Pharmacokinetics of Centella Asiatica in the Elderly

Early Phase 1

Completed

• Conditions: Healthy; Elderly
• Interventions: Drug: 2g Centella asiatica water extract product; Drug: 4g Centella asiatica water extract product

• Registration Number: NCT03929250
• Lead Sponsor: Oregon Health and Science University

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.

Study Timeline

• Study First Submitted: 2019-04-21
• Study First Submitted QC: 2019-04-25
• Study First Posted: 2019-04-26
• Study Start: 2019-07-05
• Primary Completion: 2019-11-30
• Study Completion: 2024-01-03
• Results First Submitted: 2024-01-04
• Status Verified: 2025-07
• Results First Submitted QC: 2025-07-18
• Last Update Submitted: 2025-07-18
• Results First Posted: 2025-08-06
• Last Update Posted: 2025-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
2g CAW Dose, then 4g CAW Dose	2g Centella asiatica water extract product	Participants first receive a single dose of a product containing 2g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of a product containing 4g CAW.
2g CAW Dose, then 4g CAW Dose	4g Centella asiatica water extract product	Participants first receive a single dose of a product containing 2g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of a product containing 4g CAW.
4g CAW Dose, then 2g CAW Dose	2g Centella asiatica water extract product	Participants first receive a single dose of a product containing 4g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of a product containing 2g CAW.
4g CAW Dose, then 2g CAW Dose	4g Centella asiatica water extract product	Participants first receive a single dose of a product containing 4g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of a product containing 2g CAW.

Primary Outcome Measures

Name	Time	Method
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).
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.
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).
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 Outcome Measures

Name	Time	Method
Pulse Rate	720 minutes after administration	Pulse rate will be measured peripherally over one minute.
Seated Diastolic Blood Pressure	720 minutes after administration	Seated blood pressure will be measured in millimeters mercury.
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 Systolic Blood Pressure	720 minutes after administration	Seated blood pressure will be measured in millimeters mercury.
Oral Temperature	720 minutes after administration	Oral temperature will be measured in degrees Fahrenheit by means of a thermometer.
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).
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.

Trial Locations

Locations (1)

Oregon Health and Science University Department of Neurology; 🇺🇸 Portland, Oregon, United States