Safety and Target Engagement of Centella Asiatica in Cognitive Impairment

NCT05591027 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17767
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change from baseline in brain N-acetylaspartate (NAA) to creatine (Cr) metabolite ratio (NAA/Cr) after 6 weeks on intervention.

  N-acetylaspartate (NAA)/creatine (Cr) metabolite ratio (NAA/Cr) in the brain determined through 1H-Magnetic Resonance Spectroscopic Imaging of a single brain slice as an indicator of neuronal viability and mitochondrial activity.

  Baseline and 6 weeks

Secondary Outcomes (10)

• Change from baseline in urinary 8-hydroxy-2-deoxyguanosine (8 OHdG)/creatinine ratio after 6 weeks on intervention.

  Baseline and 6 weeks

• Change from baseline in plasma 8-hydroxy-2-deoxyguanosine (8-OhdG) after 6 weeks on intervention.

  Baseline and 6 weeks

• Adverse events (AE) arising during, and up to 4 weeks after, 6 weeks on intervention.

  Baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks and 10 weeks

• Oral temperature measured at study visits.

  Baseline and 6 weeks

• Pulse rate measured at study visits.

  Baseline and 6 weeks

Other Outcomes (4)

• Change from baseline in cortical and hippocampal levels of Adenosine triphosphate (ATP)/total phosphate after 6 weeks on intervention.

  Baseline and 6 weeks

• Change from baseline in cortical and hippocampal levels of phosphocreatine (PCr)/total phosphate after 6 weeks on intervention.

  Baseline and six weeks

• Change from baseline in cortical and hippocampal levels of inorganic phosphate (Pi)/total phosphate after 6 weeks on intervention.

  Baseline and 6 weeks

Study Arms (2)

Centella asiatica water extract product (CAP) 4g

EXPERIMENTAL

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.

Drug: Centella asiatica product

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Centella asiatica product DRUG

A sachet of powdered product containing 4 g of a dried hot water extract of Centella asiatica as the active ingredient, combined with inactive ingredients (excipients) for color and taste dissolved in 10 oz of warm or room temperature water and consumed orally.

Also known as: CAP

Centella asiatica water extract product (CAP) 4g

Placebo DRUG

A sachet of powdered inactive ingredients (excipients) for color and taste identical in volume to those found in the active arm (CAP) dissolved in 10 oz of warm or room temperature water and consumed orally.

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Alzheimer's Association: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 35096945 BACKGROUND

• 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.

  PMID: 35204098 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Amala Soumyanath, Ph.D

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

• Joseph Quinn, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amala Soumyanath, PhD

CONTACT

503-494-6878; soumyana@ohsu.edu

Lucy Allison, MS

CONTACT

503-418-8197; allisolu@ohsu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Drug product and placebo will be prepared at Oregon's Wild Harvest using a formula that matches taste, smell, and appearance. The Research Pharmacy at Oregon Health and Science University will maintain information on product allocation (drug or placebo) to individual participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 48 participants will be randomized to receive either Centella asiatica water extract product (CAP) or placebo treatment. Participants will be stratified by sex so that CAP and placebo arms have equal numbers of each sex.

Study Record Dates

• First Submitted: October 16, 2022
• First Posted: October 24, 2022
• Study Start: December 1, 2022
• Primary Completion: November 30, 2025
• Study Completion: March 31, 2026
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)