Pharmacokinetics of Centella Asiatica in the Elderly | NCT03929250

NCT03929250

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
2g CAW Dose, then 4g CAW Dose	Experimental	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 Drug: 4g Centella asiatica water extract product
4g CAW Dose, then 2g CAW Dose	Experimental	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 Drug: 4g Centella asiatica water extract product

Interventions

Name	Type	Description	Arm Group Labels	Other Names
2g Centella asiatica water extract product	Drug	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.

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 65-85, male and female
Sufficient English language skills to complete all tests
Sufficient vision and hearing to complete all tests
No known allergies to Centella asiatica or CAP components
Willingness to discontinue all botanical dietary supplements for one week prior to and during each study visit
Willingness to comply with a 48-hour low plant diet for each study visit
Absence of significant depression symptoms (Geriatric Depression Scale-15 score of <12)
Body Mass Index (BMI) greater than 17 and less than 35 at screening
Non-demented, defined as Clinical Dementia Rating (CDR) score of zero and Mini Mental State Examination (MMSE) score >28
General health status that will not interfere with the ability to complete the study

Exclusion Criteria:

Current smoking, alcohol or substance abuse according to DSM-V criteria
Women who are pregnant, planning to become pregnant or breastfeeding
Men who are actively trying to conceive a child or planning to within three months of study completion
Severe aversion to venipuncture
Abnormal laboratory evaluation indicating asymptomatic and untreated urinary tract infection
Cancer within the last five years, with the exception of localized prostate cancer (Gleason Grade <3) and non-metastatic skin cancers
Comorbid conditions such as diabetes mellitus, kidney failure, liver failure, hepatitis, blood disorders, clinical symptomatic orthostatic hypotension, and unstable or significantly symptomatic cardiovascular disease
Significant disease of the central nervous system such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke
Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-V criteria
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)
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
Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

Name	Affiliation	Role
Amala Soumyanath, PhD	OHSU Department of Neurology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Oregon Health and Science University Department of Neurology		Portland	Oregon	97239	United States

IPD Sharing Statement Module

ID	Title	Description
FG000	2g CAW Dose, Then 4g CAW Dose	Participants first receive a single dose of product containing 2g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 4g CAW.
FG001	4g CAW Dose, Then 2g CAW Dose	Participants first receive a single dose of product containing 4g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 2g CAW.

Baseline Characteristics Module

ID	Title	Description
BG000	All Participants	All participants including those in the (a) 2g CAW, then 4g CAW arm or (b) 4g CAW then 2g CAW arm

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

Posted

Mean

Standard Error

ng/mL

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

ID	Title	Description
OG000	2g CAW Dose	2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	2g CAW Dose	2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract 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.