Safety, Tolerability, and Pharmacokinetics of an Oral Withania Somnifera Product in Older Adults
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Maximum Plasma Concentration (Cmax) 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 randomized, double-blind, crossover trial evaluating (a) the pharmacokinetics of withanolides from two doses (240 and 480 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. Participants will be randomized to one of two dose sequence groups. 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 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 (240 or 480 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
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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 240 mg
Participants will receive a single dose of 240 mg Shoden, administered as two 120 mg capsules, at pharmacokinetics visit 1 or 2 depending on their sequence group. Forty-eight hours later, participants will receive a 35-day supply of Shoden at a dose of 240 mg per day.
干预措施: Shoden (Dietary Supplement)
Shoden 480 mg
Participants will receive a single dose of 480 mg Shoden, administered as two 240 mg capsules, at pharmacokinetics visit 1 or 2 depending on their sequence group. Forty-eight hours later, participants will receive a 35-day supply of Shoden at a dose of 480 mg per day.
干预措施: Shoden (Dietary Supplement)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Withanolides After Shoden Administration
时间窗: For each study period, a 48-hour post-administration period (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 (240 or 480 mg), plasma concentrations of withanolides will be measured in plasma samples obtained over a 48-hour period, using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS) to determine pharmacokinetic parameters.
Plasma concentration of withanolides after Shoden administration
时间窗: For each study period, a 48-hour post-administration period (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 (240 or 480 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
- Number of participants with abnormal ECG readings(For each study period, electrocardiography will be assessed at 0 and 420 minutes post-Shoden administration and at the four week follow-up visit)
- Liver function(For each study period, liver function will be assessed at 0 and 600 minutes post-Shoden administration, and at the four-week follow-up visit)
- White blood cell count(For each study period, white blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Red blood cell count(For each study period, red blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Adverse events(For each study period, adverse events will be assessed at the beginning and end of each pharmacokinetics visit, 2-weeks post-administration, and 4-weeks post-administration.)
- Time of maximum concentration of withanolides after Shoden administration(For each study period, a 48-hour post-administration period (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, a 48-hour post-administration period (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(For each study period, steady state concentration will be collected during week 4 following four weeks' daily use of Shoden.)
- Thyroid-stimulating hormone(For each study period, thyroid-stimulating hormone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Urine concentration of withanolides after Shoden administration(For each study period, over 12 hours post-Shoden administration, 24-hour sample, 48-hour sample, four-week sample)
- Testosterone(For each study period, testosterone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Hematocrit(For each study period, hematocrit will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Kidney function(For each study period, liver function will be assessed at 0 and 600 minutes post-Shoden administration, and at the four-week follow-up visit)
- Hemoglobin(For each study period, hemoglobin will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Feasibility of administering REDCap surveys(For each study period, prior to the pharmacokinetics visit and prior to the four-week follow-up visit)
- Time of Maximum Concentration of Withanolides After Shoden Administration(For each study period, a 48-hour post-administration period (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, a 48-hour post-administration period (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(For each study period, steady state concentration will be collected during week 4 following four weeks' daily use of Shoden.)
- Urine Concentration of Withanolides After Shoden Administration(For each study period, urine collected over the first 12 hours post-Shoden administration.)
- Number of Participants With Abnormal ECG Readings (7 Hours)(For each study period, electrocardiography will be assessed at 0 and 7 hours post-Shoden administration. For pharmacokinetics visits that were halted early, ECG was collected at 24 hours.)
- Number of Participants With Abnormal ECG Readings (4 Weeks)(For each study period, electrocardiography will be assessed at 0 and 4 weeks post-Shoden administration.)
- Mean Change in ALT (10 Hours)(For each study period, liver function will be assessed at 0 and 10 hours post-Shoden administration. For pharmacokinetics visits that were halted early, safety labs were collected at 24 hours.)
- Mean Change in ALT (4 Weeks)(For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration.)
- Mean Change in AST (10 Hours)(For each study period, liver function will be assessed at 0 and 10 hours post-Shoden administration. For pharmacokinetics visits that were halted early, safety labs were collected at 24 hours.)
- Mean Change in AST (4 Weeks)(For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration.)
- Mean Change in Creatinine (10 Hours)(For each study period, liver function will be assessed at 0 and 10 hours post-Shoden administration. For pharmacokinetics visits that were halted early, safety labs were collected at 24 hours.)
- Mean Change in Creatinine (4 Weeks)(For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration.)
- Mean Change in Thyroid-stimulating Hormone (4 Weeks)(For each study period, thyroid-stimulating hormone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Mean Change in Testosterone (4 Weeks)(For each study period, testosterone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Mean White Blood Cell Count (4 Weeks)(For each study period, white blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Mean Change in Red Blood Cell Count (4 Weeks)(For each study period, red blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Mean Change in Hemoglobin (4 Weeks)(For each study period, hemoglobin will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Mean Change in Hematocrit (4 Weeks)(For each study period, hematocrit will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.)
- Percentage of REDCap Surveys Completed(For each study period, prior to the pharmacokinetics visit and prior to the four-week follow-up visit)
研究者
Alex Speers, ND
Assistant Professor
Oregon Health and Science University