Clinical trial NCT05591027: Safety and Target Engagement of Centella Asiatica in Cognitive Impairment
Official title: Safety and Target Engagement of Centella Asiatica in Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer's Disease
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
First posted: 2022-10-24
Enrollment: 48
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed 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 criteria: 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)

Primary outcomes:
measure: Change from baseline in brain N-acetylaspartate (NAA) to creatine (Cr) metabolite ratio (NAA/Cr) after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
Secondary outcomes:
measure: Change from baseline in urinary 8-hydroxy-2-deoxyguanosine (8 OHdG)/creatinine ratio after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in plasma 8-hydroxy-2-deoxyguanosine (8-OhdG) after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Adverse events (AE) arising during, and up to 4 weeks after, 6 weeks on intervention.
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks and 10 weeks
measure: Oral temperature measured at study visits.
timeFrame: Baseline and 6 weeks
measure: Pulse rate measured at study visits.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in seated blood pressure after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in body mass index after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in electrocardiography signals after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline liver function after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in kidney function after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
Other outcomes:
measure: Change from baseline in cortical and hippocampal levels of Adenosine triphosphate (ATP)/total phosphate after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in cortical and hippocampal levels of phosphocreatine (PCr)/total phosphate after 6 weeks on intervention.
timeFrame: Baseline and six weeks
measure: Change from baseline in cortical and hippocampal levels of inorganic phosphate (Pi)/total phosphate after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
measure: Change from baseline in cortical and hippocampal phosphocreatine/inorganic phosphate ratio (PCr/Pi) after 6 weeks on intervention.
timeFrame: Baseline and 6 weeks
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Amala Soumyanath, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Joseph Quinn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.