Pharmacokinetics of Centella Asiatica in the Elderly

A Pharmacokinetic Study of Centella Asiatica in the Elderly

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Elderly
• Intervention / Treatment: Drug: 2g Centella asiatica water extract product; Drug: 4g Centella asiatica water extract product

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2g CAW Dose, then 4g CAW Dose; 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.	Drug: 2g Centella asiatica water extract product; 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.; Other Names: CAP 2g; Drug: 4g Centella asiatica water extract product; 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.; Other Names: CAP 4g
Experimental: 4g CAW Dose, then 2g CAW Dose; 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.	Drug: 2g Centella asiatica water extract product; 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.; Other Names: CAP 2g; Drug: 4g Centella asiatica water extract product; 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.; Other Names: CAP 4g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
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).	A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
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.	A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
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	A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Over 12 hours post-administration
Oral Temperature	Oral temperature will be measured in degrees Fahrenheit by means of a thermometer.	720 minutes after administration
Pulse Rate	Pulse rate will be measured peripherally over one minute.	720 minutes after administration
Seated Systolic Blood Pressure	Seated blood pressure will be measured in millimeters mercury.	720 minutes after administration
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).	720 minutes after administration
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.	0, 360 and 720 minutes after administration
Seated Diastolic Blood Pressure	Seated blood pressure will be measured in millimeters mercury.	720 minutes after administration

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Amala Soumyanath, PhD, OHSU Department of Neurology

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: April 21, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: STUDY00017697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results reported in a publication after de-identification.
• IPD Sharing Time Frame: Immediately after publication and for a period of 3 years following publication.
• IPD Sharing Access Criteria: Anyone who wishes access to the data, for any reason. Requests should be directed to Dr Amala Soumyanath at soumyana@ohsu.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No