Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 32 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Oregon, United States ) | NIH, U.S. Fed

Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03937908
Recruitment Status : Not yet recruiting
First Posted : May 6, 2019
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)
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 product (CAP) in mildly demented elders on cholinesterase inhibitor therapy. Compound levels will be measured in human plasma and urine over 12 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
Cognitive Impairment 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 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 12 hours after administration of each of the doses.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 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.
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
Estimated Study Start Date : August 1, 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 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 Name: 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 Name: CAP 4g




Primary Outcome Measures :
  1. Plasma concentration of Centella asiatica bioactive compounds [ 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 (tmax) [ 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. Half-life (t1/2) [ 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.

  3. Temporal changes in antioxidant 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.

  4. Urinary clearance [ 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.

  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.

  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.

  7. Seated blood pressure [ Time Frame: 0, 360 and 720 minutes after administration ]
    Seated blood pressure (systolic and diastolic) 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.

  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.

  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. PR interval length, QRS complex duration, and the QT interval will be measured in milliseconds. Each parameter will be compared to the value obtained at baseline (time 0, prior to intervention administration). For any differences seen from the baseline value, alternative clinical explanations will be considered in order to determine if the change is attributable to the study intervention.

  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.

  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.

  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03937908


Contacts
Layout table for location contacts
Contact: Amala Soumyanath, PhD 503-494-6878 soumyana@ohsu.edu

Locations
Layout table for location information
United States, Oregon
Oregon Health and Science University Department of Neurology Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Amala Soumyanath, PhD    503-494-6878    soumyana@ohsu.edu   
Contact: Kirsten Wright, ND    5034946882    wrigkir@ohsu.edu   
Principal Investigator: Amala Soumyanath, PhD         
Principal Investigator: Joseph Quinn, MD         
Sub-Investigator: Jodi Lapidus, PhD         
Sub-Investigator: Kirsten Wright, ND         
Sponsors and Collaborators
Oregon Health and Science University
National Center for Complementary and Integrative Health (NCCIH)
Investigators
Layout table for investigator information
Principal Investigator: Amala Soumyanath, PhD OHSU Department of Neurology

Layout table for additonal information
Responsible Party: Amala Soumyanath, Associate Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03937908     History of Changes
Other Study ID Numbers: STUDY00017985
R61AT009628 ( U.S. NIH Grant/Contract )
First Posted: May 6, 2019    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: ALL IPD that underlie results in a publication will be shared via a published journal article.
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs