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Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment

Sponsor
Oregon Health and Science University (Other)
Overall Status
Terminated
CT.gov ID
NCT03937908
Collaborator
National Center for Complementary and Integrative Health (NCCIH) (NIH)
5
Enrollment
1
Location
2
Arms
13.7
Actual Duration (Months)
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will measure the oral bioavailability and pharmacokinetics of known bioactive compounds from a standardized Centella asiatica water extract product (CAP) in mildly demented elders on cholinesterase inhibitor therapy. Compound levels will be measured in human plasma and urine over 10 hours after acute oral administration of two doses of the botanical extract product. The dose giving maximum plasma levels (Cmax)closest to those observed in the investigator's mouse studies, the area under the curve (AUC0-12), as well as the rate of clearance (t ½) of the known compounds and time of maximum concentration (tmax), will be identified. These data will be used to inform decisions on the dosage and dosing frequency for future clinical trials.

Condition or Disease Intervention/Treatment Phase
  • Drug: 2g Centella asiatica water extract product
  • Drug: 4g Centella asiatica water extract product
 Early Phase 1

Detailed Description

PRIMARY OBJECTIVES:

  1. To assess the bioavailability and rate of clearance of Centella asiatica derived compounds in mildly demented elders on cholinesterase inhibitor therapy through a pharmacokinetic study.

  2. To determine the acute tolerability of a Centella asiatica product in mildly demented elders on cholinesterase inhibitor therapy.

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 10 hours after administration of each of the doses.

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
This is an outpatient open-label clinical study using a blinded randomized crossover design of two doses.This is an outpatient open-label clinical study using a blinded randomized crossover design of two doses.
Masking:
Double (Participant, Outcomes Assessor)
Masking Description:
Randomization will use an arm equivalence design to promote equal numbers of participants for each order schema. All participants will be blinded to the dose they will be receiving at each visit. The investigators have developed a formulation that tastes and looks very similar at each dose. The investigator administering the intervention and the analyst performing the liquid chromatography analysis of collected plasma will be blinded as to the dose of the product administered. The liquid chromatography analyst will also be blinded as to the time point of collection.
Primary Purpose:
Screening
Official Title:
A Pharmacokinetic Study of Centella Asiatica Product (CAP) in Elderly Participants With Mild Cognitive Impairment Receiving Cholinesterase Inhibitor Therapy
Actual Study Start Date :
Oct 31, 2019
Actual Primary Completion Date :
Dec 21, 2020
Actual Study Completion Date :
Dec 21, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 2g CAP

Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.

Drug: 2g Centella asiatica water extract product
2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
Other Names:
  • CAP 2g

    		•
    Experimental: 4g CAP

    Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.

    Drug: 4g Centella asiatica water extract product
    4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Other Names:
  • CAP 4g

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax) [A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 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 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration) for each of the two doses (2g and 4g).

    2. Time of Maximum Concentration (Tmax) [A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480 and 600 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

    3. Half-life (t1/2) [A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480, and 600 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.

    Secondary Outcome Measures

    1. Area Under the Curve (AUC) of the Concentration vs Time Profiles of Known Bioactives From Centella Asiatica [A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480 and 600 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 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (area under the curve) for each of the two doses (2g and 4g).

    2. Total Urinary Excretion [Total 10 hours]

      All urine produced over the 10 hours post-administration was collected into a single container. The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) was measured in the single total urine sample collected over 10 hours after CAP administration. Urine samples were treated with glucuronidase and sulfatase enzymes to release analyte from conjugated (Phase II metabolite) forms of the analyte. All samples were analyzed using high performance liquid chromatography tandem mass spectrometry. The concentrations obtained were multiplied by total urine volume to obtain the total amount of that analyte excreted. The total amount (free and conjugated forms) in micrograms of of each analyte in the 10h urine sample is reported.

    3. NRF2 Expression [0, 1, 2, 3, 4, and 6h following study intervention]

      NRF2 gene expression was measured in peripheral blood mononuclear cells following consumption of 2g and 4g of Centella asiatica water extract product (CAP).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Age 65-85, male and female

    2. Meet the National Institute of Aging - Alzheimer's Association core clinical criteria for mild cognitive impairment or probable Alzheimer's disease dementia with a Clinical Dementia Rating (CDR) score of 0.5-1 and MMSE score of 20-28

    3. Report a history of subjective memory decline with gradual onset and slow progression over the last one year before screening; MUST be corroborated by an informant

    4. On cholinesterase inhibitor therapy for Alzheimer's disease (AD) and must be on a stable dose for at least 12 weeks prior to baseline

    5. Caregiver/study partner that can accompany participant to all study visits

    6. Sufficient English language skills to complete all tests

    7. Sufficient vision and hearing to complete all tests

    8. No known allergies to Centella asiatica or CAP excipients

    9. Willingness to discontinue all botanical dietary supplements for one week prior to and during each study visit

    10. Willingness to comply with a 48-hour low plant diet for each study visit

    11. Absence of significant depression symptoms (Geriatric Depression Scale-15 score of <12)

    12. Body Mass Index (BMI) greater than 17 and less than 35 at screening

    13. 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. Non-Alzheimer dementia such as vascular dementia, normal pressure hydrocephalus or Parkinson's disease

    12. Mini Mental State Examination (MMSE) score of <20 or >28 or CDR score >1 or zero

    13. Unwilling to maintain stable dosage of AD medications throughout study duration

    14. Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

    15. Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Oregon Health and Science University Department of Neurology Portland Oregon United States 97239

    Sponsors and Collaborators

    • Oregon Health and Science University
    • National Center for Complementary and Integrative Health (NCCIH)

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Amala Soumyanath, Associate Professor, Oregon Health and Science University
    ClinicalTrials.gov Identifier:
    NCT03937908
    Other Study ID Numbers:
    • STUDY00017985
    • R61AT009628
    First Posted:
    May 6, 2019
    Last Update Posted:
    May 4, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Cognitive Dysfunction

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Experimental: 2g CAP Then 4g CAP Experimental: 4g CAP Then 2g CAP
    Arm/Group Description Participants first received one single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. After a washout period of 14 days, they then received one single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Participants first received one single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. After a washout period of 14 days, they then received one single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Period Title: Overall Study
    STARTED 2 3
    COMPLETED 2 2
    NOT COMPLETED 0 1

    Baseline Characteristics

    Arm/Group Title All Participants
    Arm/Group Description Baseline values for all participants before randomization
    Overall Participants 5
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    0
    0%
    >=65 years
    5
    100%
    Sex: Female, Male (Count of Participants)
    Female
    2
    40%
    Male
    3
    60%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    5
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%
    Body mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    28
    (2)
    White blood cells (x10^3 cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^3 cells/uL]
    7.28
    (0.60)
    Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    132
    (7)
    Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    81
    (3)
    Body temperature (Celsius) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Celsius]
    36.7
    (0.1)
    Heart rate (beats per minute) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [beats per minute]
    68
    (5)
    Red blood cells (x10^6 cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^6 cells/uL]
    4.64
    (0.21)
    Hemoglobin (g/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/dL]
    14.3
    (0.6)
    Hematocrit (percentage) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage]
    44
    (2)
    Platelets (x10^3 platelets/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^3 platelets/uL]
    259
    (20)
    Blood glucose (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    81
    (3)
    Blood urea nitrogen (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    17
    (3)
    Creatinine (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.9
    (0.1)
    Total bilirubin (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.6
    (0.1)
    Aspartate aminotransferase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    26
    (3)
    Alanine aminotransferase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    32
    (3)
    Alkaline phosphatase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    87
    (12)
    Total protein (g/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/dL]
    7.7
    (0.1)
    Albumin (g/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/dL]
    3.8
    (0.1)
    Sodium (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    141
    (1)
    Chloride (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    108
    (1)
    Total CO^2 (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    29
    (1)
    Potassium (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    3.8
    (0.1)
    Calcium (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    9.3
    (0.1)
    Anion gap (mEq/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mEq/L]
    5
    (1)

    Outcome Measures

    1. Primary Outcome
    Title Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax)
    Description 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 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration) for each of the two doses (2g and 4g).
    Time Frame A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes).

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic parameter (Cmax) and time curves was calculated using non-compartmental analysis of plasma concentration versus time data using Excel software PK-solver (version 2.0).
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 4 4
    Asiatic acid
    124
    (29)
    259
    (24)
    Caffeic acid
    0.3
    (0.2)
    1
    (0.1)
    Dihydrocaffeic acid
    1
    (0.4)
    2
    (0.2)
    Dihydroferulic acid
    11
    (5)
    20
    (6)
    Dicaffeoylquinic acids
    18
    (10)
    3
    (0.3)
    Ferulic acid
    1
    (0.2)
    1.4
    (0.1)
    3-(3-hydroxyphenyl)propionic acid
    32
    (18)
    42
    (18)
    Isoferulic acid
    0.9
    (0.3)
    2
    (0.1)
    Madecassic acid
    38
    (3)
    63
    (10)
    Monocaffeoylquinic acids
    14
    (7)
    7
    (2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiatic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.01
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Caffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.23
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydrocaffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.001
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydroferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Ferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.07
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3-(3-hydroxyphenyl)propionic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.09
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Isoferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.10
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Monocaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.11
    Comments
    Method t-test, 2 sided
    Comments
    2. Primary Outcome
    Title Time of Maximum Concentration (Tmax)
    Description 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
    Time Frame A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480 and 600 minutes).

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 4 4
    Asiatic acid
    2
    (0.6)
    2
    (0.6)
    Caffeic acid
    4
    (2)
    4
    (1)
    Dihydrocaffeic acid
    3.25
    (0.5)
    3.5
    (0.5)
    Dihydroferulic acid
    3.4
    (1)
    3.5
    (0.5)
    Dicaffeoylquinic acids
    6
    (2)
    0.6
    (0.3)
    Ferulic acid
    5
    (0.6)
    5.5
    (0.5)
    3-(3-hydroxyphenyl)propionic acid
    6
    (1.4)
    5.5
    (1.7)
    Isoferulic acid
    1.3
    (0.6)
    1
    (0.4)
    Madecassic acid
    2
    (0.5)
    2
    (0.5)
    Monocaffeoylquinic acids
    4
    (2)
    2
    (0.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiatic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.82
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Caffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.40
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydrocaffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.20
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydroferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.48
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Ferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.20
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3-(3-hydroxyphenyl)propionic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.32
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Isoferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.35
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Monocaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.13
    Comments
    Method t-test, 2 sided
    Comments
    3. Primary Outcome
    Title Half-life (t1/2)
    Description 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.
    Time Frame A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480, and 600 minutes).

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 4 4
    Asiatic acid
    3.8
    (1)
    2.2
    (0.5)
    Caffeic acid
    2.6
    (1)
    3.5
    (1.2)
    Dihydrocaffeic acid
    4.8
    (1.3)
    1.1
    (0.4)
    Dihydroferulic acid
    4.5
    (1.6)
    2.5
    (0.3)
    Dicaffeoylquinic acids
    0
    (0)
    3
    (2)
    Ferulic acid
    13.4
    (5.3)
    7
    (1.2)
    3-(3-hydroxyphenyl)propionic acid
    2.3
    (0.3)
    1.8
    (0.7)
    Isoferulic acid
    8.8
    (5.7)
    2.9
    (0.6)
    Madecassic acid
    1.7
    (0.5)
    1.7
    (0.9)
    Monocaffeoylquinic acids
    2
    (0.5)
    3
    (0.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiatic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.34
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydrocaffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.08
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydroferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.23
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Ferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.14
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3-(3-hydroxyphenyl)propionic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.28
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Isoferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.98
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Monocaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.16
    Comments
    Method t-test, 2 sided
    Comments
    4. Secondary Outcome
    Title Area Under the Curve (AUC) of the Concentration vs Time Profiles of Known Bioactives From Centella Asiatica
    Description 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 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (area under the curve) for each of the two doses (2g and 4g).
    Time Frame A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480 and 600 minutes).

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 4 4
    Asiatic acid
    364
    (114)
    935
    (178)
    Caffeic acid
    1
    (1)
    3
    (0.3)
    Dihydrocaffeic acid
    3
    (0.4)
    6
    (1)
    Dihydroferulic acid
    42
    (18)
    77
    (25)
    Dicaffeoylquinic acids
    18
    (10)
    6
    (4)
    Ferulic acid
    7
    (2)
    10
    (1)
    3-(3-hydroxyphenyl)propionic acid
    100
    (46)
    189
    (77)
    Isoferulic acid
    5
    (2)
    8
    (0.4)
    Madecassic acid
    101
    (16)
    187
    (48)
    Monocaffeoylquinic acids
    18
    (6)
    23
    (4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiatic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.04
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Caffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.01
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydrocaffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.06
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydroferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.08
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dicaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.56
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Ferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.21
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3-(3-hydroxyphenyl)propionic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Isoferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.23
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Monocaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.16
    Comments
    Method t-test, 2 sided
    Comments
    5. Secondary Outcome
    Title Total Urinary Excretion
    Description All urine produced over the 10 hours post-administration was collected into a single container. The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) was measured in the single total urine sample collected over 10 hours after CAP administration. Urine samples were treated with glucuronidase and sulfatase enzymes to release analyte from conjugated (Phase II metabolite) forms of the analyte. All samples were analyzed using high performance liquid chromatography tandem mass spectrometry. The concentrations obtained were multiplied by total urine volume to obtain the total amount of that analyte excreted. The total amount (free and conjugated forms) in micrograms of of each analyte in the 10h urine sample is reported.
    Time Frame Total 10 hours

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 4 4
    Asiatic acid
    3
    (4)
    4
    (2)
    Dihydrocaffeic acid
    47
    (25)
    41
    (7)
    Dihydroferulic acid
    145
    (60)
    242
    (54)
    Ferulic acid
    18
    (6)
    24
    (5)
    3-(3-hydroxyphenyl)propionic acid
    16
    (10)
    13
    (7)
    Isoferulic acid
    18
    (6)
    24
    (5)
    Madecassic acid
    8
    (2)
    14
    (4)
    Monodicaffeoylquinic acids
    17
    (8)
    13
    (7)
    Madecassoside
    1
    (8)
    7
    (3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiatic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.7
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.09
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Asiaticoside
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.4
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Madecassoside
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.6
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Monocaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.4
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dicaffeoylquinic acids
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.1
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3-(3-hydroxyphenyl)propionic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.9
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Caffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.03
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Ferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.9
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Isoferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.6
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydroferulic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.4
    Comments
    Method t-test, 2 sided
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments Dihydrocaffeic acid
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.8
    Comments
    Method t-test, 2 sided
    Comments
    6. Secondary Outcome
    Title NRF2 Expression
    Description NRF2 gene expression was measured in peripheral blood mononuclear cells following consumption of 2g and 4g of Centella asiatica water extract product (CAP).
    Time Frame 0, 1, 2, 3, 4, and 6h following study intervention

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    Measure Participants 2 2
    0 h
    1
    (0)
    1
    (0)
    1 h
    2
    (0.2)
    2
    (0.3)
    2 h
    32
    (4)
    5
    (2)
    3 h
    22
    (9)
    3
    (1)
    4 h
    12
    (7)
    2
    (1)
    6 h
    4
    (2)
    1
    (0.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 1 hour
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.1
    Comments
    Method t-test, 1 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 2 hours
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.1
    Comments
    Method t-test, 1 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 3 hours
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.3
    Comments
    Method t-test, 1 sided
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 4 hours
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.5
    Comments
    Method t-test, 1 sided
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 2g CAP, 4g CAP
    Comments 6 hours
    Type of Statistical Test Equivalence
    Comments Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant.
    Statistical Test of Hypothesis p-Value 0.5
    Comments
    Method t-test, 1 sided
    Comments

    Adverse Events

    Time Frame Adverse events were collected during each study visit, 24 hours following study drug administration at each study visit, and 7 days after study visit two (end of study).
    Adverse Event Reporting Description Vital signs, EKG and CMP were monitored at baseline and during the visit. Adverse events were collected using a multi-system adverse events questionnaire during and after the visit.
    Arm/Group Title 2g CAP 4g CAP
    Arm/Group Description Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
    All Cause Mortality
    2g CAP 4g CAP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/4 (0%)
    Serious Adverse Events
    2g CAP 4g CAP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/4 (0%)
    Other (Not Including Serious) Adverse Events
    2g CAP 4g CAP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 4/4 (100%)
    Cardiac disorders
    Heart racing or irregular beating 1/4 (25%) 1 1/4 (25%) 1
    Hypertension/elevated blood pressure 1/4 (25%) 1 1/4 (25%) 1
    Eye disorders
    Blurred vision 1/4 (25%) 1 0/4 (0%) 0
    Gastrointestinal disorders
    Sore throat 0/4 (0%) 0 1/4 (25%) 1
    Increased appetite 1/4 (25%) 1 2/4 (50%) 2
    Dry mouth 0/4 (0%) 0 1/4 (25%) 1
    General disorders
    Generalized pain 1/4 (25%) 1 1/4 (25%) 1
    Immune system disorders
    Allergy symptoms 2/4 (50%) 2 0/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Inability to sit still 0/4 (0%) 0 1/4 (25%) 1
    Rigidity of any body part 0/4 (0%) 0 1/4 (25%) 1
    Nervous system disorders
    Headache 0/4 (0%) 0 1/4 (25%) 1
    Psychiatric disorders
    Anxiety 0/4 (0%) 0 1/4 (25%) 1
    Drowsiness 1/4 (25%) 1 1/4 (25%) 1
    Renal and urinary disorders
    Increased urination 0/4 (0%) 0 2/4 (50%) 2
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 1/4 (25%) 1 1/4 (25%) 1
    Skin and subcutaneous tissue disorders
    Sunburn or sensitivity of skin to light 0/4 (0%) 0 1/4 (25%) 1

    Limitations/Caveats

    Study was discontinued before the target number of participants were enrolled due to pandemic-related restrictions.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Amala Soumyanath
    Organization Oregon Health & Science University
    Phone 503-494-6878
    Email soumyana@ohsu.edu
    Responsible Party:
    Amala Soumyanath, Associate Professor, Oregon Health and Science University
    ClinicalTrials.gov Identifier:
    NCT03937908
    Other Study ID Numbers:
    • STUDY00017985
    • R61AT009628
    First Posted:
    May 6, 2019
    Last Update Posted:
    May 4, 2022
    Last Verified:
    Apr 1, 2022