Clinical trial NCT06171724: Ashwagandha Pharmacokinetics Study in Older Adults
Official title: Safety, Tolerability, and Pharmacokinetics of an Oral Withania Somnifera Product in Older Adults
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: EARLY_PHASE1
Conditions: Healthy
Aging
Keywords: Withania
Herbal Medicine
Dietary Supplements
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2023-12-15
Enrollment: 12
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study will measure the oral bioavailability and pharmacokinetics of known compounds from a standardized Withania somnifera botanical dietary supplement in healthy older adults.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 65 and older, male and female
2. Body Mass Index (BMI) greater than 17 and less than 35 at screening
3. Sufficient vision and hearing to complete all tests
4. Willingness to discontinue all botanical supplementation for one week prior to and throughout study
5. No known sensitivity to Withania somnifera or any of its derivatives
6. Normal or clinically not significant 12-lead electrocardiogram (ECG) recording
7. Hepatic (ALT, AST, bilirubin), renal (creatinine, estimated GFR), and TSH parameters within normal range
8. 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
9. General health status that will not interfere with the ability to complete the study
10. Willingness to attend all study visits
11. 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
12. 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
13. Mini-Mental State Exam (MMSE) score ≥26

Exclusion Criteria:

1. Current smoking, alcohol, or substance abuse according to DSM-V criteria
2. Participants who are currently pregnant, actively trying to conceive a child, or planning to within three months of study completion
3. Severe aversion to venipuncture
4. Donation of blood within 90 days of screening
5. Participation in drug research study within 90 days of screening
6. 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
7. Allergy to nightshade plants (Solanaceae family)
8. Abnormal labs indicating symptomatic and untreated urinary tract infection
9. History of prostate cancer
10. History of kidney transplant
11. Cancer within the last five years, with the exception of non-metastatic skin cancers
12. Comorbid conditions requiring medication such as diabetes, kidney failure, liver failure, hepatitis, blood disorders, hypotension, thyroid disease, respiratory disorders, or cardiovascular disease
13. Presence of sleep apnea, moderate to severe restless leg syndrome, major circadian rhythm changes, or narcolepsy
14. Significant disease of the Central Nervous System (CNS) such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke
15. Diagnosis of major depression, schizophrenia, bipolar disorder, or other major psychiatric disorder as defined by DSM-V criteria
16. Diseases associated with dementia such as Alzheimer's disease, vascular dementia, normal pressure hydrocephalus or Parkinson's disease

Primary outcomes:
measure: Plasma concentration of withanolides after Shoden administration
timeFrame: 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)
Secondary outcomes:
measure: Time of maximum concentration of withanolides after Shoden administration
timeFrame: 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)
measure: Half-life of withanolides after Shoden administration
timeFrame: 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)
measure: Steady-state concentration of selected withanolides in plasma
timeFrame: For each study period, steady state concentration will be collected during week 4 following four weeks' daily use of Shoden.
measure: Urine concentration of withanolides after Shoden administration
timeFrame: For each study period, over 12 hours post-Shoden administration, 24-hour sample, 48-hour sample, four-week sample
measure: Adverse events
timeFrame: 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.
measure: Number of participants with abnormal ECG readings
timeFrame: For each study period, electrocardiography will be assessed at 0 and 420 minutes post-Shoden administration and at the four week follow-up visit
measure: Liver function
timeFrame: 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
measure: Kidney function
timeFrame: 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
measure: Thyroid-stimulating hormone
timeFrame: For each study period, thyroid-stimulating hormone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: Testosterone
timeFrame: For each study period, testosterone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: White blood cell count
timeFrame: For each study period, white blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: Red blood cell count
timeFrame: For each study period, red blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: Hemoglobin
timeFrame: For each study period, hemoglobin will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: Hematocrit
timeFrame: For each study period, hematocrit will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration.
measure: Feasibility of administering REDCap surveys
timeFrame: For each study period, prior to the pharmacokinetics visit and prior to the four-week follow-up visit
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Alex Speers, ND
role: PRINCIPAL_INVESTIGATOR
References: