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Pharmacokinetics of Centella Asiatica in the Elderly

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ClinicalTrials.gov Identifier: NCT03929250
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Amala Soumyanath, Oregon Health and Science University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Elderly 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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomization will use an arm equivalence design to promote equal numbers of participants for each order schema.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Screening
Official Title: A Pharmacokinetic Study of Centella Asiatica in the Elderly
Actual Study Start Date : July 5, 2019
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : November 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drinking Water

Arm Intervention/treatment
Experimental: 2g CAW Dose
2g of Centella asiatica water extract in a standardized product.
Drug: 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.
Other Name: CAP 2g

Experimental: 4g CAW Dose
4g of Centella asiatica water extract in a standardized product.
Drug: 4g Centella asiatica water extract 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 Name: CAP 4g




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929250


Contacts
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Contact: Amala Soumyanath, PhD 503-494-6878 soumyana@ohsu.edu
Contact: Kirsten Wright, ND 503-494-6882 wrigkir@ohsu.edu

Locations
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United States, Oregon
Oregon Health and Science University Department of Neurology Recruiting
Portland, Oregon, United States, 97239
Contact: Amala Soumyanath, PhD    503-494-6878    soumyana@ohsu.edu   
Contact: Kirsten Wright, ND    5034946882    wrigkir@ohsu.edu   
Sub-Investigator: Joseph Quinn, MD         
Principal Investigator: Amala Soumyanath, PhD         
Sub-Investigator: Kirsten Wright, ND         
Sub-Investigator: Jodi Lapidus, PhD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
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Principal Investigator: Amala Soumyanath, PhD OHSU Department of Neurology

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Responsible Party: Amala Soumyanath, Associate Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03929250     History of Changes
Other Study ID Numbers: STUDY00017697
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results reported in a publication after de-identification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: Immediately after publication and for a period of 3 years following publication.
Access Criteria: Anyone who wishes access to the data, for any reason. Requests should be directed to Dr Amala Soumyanath at soumyana@ohsu.edu

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No