- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03929250
Pharmacokinetics of Centella Asiatica in the Elderly
A Pharmacokinetic Study of Centella Asiatica in the Elderly
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
- 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.
- 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
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University Department of Neurology
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
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:
|
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:
|
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).
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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).
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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
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A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
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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).
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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.
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A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).
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Urinary excretion
Time Frame: Over 12 hours post-administration
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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.
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Over 12 hours post-administration
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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.
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0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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Body mass index
Time Frame: 0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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Kidney function
Time Frame: 0, 360 and 720 minutes after administration
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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.
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0, 360 and 720 minutes after administration
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Adverse events
Time Frame: 0, 6, 12 and 24 hours after administration
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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.
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0, 6, 12 and 24 hours after administration
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Collaborators and Investigators
Investigators
- Principal Investigator: Amala Soumyanath, PhD, OHSU Department of Neurology
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
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)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
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
Studies a U.S. FDA-regulated device product
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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