Safety and Target Engagement of Centella Asiatica in Cognitive Impairment

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Centella asiatica product
  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.
• Препарат Placebo
  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.

Первичные конечные точки

• Change from baseline in brain N-acetylaspartate (NAA) to creatine (Cr) metabolite ratio (NAA/Cr) after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]

Вторичные конечные точки (10)

• Change from baseline in urinary 8-hydroxy-2-deoxyguanosine (8 OHdG)/creatinine ratio after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Change from baseline in plasma 8-hydroxy-2-deoxyguanosine (8-OhdG) after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Adverse events (AE) arising during, and up to 4 weeks after, 6 weeks on intervention. [Срок оценки: Baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks and 10 weeks]
• Oral temperature measured at study visits. [Срок оценки: Baseline and 6 weeks]
• Pulse rate measured at study visits. [Срок оценки: Baseline and 6 weeks]
• Change from baseline in seated blood pressure after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Change from baseline in body mass index after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Change from baseline in electrocardiography signals after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Change from baseline liver function after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]
• Change from baseline in kidney function after 6 weeks on intervention. [Срок оценки: Baseline and 6 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Oregon Health & Science University — Portland

Публикации

• 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
• 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

Идентификаторы

NCT: NCT05591027 · 17767

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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