Pharmacokinetics of Centella Asiatica in the Elderly

November 1, 2023 updated by: Amala Soumyanath, Oregon Health and Science University

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2g CAW Dose
2g of Centella asiatica water extract in a standardized product.
2g Centella asiatica water extract product is a powder containing Centella asiatica water extract 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
Experimental: 4g CAW Dose
4g of Centella asiatica water extract in a standardized product.
4g Centella asiatica water extract product is a powder containing Centella asiatica water extract 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
Human plasma concentration of bioactives from Centella asiatica.
Time Frame: 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).
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
Time of maximum concentration
Time Frame: 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
A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
Temporal changes in anti-oxidant status
Time Frame: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
Ferric reducing ability of plasma (FRAP) will be measured in the plasma collected at each time point to generate a graph of antioxidant potential over time.
A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
Urinary excretion
Time Frame: 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.
Over 12 hours post-administration
Half-life
Time Frame: 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 and their metabolites will be 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).
Oral temperature
Time Frame: 0, 360 and 720 minutes after administration
Oral temperature will be measured in degrees Celsius by means of a thermometer. Temperatures falling outside the normal range (33.2-38.2 degrees Celsius) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will also determine the proportion of all participants who develop changes in temperature following administration of CAP.
0, 360 and 720 minutes after administration
Pulse rate
Time Frame: 0, 360 and 720 minutes after administration
Pulse rate will be measured peripherally over one minute. Pulse rates falling outside the normal range (60-80 beats per minute) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will also determine the proportion of all participants who develop changes in pulse rate following administration of CAP.
0, 360 and 720 minutes after administration
Seated blood pressure
Time Frame: 0, 360 and 720 minutes after administration
Seated blood pressure will be measured in millimeters mercury. Blood pressure readings falling outside the normal range (90-130/60-80 millimeters Mercury) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will also determine the proportion of all participants who develop changes in blood pressure following administration of CAP.
0, 360 and 720 minutes after administration
Body mass index
Time Frame: 0, 360 and 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). Changes in body mass index greater than two kilograms per meter squared from baseline levels, along with consideration of alternative clinical explanations, will be used to determine attribution to the study intervention. The investigators will also determine the proportion of all participants who develop changes in body mass index of greater than two units (kilograms per meter squared) following administration of CAP.
0, 360 and 720 minutes after administration
Electrocardiography
Time Frame: 0, 360 and 720 minutes after administration
Resting electrocardiography will be measured for up to five minutes using a five lead mobile electrocardiogram. Changes in P wave shape or length, QRS complex shape or length, and QT interval from the zero minute (baseline) timepoint will be measured, and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The investigators will also determine the proportion of all participants who develop changes in electrocardiography compared to the zero minute timepoint following CAP administration.
0, 360 and 720 minutes after administration
Liver function
Time Frame: 0, 360 and 720 minutes after administration
A comprehensive metabolic panel will measure alanine aminotransferase and aspartate aminotransferase in units per liter as markers of liver function. Enzyme levels falling outside the normal range (0-35 Units per liter for alanine aminotransferase and 17-59 Units per liter for aspartate aminotransferase) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. The investigators will aggregate the measures by using an elevation in either enzyme function as a reflection of overall liver function. The investigators will also determine the proportion of all participants who develop abnormal laboratory values following administration of CAP.
0, 360 and 720 minutes after administration
Kidney function
Time Frame: 0, 360 and 720 minutes after administration
A comprehensive metabolic panel will measure creatinine and blood urea nitrogen levels in milligrams per deciliter as markers of kidney function. Each parameter falling outside the normal range ( 0.5 to 1.2 milligrams per deciliter for creatinine and 7 to 20 milligrams per deciliter for blood urea nitrogen), will be compared to baseline values and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. The investigators will aggregate the measures by using an elevation in either blood urea nitrogen or creatinine as a reflection of overall kidney function. The investigators will also determine the proportion of all participants who develop abnormal laboratory values following administration of CAP.
0, 360 and 720 minutes after administration
Adverse events
Time Frame: 0, 6, 12 and 24 hours after administration
A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events. The Investigators will evaluate any changes in symptoms from baseline, and consider alternative clinical explanations, to determine if the changes are adverse events attributable to the study intervention. The investigators will determine the proportion of participants who report each type of adverse event following administration of CAP.
0, 6, 12 and 24 hours after administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Amala Soumyanath, PhD, OHSU Department of Neurology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2019

Primary Completion (Actual)

November 30, 2019

Study Completion (Estimated)

December 1, 2023

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 (Estimated)

November 3, 2023

Last Update Submitted That Met QC Criteria

November 1, 2023

Last Verified

November 1, 2023

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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