Safety and Target Engagement of Centella Asiatica in Cognitive Impairment

Oregon Health & Science University (OHSU)

Status and phase: Enrolling; Phase 1

Conditions: Alzheimer's Disease; Mild Cognitive Impairment

Treatments: Drug: Placebo; Drug: Centella asiatica product

Study type: Interventional

Funder types: Other

Identifiers

NCT05591027

17767

Details and patient eligibility

About

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.

Full 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 65-85 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.

Enrollment: 48 estimated patients

Sex: All

Ages: 65 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 65-85, 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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48 participants in 2 patient groups, including a placebo group

Centella asiatica water extract product (CAP) 4g

Experimental group

Description:

A sachet of containing 4g dried hot water extract (CAW) of Centella asiatica combined with inactive ingredients (excipients) will be dissolved in water and orally consumed daily as a drink for six weeks. Assessments will be collected at baseline and after six weeks of daily intervention.

Treatment:

Drug: Centella asiatica product

Placebo

Placebo Comparator group

Description:

A sachet of inactive ingredients (excipients) identical in composition to those found in the active arm will be be dissolved in water and orally consumed daily for six weeks. Assessments will be collected at baseline and after six weeks of daily intervention.

Treatment:

Drug: Placebo