Pharmacokinetics Centella Asiatica Product (CAP) in Mild Cognitive Impairment

• Status: Terminated
• Trial end date: 2020-12-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oregon Health and Science University
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Treatments: Cholinesterase Inhibitors

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.