treatment sequence, any washout, or the statistical handling of paired observations, period effects, or sequence effects. Those details are not reported in the registry record.
What can the planning illustration tell readers?
The registry's sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is framed around detecting a stated fraction of the observed effect. It is not a report of the trial's original design justification and is not observed power. The record does not report a sample-size justification for the study itself. No planning sample-size values are included in the registry record for interpretation.
How should the record's analyses be understood?
The registry lists 6 outcome measures and 53 analyses. Those counts do not identify which outcomes were analyzed together, what comparisons were specified, or whether adjustments were made for multiple testing. The registry record does not report a complete statistical analysis plan, the treatment of missing observations, or the analysis populations. The result information also does not provide the numerical primary outcome estimates. These omissions limit independent assessment of the analysis and its precision.
The primary endpoint description says Excel software PK-solver (version 2.0) was used for non-compartmental analysis. This identifies the software and general approach recorded by the study, but does not provide enough detail to reproduce the analysis. In general, reproducibility also depends on the data included, calculation choices, handling of incomplete profiles, and definitions used for each compound. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 6 outcome measures and 53 analyses. Its primary outcome description includes multiple bioactive compounds and metabolites measured across a concentration-time profile. The secondary outcomes include area under the curve of concentration-versus-time profiles, total urinary excretion, and NRF2 expression. This creates several potential measurements and comparisons, but the registry record does not explain which were treated as confirmatory, whether a hierarchy of outcomes was used, or whether any adjustment for multiple testing was planned or applied.
Multiplicity matters because making many statistical comparisons can increase the chance that at least one result appears notable by chance. In general, approaches such as prespecifying a primary comparison or adjusting inference across a family of tests can address different aspects of that issue. The registry record does not report whether such approaches were used. The posted primary result values are not available in the record, so the number or pattern of statistically significant findings cannot be assessed.
The record does not describe missing-data handling, how many participants contributed to each concentration profile, or the analysis populations used for the primary and secondary outcomes. It also does not report whether incomplete sampling profiles were included in pharmacokinetic calculations. These details matter because concentration estimates can depend on which time points and participants contribute to an analysis. No assumptions about missingness or analysis exclusions can be inferred from the listed enrollment and safety counts.
The crossover design makes within-participant data handling especially relevant. The registry does not report how paired observations, treatment sequence, or period effects were incorporated into statistical tests or estimates. These statistical-plan details are not reported in the registry record.
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 |
|---|---|---|---|
| 2g CAP | 0 | 4 | 0.0% |
| 4g CAP | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 2g CAP | 0 of 4 |
| 4g CAP | 0 of 4 |
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 |
|---|---|
| 2g CAP | 4 of 4 |
| 4g CAP | 4 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 2g CAP | 4g CAP |
|---|---|---|---|
| Increased appetite | Gastrointestinal disorders | 1 of 4 | 2 of 4 |
| Drowsiness | Psychiatric disorders | 1 of 4 | 1 of 4 |
| Allergy symptoms | Immune system disorders | 2 of 4 | 0 of 4 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1 of 4 | 1 of 4 |
| Heart racing or irregular beating | Cardiac disorders | 1 of 4 | 1 of 4 |
| Hypertension/elevated blood pressure | Cardiac disorders | 1 of 4 | 1 of 4 |
| Increased urination | Renal and urinary disorders | 0 of 4 | 2 of 4 |
| Generalized pain | General disorders | 1 of 4 | 1 of 4 |
| Anxiety | Psychiatric disorders | 0 of 4 | 1 of 4 |
| Headache | Nervous system disorders | 0 of 4 | 1 of 4 |
The adverse-event record lists 0 serious adverse events and 0 deaths in each dose group. It also records 4 participants at risk and 4 affected by other adverse events in the 2g CAP group, and 4 at risk and 4 affected in the 4g CAP group. No serious adverse-event terms are listed.
These are registry counts, not estimates of comparative risk. The record does not provide event descriptions, severity categories for the other adverse events, timing, or an assessment of whether events were related to the study product. The absence of reported serious events in these entries does not establish that no serious events could occur in other settings.
The study is described as a crossover, and the record does not explain whether the same participants contributed safety information under both dose conditions. The at-risk counts for the groups should therefore be read separately and should not be added to infer a number of distinct participants. Enrollment is listed as 5, while the adverse-event denominators are 4 for each condition; the registry does not explain this difference.
12. What the Result Does, and Does Not, Mean
This record describes an early-phase pharmacokinetic study of 2g and 4g doses of a Centella asiatica water extract product in elderly participants with mild cognitive impairment receiving cholinesterase inhibitor therapy. It specifies an intended focus on plasma concentrations of bioactive compounds and their metabolites after single oral doses. The planned measurements and non-compartmental approach explain what the investigators sought to characterize.
The posted record does not report the primary Cmax values, standard errors, or a statistical comparison between doses. It also does not report numeric results for the secondary outcomes. As a result, readers cannot determine from this record how high concentrations reached, how variable or precise the estimates were, or whether the two dose conditions produced different profiles. No conclusion that either dose performed better or worse is warranted by the available outcome information.
The stated motivation was to use pharmacokinetic data to inform decisions about dosage and dosing frequency for future clinical trials. That is a research-development purpose, not a demonstration of clinical benefit. The registry describes measurements of plasma and urine and identifies NRF2 expression as a secondary outcome; it does not report cognitive outcomes or evidence that the product changes cognition.
The safety entries show no serious adverse events or deaths recorded for either dose condition, alongside other adverse events recorded for all participants in each condition's listed at-risk group. These counts need the design and reporting limitations in mind: the registry does not detail the events or clarify whether the same participants contributed to both conditions. They are not a complete basis for judging safety.
Overall, the record documents a small, terminated pharmacokinetic study with an explicit measurement plan, but without posted primary outcome estimates. It can inform readers about the intended research question and recorded design; it cannot support a quantitative account of the pharmacokinetic findings or a clinical efficacy claim.
13. Why This Trial Matters Statistically
This study illustrates a common role for early-phase clinical research: characterizing drug-related exposure before later trials address clinical outcomes. Measuring plasma concentrations after oral administration can describe the timing and magnitude of exposure to bioactive compounds. Cmax is one such measure, while area under the curve, clearance, and tmax represent other intended aspects of pharmacokinetics. These quantities answer questions about exposure, not whether a treatment improves a health outcome.
The randomized, double-masked crossover design is also statistically relevant. In general, comparing conditions within the same participant can reduce the influence of stable between-person differences. But that potential benefit depends on an analysis that reflects the repeated-measures structure and on adequate reporting of sequence and period details. The registry identifies the design but does not report how those features were handled in the analysis.
For readers, the distinction between a clearly specified endpoint and a reported result is important. The registry describes the primary measure, sampling schedule, assay approach, summary statistic, and non-compartmental software. Yet it does not provide the numerical endpoint estimates or their uncertainty. Methods alone cannot establish what the observed concentration profiles were.
The record also makes visible the limits of registry-based safety interpretation. It gives group-specific serious and other adverse-event counts, but not event descriptions or context for the crossover denominators. Reading these counts without treating each dose group as a separate set of unique people avoids an unsupported participant total.
Finally, a sample-size planning illustration based on an observed effect should not be confused with original trial planning or observed power. The registry's design justification and full analysis plan are not reported. Keeping these distinctions clear helps separate the study's intended purpose, its recorded methods, and the results that are actually available.
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 limitation for interpreting the study is that numeric primary endpoint results are not reported in the registry record. The record does not provide mean Cmax estimates, standard errors, or a dose comparison. Without these values, the magnitude and precision of the observed plasma concentrations cannot be assessed. Numeric findings for the listed secondary outcomes are also not reported.
Enrollment is listed as 5, but the adverse-event record lists 4 at risk in each dose condition. The registry does not explain the difference or state how many participants contributed to each pharmacokinetic analysis. Because the design is crossover, the group-specific safety entries do not establish the number of distinct participants represented across conditions.
The record does not report the reason the study was terminated or whether termination affected completion of planned sampling or analysis. It does not describe the treatment sequence, interval between administrations, washout, or handling of period and sequence effects. These omissions make it difficult to assess how the crossover design was implemented and analyzed.
Multiplicity procedures, missing-data methods, analysis populations, and the full statistical analysis plan are not reported in the registry record. The outcome description states a general non-compartmental approach and names the software, but does not supply details sufficient to reproduce the calculations. The registry also does not provide a sample-size justification for the original study. Together, these reporting gaps constrain assessment of the results beyond the design and measures described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment — NCT03937908.
- Registry record last updated 2022-05-04; status last verified 2022-04.
- Results first posted 2022-05-04.
- 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
The registry record describes a randomized, double-masked, early phase 1 crossover study of single oral doses of 2g and 4g Centella asiatica water extract product in elderly participants with mild cognitive impairment receiving cholinesterase inhibitor therapy. Enrollment is listed as 5; the study is listed as terminated.
The primary outcome was mean peak plasma concentration of Centella asiatica bioactive compounds, measured over a 10-hour post-administration period and analyzed using non-compartmental methods. The record does not report numeric primary outcome results or their standard errors. Secondary outcomes included area under the curve, total urinary excretion, and NRF2 expression.
The adverse-event record lists 0 serious adverse events and 0 deaths for each dose group. Other adverse events were recorded for 4 participants at risk in each group. The registry does not provide event details, explain the safety denominators, or report the reason for termination.