Elderly, Healthy
Conditions
Brief summary
This study will measure the oral bioavailability and pharmacokinetics of known bioactive compounds from a standardized Centella asiatica water extract (CAW) product (CAP) in cognitively healthy elders.
Detailed description
PRIMARY OBJECTIVES: 1. To assess the bioavailability and rate of clearance of Centella asiatica derived compounds in the plasma and urine of cognitively healthy elders over 12 hours. 2. To determine the acute tolerability of a Centella asiatica product in cognitively healthy elders. OUTLINE: Participants will orally consume a single administration of a standardized Centella asiatica water extract product (CAP). Two doses (2g and 4g CAW) will be administered on separate occasions, at least two weeks apart. The levels of known bioactive compounds present in Centella asiatica will be measured in human plasma and urine over 12 hours after administration of each of the doses.
Interventions
2g Centella asiatica water extract product is a powder containing Centella asiatica water extract (CAW) and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
4g Centella asiatica water extract product is a powder containing Centella asiatica water extract (CAW) and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomization will use an arm equivalence design to promote equal numbers of participants for each order schema.
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 65-85, male and female 2. Sufficient English language skills to complete all tests 3. Sufficient vision and hearing to complete all tests 4. No known allergies to Centella asiatica or CAP components 5. Willingness to discontinue all botanical dietary supplements for one week prior to and during each study visit 6. Willingness to comply with a 48-hour low plant diet for each study visit 7. Absence of significant depression symptoms (Geriatric Depression Scale-15 score of \<12) 8. Body Mass Index (BMI) greater than 17 and less than 35 at screening 9. Non-demented, defined as Clinical Dementia Rating (CDR) score of zero and Mini Mental State Examination (MMSE) score \>28 10. General health status that will not interfere with the ability to complete the study
Exclusion criteria
1. Current smoking, alcohol or substance abuse according to DSM-V criteria 2. Women who are pregnant, planning to become pregnant or breastfeeding 3. Men who are actively trying to conceive a child or planning to within three months of study completion 4. Severe aversion to venipuncture 5. Abnormal laboratory evaluation indicating asymptomatic and untreated urinary tract infection 6. Cancer within the last five years, with the exception of localized prostate cancer (Gleason Grade \<3) and non-metastatic skin cancers 7. Comorbid conditions such as diabetes mellitus, kidney failure, liver failure, hepatitis, blood disorders, clinical symptomatic orthostatic hypotension, and unstable or significantly symptomatic cardiovascular disease 8. Significant disease of the central nervous system such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke 9. Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-V criteria 10. Medications: sedatives (except those used occasionally for sleep), central nervous system active medications that have not been stable for two months (including beta blockers, cimetidine, SSRIs, SNRIs), anticoagulants (i.e. Warfarin), investigational drugs used within five half-lives of baseline visit, systemic corticosteroids, neuroleptics, anti-Parkinsonian agents, narcotic analgesics, nicotine (tobacco, patches, gum, lozenges, etc.), Cannabis sativa (herb or edibles) 11. Diseases associated with dementia such as Alzheimer's disease, vascular dementia, normal pressure hydrocephalus or Parkinson's disease with a CDR score \>0.5 and MMSE score \<28 12. Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes). | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 12 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration and area under the curve) for each of the two doses (2g and 4g). |
| Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes). | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 12 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration and area under the curve) for each of the two doses (2g and 4g). |
| Half-life | A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes). | The half-life (t1/2) of the known bioactive compounds was calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals. |
| Time of Maximum Concentration | A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes). | The time of maximum concentration (tmax) of the known bioactive compounds and their metabolites will be calculated from the concentrations measured by high performance liquid chromatography tandem mass spectrometry in order to help determine dosage intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index | 720 minutes after administration | Height in centimeters and weight in kilograms will be measured and aggregated to measure body mass index in kilograms per meter squared (kg/m2). |
| Urinary Excretion | Over 12 hours post-administration | The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in a pooled urine sample collected over 12 hours after CAP administration and analyzed using high performance liquid chromatography tandem mass spectrometry. |
| Seated Diastolic Blood Pressure | 720 minutes after administration | Seated blood pressure will be measured in millimeters mercury. |
| Participants With Change in Electrocardiography | 0, 360 and 720 minutes after administration | Resting electrocardiography will be measured for up to five minutes using a five lead mobile electrocardiogram. The investigators will determine the number of participants who develop changes in electrocardiography compared to the zero minute timepoint following CAP administration. |
| Oral Temperature | 720 minutes after administration | Oral temperature will be measured in degrees Fahrenheit by means of a thermometer. |
| Pulse Rate | 720 minutes after administration | Pulse rate will be measured peripherally over one minute. |
| Seated Systolic Blood Pressure | 720 minutes after administration | Seated blood pressure will be measured in millimeters mercury. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants including those in the (a) 2g CAW, then 4g CAW arm or (b) 4g CAW then 2g CAW arm | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Blood draws could not be successfully obtained | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 5.5 |
| Alanine aminotransferase | 30.1 U/L STANDARD_DEVIATION 2.5 |
| Albumin | 4.0 g/dL STANDARD_DEVIATION 0.1 |
| Anion gap | 5.3 mEq/L STANDARD_DEVIATION 0.5 |
| Aspartate aminotransferase | 24.6 U/L STANDARD_DEVIATION 0.7 |
| Blood glucose | 90.6 mg/dL STANDARD_DEVIATION 4.3 |
| Blood urea nitrogen | 15.8 mg/dL STANDARD_DEVIATION 1 |
| Body mass index | 28.5 kg/m^2 STANDARD_DEVIATION 1.5 |
| Body temperature | 98.3 degrees Fahrenheit STANDARD_DEVIATION 0.2 |
| Calcium | 9.2 mg/dL STANDARD_DEVIATION 0.1 |
| Chloride | 106.5 mmol/L STANDARD_DEVIATION 0.5 |
| Creatinine | 0.7 mg/dL STANDARD_DEVIATION 0.6 |
| Diastolic blood pressure | 78 mmHg STANDARD_DEVIATION 2 |
| Heart rate | 67 beats per minute STANDARD_DEVIATION 4 |
| Hematocrit | 46.4 percentage STANDARD_DEVIATION 1.4 |
| Hemoglobin | 15.3 g/dL STANDARD_DEVIATION 0.5 |
| Platelet | 233.9 10^3 cells/cu mm STANDARD_DEVIATION 7.5 |
| Potassium | 4.0 mmol/L STANDARD_DEVIATION 0.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Red blood cell | 5.0 10^6 cells/cu mm STANDARD_DEVIATION 0.2 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
| Sodium | 140.5 mmol/L STANDARD_DEVIATION 0.5 |
| Systolic blood pressure | 125 mmHg STANDARD_DEVIATION 4 |
| total bilirubin | 0.5 mg/dL STANDARD_DEVIATION 0.03 |
| Total CO2 | 28.9 mmol/L STANDARD_DEVIATION 0.5 |
| Total protein | 7.4 g/dL STANDARD_DEVIATION 0.1 |
| White blood cell | 6.7 10^3 cells/cu mm STANDARD_DEVIATION 0.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Half-life
The half-life (t1/2) of the known bioactive compounds was calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals.
Time frame: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2g CAW Dose | Half-life | Ferulic acid | 14.1 hours | Standard Error 3.9 |
| 2g CAW Dose | Half-life | Asiatic acid | 4.1 hours | Standard Error 0.7 |
| 2g CAW Dose | Half-life | 3-(3-hydroxyphenyl)propionic acid | 5 hours | Standard Error 2 |
| 2g CAW Dose | Half-life | Dihydroferulic acid | 7.1 hours | Standard Error 1.7 |
| 2g CAW Dose | Half-life | Isoferulic acid | 7 hours | Standard Error 2.4 |
| 2g CAW Dose | Half-life | Caffeic acid | 8.4 hours | Standard Error 3 |
| 2g CAW Dose | Half-life | Madecassic acid | 9.2 hours | Standard Error 3.7 |
| 2g CAW Dose | Half-life | Dicaffeoylquinic acids | 2 hours | Standard Error 1.2 |
| 2g CAW Dose | Half-life | Monocaffeoylquinic acids | 3.4 hours | Standard Error 1.1 |
| 2g CAW Dose | Half-life | Dihydrocaffeic acid | 1.8 hours | Standard Error 1.2 |
| 4g CAW Dose | Half-life | Monocaffeoylquinic acids | 1.7 hours | Standard Error 1.1 |
| 4g CAW Dose | Half-life | Asiatic acid | 4.9 hours | Standard Error 1.3 |
| 4g CAW Dose | Half-life | Dihydrocaffeic acid | 1.9 hours | Standard Error 0.8 |
| 4g CAW Dose | Half-life | Dihydroferulic acid | 6.6 hours | Standard Error 3.8 |
| 4g CAW Dose | Half-life | Dicaffeoylquinic acids | 2.6 hours | Standard Error 1.8 |
| 4g CAW Dose | Half-life | Ferulic acid | 2.9 hours | Standard Error 1.3 |
| 4g CAW Dose | Half-life | 3-(3-hydroxyphenyl)propionic acid | 2.6 hours | Standard Error 0.5 |
| 4g CAW Dose | Half-life | Isoferulic acid | 3.5 hours | Standard Error 0.5 |
| 4g CAW Dose | Half-life | Madecassic acid | 6.7 hours | Standard Error 0.8 |
| 4g CAW Dose | Half-life | Caffeic acid | 10.3 hours | Standard Error 3.7 |
Primary
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica.
Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 12 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration and area under the curve) for each of the two doses (2g and 4g).
Time frame: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Asiatic acid | 174 ng/mL | Standard Error 22 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Caffeic acid | 0.3 ng/mL | Standard Error 0.1 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dihydrocaffeic acid | 0.4 ng/mL | Standard Error 0.1 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dihydroferulic acid | 9.3 ng/mL | Standard Error 4.4 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dicaffeoylquinic acids | 1.2 ng/mL | Standard Error 0.6 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Ferulic acid | 1.5 ng/mL | Standard Error 0.3 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | 3-(3-hydroxyphenyl)propionic acid | 5.8 ng/mL | Standard Error 3 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Isoferulic acid | 1.5 ng/mL | Standard Error 0.8 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Madecassic acid | 107 ng/mL | Standard Error 18 |
| 2g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Monocaffeoylquinic acids | 1.6 ng/mL | Standard Error 0.5 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Isoferulic acid | 1.5 ng/mL | Standard Error 0.4 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Asiatic acid | 372 ng/mL | Standard Error 53 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Ferulic acid | 1.5 ng/mL | Standard Error 0.6 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Caffeic acid | 0.5 ng/mL | Standard Error 0.1 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Monocaffeoylquinic acids | 4.2 ng/mL | Standard Error 1.4 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dihydrocaffeic acid | 0.5 ng/mL | Standard Error 0.1 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | 3-(3-hydroxyphenyl)propionic acid | 10.6 ng/mL | Standard Error 2.9 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dihydroferulic acid | 8.1 ng/mL | Standard Error 2.9 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Madecassic acid | 197 ng/mL | Standard Error 43 |
| 4g CAW Dose | Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. | Dicaffeoylquinic acids | 1.9 ng/mL | Standard Error 0.8 |
Primary
Time of Maximum Concentration
The time of maximum concentration (tmax) of the known bioactive compounds and their metabolites will be calculated from the concentrations measured by high performance liquid chromatography tandem mass spectrometry in order to help determine dosage intervals
Time frame: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2g CAW Dose | Time of Maximum Concentration | Asiatic acid | 2.2 hours | Standard Error 0.4 |
| 2g CAW Dose | Time of Maximum Concentration | Caffeic acid | 5.3 hours | Standard Error 1.9 |
| 2g CAW Dose | Time of Maximum Concentration | Dihydrocaffeic acid | 6.1 hours | Standard Error 1.7 |
| 2g CAW Dose | Time of Maximum Concentration | Dihydroferulic acid | 5.9 hours | Standard Error 1.6 |
| 2g CAW Dose | Time of Maximum Concentration | Dicaffeoylquinic acids | 3.7 hours | Standard Error 1.9 |
| 2g CAW Dose | Time of Maximum Concentration | Ferulic acid | 5.9 hours | Standard Error 1.3 |
| 2g CAW Dose | Time of Maximum Concentration | 3-(3-hydroxyphenyl)propionic acid | 7.4 hours | Standard Error 1.5 |
| 2g CAW Dose | Time of Maximum Concentration | Isoferulic acid | 2.4 hours | Standard Error 1 |
| 2g CAW Dose | Time of Maximum Concentration | Madecassic acid | 2.4 hours | Standard Error 0.3 |
| 2g CAW Dose | Time of Maximum Concentration | Monocaffeoylquinic acids | 1.2 hours | Standard Error 0.4 |
| 4g CAW Dose | Time of Maximum Concentration | Isoferulic acid | 1 hours | Standard Error 0.32 |
| 4g CAW Dose | Time of Maximum Concentration | Asiatic acid | 2.8 hours | Standard Error 0.2 |
| 4g CAW Dose | Time of Maximum Concentration | Ferulic acid | 7.1 hours | Standard Error 1.2 |
| 4g CAW Dose | Time of Maximum Concentration | Caffeic acid | 4.5 hours | Standard Error 1.6 |
| 4g CAW Dose | Time of Maximum Concentration | Monocaffeoylquinic acids | 3.4 hours | Standard Error 1.2 |
| 4g CAW Dose | Time of Maximum Concentration | Dihydrocaffeic acid | 3.2 hours | Standard Error 1.3 |
| 4g CAW Dose | Time of Maximum Concentration | 3-(3-hydroxyphenyl)propionic acid | 5.7 hours | Standard Error 0.7 |
| 4g CAW Dose | Time of Maximum Concentration | Dihydroferulic acid | 5.7 hours | Standard Error 1.5 |
| 4g CAW Dose | Time of Maximum Concentration | Madecassic acid | 2.7 hours | Standard Error 0.2 |
| 4g CAW Dose | Time of Maximum Concentration | Dicaffeoylquinic acids | 4.3 hours | Standard Error 1.7 |
Primary
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product.
Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 12 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration and area under the curve) for each of the two doses (2g and 4g).
Time frame: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Asiatic acid | 48755 ng/mL*hr | Standard Error 7152 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Caffeic acid | 1.8 ng/mL*hr | Standard Error 0.5 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dihydrocaffeic acid | 1.7 ng/mL*hr | Standard Error 0.6 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dihydroferulic acid | 35.6 ng/mL*hr | Standard Error 18.6 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dicaffeoylquinic acids | 3.4 ng/mL*hr | Standard Error 1.8 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Ferulic acid | 11.3 ng/mL*hr | Standard Error 2.9 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | 3-(3-hydroxyphenyl)propionic acid | 56.8 ng/mL*hr | Standard Error 31.7 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Isoferulic acid | 5.3 ng/mL*hr | Standard Error 1.6 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Madecassic acid | 26771 ng/mL*hr | Standard Error 3585 |
| 2g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Monocaffeoylquinic acids | 6.2 ng/mL*hr | Standard Error 2.4 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Isoferulic acid | 7.4 ng/mL*hr | Standard Error 1.6 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Asiatic acid | 91330 ng/mL*hr | Standard Error 17723 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Ferulic acid | 9.9 ng/mL*hr | Standard Error 2.8 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Caffeic acid | 2.4 ng/mL*hr | Standard Error 0.6 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Monocaffeoylquinic acids | 10.1 ng/mL*hr | Standard Error 3.9 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dihydrocaffeic acid | 1.9 ng/mL*hr | Standard Error 0.5 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | 3-(3-hydroxyphenyl)propionic acid | 50.2 ng/mL*hr | Standard Error 15.1 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dihydroferulic acid | 41.0 ng/mL*hr | Standard Error 12.7 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Madecassic acid | 48373 ng/mL*hr | Standard Error 12476 |
| 4g CAW Dose | Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. | Dicaffeoylquinic acids | 5.0 ng/mL*hr | Standard Error 1.5 |
Secondary
Body Mass Index
Height in centimeters and weight in kilograms will be measured and aggregated to measure body mass index in kilograms per meter squared (kg/m2).
Time frame: 720 minutes after administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2g CAW Dose | Body Mass Index | 28.4 kg/m^2 | Standard Error 1.3 |
| 4g CAW Dose | Body Mass Index | 28 kg/m^2 | Standard Error 1.4 |
Secondary
Oral Temperature
Oral temperature will be measured in degrees Fahrenheit by means of a thermometer.
Time frame: 720 minutes after administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2g CAW Dose | Oral Temperature | 98.2 degrees Fahrenheit | Standard Error 0.1 |
| 4g CAW Dose | Oral Temperature | 98.1 degrees Fahrenheit | Standard Error 0.1 |
Secondary
Participants With Change in Electrocardiography
Resting electrocardiography will be measured for up to five minutes using a five lead mobile electrocardiogram. The investigators will determine the number of participants who develop changes in electrocardiography compared to the zero minute timepoint following CAP administration.
Time frame: 0, 360 and 720 minutes after administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2g CAW Dose | Participants With Change in Electrocardiography | 0 Participants |
| 4g CAW Dose | Participants With Change in Electrocardiography | 0 Participants |
Secondary
Pulse Rate
Pulse rate will be measured peripherally over one minute.
Time frame: 720 minutes after administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2g CAW Dose | Pulse Rate | 69 beats per minute | Standard Error 4 |
| 4g CAW Dose | Pulse Rate | 64 beats per minute | Standard Error 3 |
Secondary
Seated Diastolic Blood Pressure
Seated blood pressure will be measured in millimeters mercury.
Time frame: 720 minutes after administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2g CAW Dose | Seated Diastolic Blood Pressure | 74 mmHg | Standard Error 3 |
| 4g CAW Dose | Seated Diastolic Blood Pressure | 69 mmHg | Standard Error 1 |
Secondary
Seated Systolic Blood Pressure
Seated blood pressure will be measured in millimeters mercury.
Time frame: 720 minutes after administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2g CAW Dose | Seated Systolic Blood Pressure | 125 mmHg | Standard Error 4 |
| 4g CAW Dose | Seated Systolic Blood Pressure | 119 mmHg | Standard Error 5 |
Secondary
Urinary Excretion
The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in a pooled urine sample collected over 12 hours after CAP administration and analyzed using high performance liquid chromatography tandem mass spectrometry.
Time frame: Over 12 hours post-administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2g CAW Dose | Urinary Excretion | Asiatic acid | 0 micrograms | Standard Error 0 |
| 2g CAW Dose | Urinary Excretion | Asiaticoside | 20.7 micrograms | Standard Error 6.7 |
| 2g CAW Dose | Urinary Excretion | Caffeic acid | 42.8 micrograms | Standard Error 11.6 |
| 2g CAW Dose | Urinary Excretion | Dihydrocaffeic acid | 26.8 micrograms | Standard Error 10 |
| 2g CAW Dose | Urinary Excretion | Dihydroferulic acid | 225.5 micrograms | Standard Error 83.5 |
| 2g CAW Dose | Urinary Excretion | Dicaffeoylquinic acids | 0 micrograms | Standard Error 0 |
| 2g CAW Dose | Urinary Excretion | Ferulic acid | 146.8 micrograms | Standard Error 33.5 |
| 2g CAW Dose | Urinary Excretion | 3-(3-hydroxyphenyl)propionic acid | 223.4 micrograms | Standard Error 76.7 |
| 2g CAW Dose | Urinary Excretion | Isoferulic acid | 65.9 micrograms | Standard Error 23.1 |
| 2g CAW Dose | Urinary Excretion | Madecassic acid | 0 micrograms | Standard Error 0 |
| 2g CAW Dose | Urinary Excretion | Madecassoside | 0 micrograms | Standard Error 0 |
| 2g CAW Dose | Urinary Excretion | Monocaffeoylquinic acids | 21.3 micrograms | Standard Error 8.6 |
| 4g CAW Dose | Urinary Excretion | Madecassoside | 0 micrograms | Standard Error 0 |
| 4g CAW Dose | Urinary Excretion | Asiatic acid | 0 micrograms | Standard Error 0 |
| 4g CAW Dose | Urinary Excretion | Ferulic acid | 137.4 micrograms | Standard Error 24.6 |
| 4g CAW Dose | Urinary Excretion | Asiaticoside | 18.6 micrograms | Standard Error 4.5 |
| 4g CAW Dose | Urinary Excretion | Madecassic acid | 0 micrograms | Standard Error 0 |
| 4g CAW Dose | Urinary Excretion | Caffeic acid | 48.7 micrograms | Standard Error 9.3 |
| 4g CAW Dose | Urinary Excretion | 3-(3-hydroxyphenyl)propionic acid | 247.9 micrograms | Standard Error 73.6 |
| 4g CAW Dose | Urinary Excretion | Dihydrocaffeic acid | 24.8 micrograms | Standard Error 6.1 |
| 4g CAW Dose | Urinary Excretion | Monocaffeoylquinic acids | 19.3 micrograms | Standard Error 2.6 |
| 4g CAW Dose | Urinary Excretion | Dihydroferulic acid | 225.1 micrograms | Standard Error 94.8 |
| 4g CAW Dose | Urinary Excretion | Isoferulic acid | 225.1 micrograms | Standard Error 15.9 |
| 4g CAW Dose | Urinary Excretion | Dicaffeoylquinic acids | 0 micrograms | Standard Error 0 |