Safety, Tolerability, and Pharmacokinetics of an Oral Withania Somnifera Product in Older Adults

NCT07008300 | Withdrawn Early Phase 1

• 2 other identifiers: STUDY00026055KL2TR002370
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Aging

Keywords

Withania; Herbal Medicine; Dietary Supplements

Outcome Measures

Primary Outcomes (1)

• Plasma concentration of withanolides after Shoden administration

  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)).

  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)

Secondary Outcomes (15)

• 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.

Study Arms (2)

Shoden 120 mg

EXPERIMENTAL

Shoden, administered as a single 120 mg capsule, once at the pharmacokinetics visit and once daily for four weeks following the 48 hour visit.

Dietary Supplement: Shoden

Shoden 240 mg

EXPERIMENTAL

Shoden, administered as a single 240 mg capsule, once at the pharmacokinetics visit and once daily for four weeks following the 48 hour visit.

Dietary Supplement: Shoden

Interventions

Shoden DIETARY_SUPPLEMENT

Shoden® powder is a commercial, dried 70% ethanolic extract of Withania somnifera (ashwagandha, WS) root and leaf, standardized to 35% withanolide glycosides. Shoden® powder is manufactured by Arjuna Natural Pvt Ltd, based in Kochi, Kerala, India.

Shoden 120 mg; Shoden 240 mg

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS): collaborator
• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Study Officials

• Alex Speers, ND

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 6, 2025
• Study Start: July 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be available four months after publication, ending five years post-publication.
• Access Criteria: For repository requests, the repository guardian will review the requestor's institutional review board approval memo, protocol, and repository sharing agreement before samples/data are released. The Guardian will check for genetic opt out status, withdrawn consent for data/samples, and limitations on future use of data/samples. A signed Repository Sharing Agreement will be collected before data or samples are released. The Repository Guardian will ensure that material transfer agreements for the transfer of biological materials and data use agreements for data shared outside of Oregon Health \& Science University are executed as applicable. Specimens and data will be coded with the participant's identification code, visit number, and date of collection. The key for requested specimens and data will be provided separately and with appropriate institutional review board approval.

Locations

US (1)