Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment

NCT ID: NCT03937908

Last Updated: 2022-05-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-31
• Study Completion Date: 2020-12-21

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.

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.

Conditions

Cognitive Impairment; Elderly

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SCREENING
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

2g Centella asiatica water extract product

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

4g Centella asiatica water extract product

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

CAP 2g; CAP 4g

Eligibility 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.

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Amala Soumyanath

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amala Soumyanath, PhD

Role: PRINCIPAL_INVESTIGATOR

OHSU Department of Neurology

Locations

Oregon Health and Science University Department of Neurology

Portland, Oregon, United States

Countries

United States

References

Wright KM, McFerrin J, Alcazar Magana A, Roberts J, Caruso M, Kretzschmar D, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges. Front Nutr. 2022 Jan 14;8:799137. doi: 10.3389/fnut.2021.799137. eCollection 2021.

Reference Type: BACKGROUND

PMID: 35096945 (View on PubMed)

Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcazar Magana A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial. Antioxidants (Basel). 2022 Jan 23;11(2):215. doi: 10.3390/antiox11020215.

Reference Type: RESULT

PMID: 35204098 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R61AT009628

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00017985

Identifier Type: -

Identifier Source: org_study_id