Safety, Tolerability, and Pharmacokinetics of an Oral Withania Somnifera Product in Older Adults
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Plasma concentration of withanolides after Shoden administration
研究概览
简要总结
This study will measure the oral bioavailability and pharmacokinetics of known compounds from a standardized Withania somnifera botanical dietary supplement in healthy older adults.
详细描述
This is a single-blind, crossover trial evaluating (a) the pharmacokinetics of withanolides from two doses (120 and 240 mg) of a commercially available Withania somnifera root and leaf extract (Shoden®), (b) the safety and tolerability of these doses over four weeks' use and (c) the feasibility of remotely measuring sleep- and stress-related outcomes in older adults. There will be two four-week study periods separated by a two-week washout period. During each study period, participants will attend a 13-hour pharmacokinetics study visit, where they will receive a single dose of either 120 or 240 mg Shoden®, and return for 24- and 48-hour blood and urine collections. After the 48-hour visit, they will continue taking Shoden® at the administered dose (120 or 240 mg) for four weeks, at which time they will return for a follow-up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participants will not be told the order in which they receive 120 or 240 mg of the study agent, but every participant will receive 120 mg during the first study period and 240 mg during the second study period. This was done to prevent anticipation of more side effects at the higher dose of the study agent.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 65 and older, male and female
- •Body Mass Index (BMI) greater than 17 and less than 35 at screening
- •Sufficient vision and hearing to complete all tests
- •Willingness to discontinue all botanical supplementation for one week prior to and throughout study
- •No known sensitivity to Withania somnifera or any of its derivatives
- •Normal or clinically not significant 12-lead electrocardiogram (ECG) recording
- •Hepatic (ALT, AST, bilirubin), renal (creatinine, estimated GFR), and TSH parameters within normal range
- •Hemoglobin ≥13.0 g/dL or hematocrit ≥39% (males) OR hemoglobin ≥12.5 g/dL or hematocrit ≥38% (females), per FDA recommendations on blood donation
- •General health status that will not interfere with the ability to complete the study
- •Willingness to attend all study visits
- •Willingness to avoid caffeine and xanthine-containing foods or beverages (e.g., coffee, tea, chocolate, caffeine-containing sodas, colas, etc.), as well as grapefruit juice and poppy-containing foods for 48 hours prior to baseline visits
- •Willingness to adhere to special diet (no dairy, grapefruit products, poppy-containing foods, high-fat meals, caffeine, or xanthine-containing foods or beverages) during baseline visits and until after 24-hour visit
- •Mini-Mental State Exam (MMSE) score ≥26
排除标准
- •Current smoking, alcohol, or substance abuse according to DSM-V criteria
- •Participants who are currently pregnant, actively trying to conceive a child, or planning to within three months of study completion
- •Severe aversion to venipuncture
- •Donation of blood within 90 days of screening
- •Participation in drug research study within 90 days of screening
- •Serious health condition (i.e., illness, injury, impairment, or physical or mental condition which requires a) overnight hospitalization or b) continuing treatment that may cause episodic periods of incapacity of more than 3 consecutive days) within 30 days of screening
- •Allergy to nightshade plants (Solanaceae family)
- •Abnormal labs indicating symptomatic and untreated urinary tract infection
- •History of prostate cancer
- •History of kidney transplant
- •Cancer within the last five years, with the exception of non-metastatic skin cancers
- •Comorbid conditions requiring medication such as diabetes, kidney failure, liver failure, hepatitis, blood disorders, hypotension, thyroid disease, respiratory disorders, or cardiovascular disease
- •Presence of sleep apnea, moderate to severe restless leg syndrome, major circadian rhythm changes, or narcolepsy
- •Significant disease of the Central Nervous System (CNS) such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke
- •Diagnosis of major depression, schizophrenia, bipolar disorder, or other major psychiatric disorder as defined by DSM-V criteria
- •Diseases associated with dementia such as Alzheimer's disease, vascular dementia, normal pressure hydrocephalus or Parkinson's disease
研究组 & 干预措施
Shoden 120 mg
Shoden, administered as a single 120 mg capsule, once at the pharmacokinetics visit and once daily for four weeks following the 48 hour visit.
干预措施: Shoden (Dietary Supplement)
Shoden 240 mg
Shoden, administered as a single 240 mg capsule, once at the pharmacokinetics visit and once daily for four weeks following the 48 hour visit.
干预措施: Shoden (Dietary Supplement)
结局指标
主要结局
Plasma concentration of withanolides after Shoden administration
时间窗: For each study period, collected over a 48-hour post-administration period (0 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 24 hours, and 48 hours)
After oral administration of Shoden (120 or 240 mg), plasma concentrations of eleven withanolides (withanolide A, withanolide B, withaferin A, withanone, withanoside IV, withanoside V, 12-deoxywithastramonolide, sominone, viscosalactone B, 4-oxo withaferin A, and 2,3-dihydro-3β-methoxy withaferin-A) will be measured in blood samples obtained over a 48-hour period, using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS) to determine pharmacokinetic parameters (maximum concentration, area under the curve(0-t), and area under the curve(0-infinity)).
次要结局
- Time of maximum concentration of withanolides after Shoden administration(For each study period, collected over a 48-hour post-administration period (0 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 24 hours, and 48 hours))
- Half-life of withanolides after Shoden administration(For each study period, collected over a 48-hour post-administration period (0 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 24 hours, and 48 hours))
- Steady-state concentration of selected withanolides in plasma(At four weeks for each study period)
- Urine concentration of withanolides after Shoden administration(For each study period, collected from 0-12 hours, 24 hours, and 48 hours of each pharmacokinetics visit, and at four weeks)
- Adverse events(For each study period, baseline and 12 hours of each pharmacokinetics visit, and at 2 weeks and 4 weeks. Also collected at 2 weeks post-study completion.)
- Number of participants with abnormal ECG readings(For each study period, baseline (0 hours) and 7 hours of each pharmacokinetics visit, and at 4 weeks.)
- Liver function(For each study period, baseline (0 hours) and at 10 hours of each pharmacokinetics visit, and at 4 weeks)
- Kidney function(For each study period, baseline (0 hours) and at 10 hours of each pharmacokinetics visit, and at 4 weeks)
- Thyroid-stimulating hormone(For each study period, baseline and at 4 weeks)
- Testosterone(For each study period, baseline and at 4 weeks)
- White blood cell count(For each study period, baseline and at 4 weeks)
- Red blood cell count(For each study period, baseline and at 4 weeks)
- Hemoglobin(For each study period, baseline and at 4 weeks)
- Hematocrit(For each study period, baseline and at 4 weeks)
- Feasibility of administering REDCap surveys(For each study period, baseline and at 4 weeks)
研究者
Alex Speers, ND
Assistant Professor
Oregon Health and Science University