Overview
This clinical trial is focused on determining whether biological signatures of target engagement by a Centella asiatica water extract product administered orally for 6 weeks can be measured in comparison to placebo. This study will also assess the safety and tolerability of the Centella asiatica water extract product.
Description
This Phase I study is a randomized, double-blind, placebo-controlled, clinical trial of 48 participants to evaluate safety, tolerability, and biological signatures of target engagement of brain neuronal viability, oxidative stress, and brain mitochondrial activity of a Centella asiatica water extract product (CAP) in older adults aged 60-85 years with mild cognitive impairment or mild Alzheimer's disease (AD). The intervention is taken orally daily for six weeks and pre and post assessments will be collected.
Eligibility
Inclusion criteria:
- Age 60-85, male and female
- Sufficient English language skills to complete all tests
- Sufficient vision and hearing to complete all tests
- No known allergies to Centella asiatica
- Absence of significant depression symptoms (Geriatric Depression Scale-15 score of < 5).
- Total score of <2 on the suicidal ideation subscale (measures 3, 7, 11, 12 and 14) of the Geriatric Depression Scale.
- Body Mass Index (BMI) greater than 17 and less than 35 at screening
- General health status that will not interfere with the ability to complete the study
- Willingness to discontinue all botanical dietary supplements for one week prior to and during the study.
- Willingness to undertake multiple MRI scans
- Meet the National Institute of Aging - Alzheimer's Association core clinical criteria for MCI or probable AD dementia with a Clinical Dementia Rating score of 0.5-1 and Mini Mental State Examination score of 20-28 at screening and baseline
- Participants who report a history of participative memory decline with gradual onset and slow progression over the last one year before screening MUST be corroborated by an informant.
- Participants on acetylcholinesterase inhibitor or memantine therapy for AD must be on a stable dose for at least 12 weeks prior to baseline visit.
- Participants must have an identified caregiver/study partner that can accompany participant to all study visits.
Exclusion criteria:
- Current smoking, alcohol, or substance abuse according to DSM-V criteria
- Women who are pregnant, planning to become pregnant, or breastfeeding
- Men who are actively trying to conceive a child or planning to within three months of study completion
- Severe aversion to venipuncture
- Abnormal labs indicating asymptomatic and untreated urinary tract infection
- Cancer within the last five years, with the exception of localized prostate cancer (Gleason Grade < 3) and non-metastatic skin cancers
- Comorbid conditions such as type I diabetes mellitus, poorly controlled type II diabetes mellitus (HbA1c > 7%), kidney failure, liver failure, hepatitis, blood disorders, clinical symptomatic orthostatic hypotension, and unstable or significantly symptomatic cardiovascular disease
- Significant disease of the Central Nervous System (CNS) such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke
- Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-V criteria
- Medications: anti-epileptics, sedatives, amitriptyline, anticoagulants (e.g., 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), beta blockers and anti-depressant medications that have not been at stable dosage for two months (including SSRIs, SNRIs)
- Non-Alzheimer dementia such as vascular dementia, normal pressure hydrocephalus, or Parkinson's disease
- MMSE score of < 20 or > 28
- Unwilling to maintain stable dosage of AD medications throughout study duration
- Unwilling to maintain stable dosage of intervention throughout the course of the study
- Contraindications to Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopic Imaging (MRSI) scans (some metal implants, pacemakers, claustrophobia)