A Pharmacokinetic Study of Centella Asiatica Product (CAP) in Elderly Participants With Mild Cognitive Impairment Receiving Cholinesterase Inhibitor Therapy
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax)
研究概览
简要总结
This study will measure the oral bioavailability and pharmacokinetics of known bioactive compounds from a standardized Centella asiatica water extract product (CAP) in mildly demented elders on cholinesterase inhibitor therapy. Compound levels will be measured in human plasma and urine over 10 hours after acute oral administration of two doses of the botanical extract product. The dose giving maximum plasma levels (Cmax)closest to those observed in the investigator's mouse studies, the area under the curve (AUC0-12), as well as the rate of clearance (t ½) of the known compounds and time of maximum concentration (tmax), will be identified. These data will be used to inform decisions on the dosage and dosing frequency for future clinical trials.
详细描述
PRIMARY OBJECTIVES:
- To assess the bioavailability and rate of clearance of Centella asiatica derived compounds in mildly demented elders on cholinesterase inhibitor therapy through a pharmacokinetic study.
- To determine the acute tolerability of a Centella asiatica product in mildly demented elders on cholinesterase inhibitor therapy.
OUTLINE:
Participants will orally consume a single administration of a standardized Centella asiatica water extract product (CAP). Two doses (2g and 4g CAW) will be administered on separate occasions, at least two weeks apart. The levels of known bioactive compounds present in Centella asiatica will be measured in human plasma and urine over 10 hours after administration of each of the doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Screening
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Randomization will use an arm equivalence design to promote equal numbers of participants for each order schema. All participants will be blinded to the dose they will be receiving at each visit. The investigators have developed a formulation that tastes and looks very similar at each dose. The investigator administering the intervention and the analyst performing the liquid chromatography analysis of collected plasma will be blinded as to the dose of the product administered. The liquid chromatography analyst will also be blinded as to the time point of collection.
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 65-85, male and female
- •Meet the National Institute of Aging - Alzheimer's Association core clinical criteria for mild cognitive impairment or probable Alzheimer's disease dementia with a Clinical Dementia Rating (CDR) score of 0.5-1 and MMSE score of 20-28
- •Report a history of subjective memory decline with gradual onset and slow progression over the last one year before screening; MUST be corroborated by an informant
- •On cholinesterase inhibitor therapy for Alzheimer's disease (AD) and must be on a stable dose for at least 12 weeks prior to baseline
- •Caregiver/study partner that can accompany participant to all study visits
- •Sufficient English language skills to complete all tests
- •Sufficient vision and hearing to complete all tests
- •No known allergies to Centella asiatica or CAP excipients
- •Willingness to discontinue all botanical dietary supplements for one week prior to and during each study visit
- •Willingness to comply with a 48-hour low plant diet for each study visit
- •Absence of significant depression symptoms (Geriatric Depression Scale-15 score of <12)
- •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
排除标准
- •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 laboratory evaluation 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 diabetes mellitus, 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 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: sedatives (except those used occasionally for sleep), central nervous system active medications that have not been stable for two months (including beta blockers, cimetidine, SSRIs, SNRIs), anticoagulants (i.e. 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)
- •Non-Alzheimer dementia such as vascular dementia, normal pressure hydrocephalus or Parkinson's disease
- •Mini Mental State Examination (MMSE) score of <20 or >28 or CDR score >1 or zero
- •Unwilling to maintain stable dosage of AD medications throughout study duration
- •Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- •Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
研究组 & 干预措施
2g CAP
Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
干预措施: 2g Centella asiatica water extract product (Drug)
4g CAP
Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
干预措施: 4g Centella asiatica water extract product (Drug)
结局指标
主要结局
Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax)
时间窗: A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes).
Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration) for each of the two doses (2g and 4g).
Half-life (t1/2)
时间窗: A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480, and 600 minutes).
The half-life (t1/2) of the known bioactive compounds and their metabolites will be calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals.
Time of Maximum Concentration (Tmax)
时间窗: A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480 and 600 minutes).
The time of maximum concentration (Tmax) of the known bioactive compounds and their metabolites will be calculated from the concentrations measured by high performance liquid chromatography tandem mass spectrometry in order to help determine dosage intervals
次要结局
- Area Under the Curve (AUC) of the Concentration vs Time Profiles of Known Bioactives From Centella Asiatica(A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480 and 600 minutes).)
- Total Urinary Excretion(Total 10 hours)
- NRF2 Expression(0, 1, 2, 3, 4, and 6h following study intervention)
研究者
Amala Soumyanath
Associate Professor
Oregon Health and Science University