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| ID | Type | Description | Link |
|---|---|---|---|
| KL2TR002370 | U.S. NIH Grant/Contract | View source |
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Amended study protocol was not reapproved in time for completion of study activities.
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| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
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This study will measure the oral bioavailability and pharmacokinetics of known compounds from a standardized Withania somnifera botanical dietary supplement in healthy older adults.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Shoden 240 mg | Experimental | 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. |
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| Shoden 480 mg | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Withanolides After Shoden Administration | 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. | 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 | Description | Time Frame |
|---|---|---|
| Time of Maximum Concentration of Withanolides After Shoden Administration | The time of maximum (tmax) of withanolides over the first 48 hours post-Shoden administration will be calculated using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS). | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alex Speers, ND | Oregon Health and Science University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
The individual coded participant data that support the published results will be available to be shared for research purposes. Data, plasma, and urine specimens will be stored for future research in a repository. All data/specimens will be coded with each participant's identification code, visit number, and date of collection. Data will be available four months after publication ending five years post article publication.
For repository requests, the repository guardian Alex Speers (speers@ohsu.edu) or designee will review the requestor's institutional review board approval memo, protocol, and repository sharing agreement before samples/data are released. Separate institutional review board approval/determination will be required for each specific human subject research activity that uses coded data/specimens from the repository.
Data will be available four months after publication, ending five years post-publication.
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.
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Participants were recruited from April 2024 until September 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Shoden 240 mg First, Then Shoden 480 mg | At pharmacokinetics visit 1, participants receive a single dose of 240 mg Shoden, administered as two 120 mg capsules. Forty-eight hours later, participants receive a 35-day supply of Shoden, administered at 240 mg per day. After a 2- to 4-week washout period, participants attend pharmacokinetics visit 2, during which participants receive a single dose of 480 mg Shoden, administered as two 240 mg capsules. Forty-eight hours later, participants receive a 35-day supply of Shoden, administered at 480 mg per day. Shoden: 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. |
| FG001 | Shoden 480 mg First, Then Shoden 240 mg | At pharmacokinetics visit 1, participants receive a single dose of 480 mg Shoden, administered as two 240 mg capsules. Forty-eight hours later, participants receive a 35-day supply of Shoden, administered at 480 mg per day. After a 2- to 4-week washout period, participants attend pharmacokinetics visit 2, during which participants receive a single dose of 240 mg Shoden, administered as two 120 mg capsules. Forty-eight hours later, participants receive a 35-day supply of Shoden, administered at 240 mg per day. Shoden: 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Total number of participants enrolled and randomized to a sequence group.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants were randomized to receive either 240 mg Shoden first, then 480 mg Shoden, or 480 mg Shoden first, then 240 mg Shoden. Because all study participants were randomized to receive all interventions, baseline measures are presented for all study participants. Shoden: 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) of Withanolides After Shoden Administration | 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. | Sufficient blood samples to construct pharmacokinetic curves were only collected for two participants administered 240 mg Shoden and three participants administered 480 mg Shoden. Reasons for not collecting sufficient blood samples for all participants included inability to place intravenous catheter (n=1), mild anemia on 0-hour labs pre-Shoden administration (n=3), and gastrointestinal side effects during the visit (n=1). | Posted | Mean | Standard Deviation | ng/ml | 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) |
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For each study period (240 or 480 mg Shoden), an adverse events questionnaire was administered at baseline, 12 hours, 48 hours, 2 weeks, and 4 weeks. An adverse events questionnaire was also administered at the exit phone call, which was conducted two weeks after the final clinic visit (final clinic visit occurred up to 12 weeks post baseline of first study period).
Adverse events are reported by dose (240 or 480 mg Shoden) and are reported for all participants who were administered at least one dose of the intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Shoden 240 mg | Participants who received at least one dose of 240 mg Shoden. Shoden: 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Decreased appetite | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Alex Speers | Oregon Health & Science University | 5034185896 | speers@ohsu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 10, 2024 | Dec 15, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 13, 2024 | Feb 17, 2026 | ICF_001.pdf |
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| Half-life of Withanolides After Shoden Administration | The half-life (t1/2) of withanolides will be calculated using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS). | 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 | Concentration (ng/ml) of selected withanolides in plasma after four weeks' use | 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 | The concentration (ng/ml) of withanolides in urine will be measured in a pooled urine sample over 12 hours post-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) | Resting electrocardiography will be measured using a ten-lead electrocardiogram at the zero-minutes timepoint and 7 hours post-Shoden administration. Electrocardiogram changes will be assessed and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The number of participants with abnormal ECG readings at 7 hours compared to baseline will be reported. | 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) | Resting electrocardiography will be measured using a ten-lead electrocardiogram at the zero-minutes timepoint and 4-weeks post-Shoden administration. Electrocardiogram changes will be assessed and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The number of participants with abnormal ECG readings at 4 weeks compared to baseline will be reported. | For each study period, electrocardiography will be assessed at 0 and 4 weeks post-Shoden administration. |
| Mean Change in ALT (10 Hours) | A comprehensive metabolic panel will measure alanine aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | A comprehensive metabolic panel will measure alanine aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration. |
| Mean Change in AST (10 Hours) | A comprehensive metabolic panel will measure aspartate aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | A comprehensive metabolic panel will measure aspartate aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration. |
| Mean Change in Creatinine (10 Hours) | A comprehensive metabolic panel will measure creatinine as a marker of kidney function. Each parameter falling outside the normal range (0.5 to 1.2 milligrams per deciliter) will be compared to baseline values. If elevations are observed, alternative clinical explanations will be considered to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to 10-hours post-Shoden administration for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | A comprehensive metabolic panel will measure creatinine as a marker of kidney function. Each parameter falling outside the normal range (0.5 to 1.2 milligrams per deciliter) will be compared to baseline values. If elevations are observed, alternative clinical explanations will be considered to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | Thyroid-stimulating hormone will be measured in units of milli-international units per liter as a marker of thyroid function. Any changes in hormone levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hormone levels are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | Testosterone will be measured in units of nanograms per deciliter. Any changes in hormone levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in testosterone levels are attributable to the study intervention. Changes in testosterone will be analyzed by sex, by dose. | 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) | White blood cells will be measured in units of cells per cubic millimeter. Any changes in red blood cell levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in red blood cells are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | Red blood cells will be measured in units of cells per cubic millimeter. Any changes in red blood cell levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in red blood cells are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | Hemoglobin will be measured in grams per deciliter. Any changes in hemoglobin will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hemoglobin are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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) | Hematocrit will be measured in percent. Any changes in hematocrit will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hematocrit are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | 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 | The feasibility of administering REDCap surveys will be assessed by calculating the percentage of administered questionnaires that are returned and fully completed by participants, with feasibility defined as at least 80% of all administered questionnaires returned and completed. | For each study period, prior to the pharmacokinetics visit and prior to the four-week follow-up visit |
| Mild anemia noted on baseline labs at pharmacokinetics visit 2 |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Oral Temperature | Mean | Standard Deviation | degrees Farenheit |
|
| OG000 |
| 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. Blood will be collected at 17 timepoints over 48 hours. Shoden: 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. |
| OG001 | 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. Blood will be collected at 17 timepoints over 48 hours. Shoden: 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. |
|
|
| Secondary | Time of Maximum Concentration of Withanolides After Shoden Administration | The time of maximum (tmax) of withanolides over the first 48 hours post-Shoden administration will be calculated using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS). | Sufficient blood samples to construct pharmacokinetic curves were only collected for two participants administered 240 mg Shoden and three participants administered 480 mg Shoden. Reasons for not collecting sufficient blood samples for all participants included inability to place intravenous catheter (n=1), mild anemia on 0-hour labs pre-Shoden administration (n=3), and gastrointestinal side effects during the visit (n=1). | Posted | Mean | Standard Deviation | hours | 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 | Half-life of Withanolides After Shoden Administration | The half-life (t1/2) of withanolides will be calculated using liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS). | Posted | Mean | Standard Deviation | hours | 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) |
|
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| Secondary | Steady-state Concentration of Selected Withanolides in Plasma | Concentration (ng/ml) of selected withanolides in plasma after four weeks' use | The 4-week study period where participants were administered 480 mg Shoden every day was completed by only 3/5 participants who started that period. Two participants experienced gastrointestinal side effects and stopped taking the intervention within the first two weeks. Therefore, steady-state samples at four weeks were not collected for those participants. | Posted | Mean | Standard Deviation | ng/ml | For each study period, steady state concentration will be collected during week 4 following four weeks' daily use of Shoden. |
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| Secondary | Urine Concentration of Withanolides After Shoden Administration | The concentration (ng/ml) of withanolides in urine will be measured in a pooled urine sample over 12 hours post-Shoden administration. | Posted | Mean | Standard Deviation | micrograms excreted in 12 hours | For each study period, urine collected over the first 12 hours post-Shoden administration. |
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| Secondary | Number of Participants With Abnormal ECG Readings (7 Hours) | Resting electrocardiography will be measured using a ten-lead electrocardiogram at the zero-minutes timepoint and 7 hours post-Shoden administration. Electrocardiogram changes will be assessed and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The number of participants with abnormal ECG readings at 7 hours compared to baseline will be reported. | Posted | Count of Participants | Participants | 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. |
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| Secondary | Number of Participants With Abnormal ECG Readings (4 Weeks) | Resting electrocardiography will be measured using a ten-lead electrocardiogram at the zero-minutes timepoint and 4-weeks post-Shoden administration. Electrocardiogram changes will be assessed and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The number of participants with abnormal ECG readings at 4 weeks compared to baseline will be reported. | Posted | Count of Participants | Participants | For each study period, electrocardiography will be assessed at 0 and 4 weeks post-Shoden administration. |
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| Secondary | Mean Change in ALT (10 Hours) | A comprehensive metabolic panel will measure alanine aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | U/L | 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. |
|
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| Secondary | Mean Change in ALT (4 Weeks) | A comprehensive metabolic panel will measure alanine aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | U/L | For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration. |
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| Secondary | Mean Change in AST (10 Hours) | A comprehensive metabolic panel will measure aspartate aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | U/L | 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. |
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|
|
| Secondary | Mean Change in AST (4 Weeks) | A comprehensive metabolic panel will measure aspartate aminotransferase and in units per liter as a marker of liver function. Enzyme levels falling outside the normal range will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | U/L | For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration. |
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| Secondary | Mean Change in Creatinine (10 Hours) | A comprehensive metabolic panel will measure creatinine as a marker of kidney function. Each parameter falling outside the normal range (0.5 to 1.2 milligrams per deciliter) will be compared to baseline values. If elevations are observed, alternative clinical explanations will be considered to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to 10-hours post-Shoden administration for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | mg/dL | 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. |
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| Secondary | Mean Change in Creatinine (4 Weeks) | A comprehensive metabolic panel will measure creatinine as a marker of kidney function. Each parameter falling outside the normal range (0.5 to 1.2 milligrams per deciliter) will be compared to baseline values. If elevations are observed, alternative clinical explanations will be considered to determine if elevations are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | mg/dL | For each study period, liver function will be assessed at 0 and 4 weeks post-Shoden administration. |
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| Secondary | Mean Change in Thyroid-stimulating Hormone (4 Weeks) | Thyroid-stimulating hormone will be measured in units of milli-international units per liter as a marker of thyroid function. Any changes in hormone levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hormone levels are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | mIU/L | For each study period, thyroid-stimulating hormone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Mean Change in Testosterone (4 Weeks) | Testosterone will be measured in units of nanograms per deciliter. Any changes in hormone levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in testosterone levels are attributable to the study intervention. Changes in testosterone will be analyzed by sex, by dose. | Data is presented only for participants who completed at least one full study period for one of the two intervention doses. | Posted | Mean | Standard Deviation | ng/dL | For each study period, testosterone will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Mean White Blood Cell Count (4 Weeks) | White blood cells will be measured in units of cells per cubic millimeter. Any changes in red blood cell levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in red blood cells are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | 10^3 cells/microliter | For each study period, white blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Mean Change in Red Blood Cell Count (4 Weeks) | Red blood cells will be measured in units of cells per cubic millimeter. Any changes in red blood cell levels will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in red blood cells are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | 10^6 cells/µL | For each study period, red blood cells will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Mean Change in Hemoglobin (4 Weeks) | Hemoglobin will be measured in grams per deciliter. Any changes in hemoglobin will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hemoglobin are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | g/dL | For each study period, hemoglobin will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Mean Change in Hematocrit (4 Weeks) | Hematocrit will be measured in percent. Any changes in hematocrit will be compared to baseline levels. Alternative clinical explanations will be considered in order to determine if any changes in hematocrit are attributable to the study intervention. Changes in laboratory outcomes from the baseline visit to the four-week follow-up visit for each study period will be presented using descriptive statistics (e.g., means and standard deviations, frequency and percent). | Posted | Mean | Standard Deviation | percentage of total blood volume | For each study period, hematocrit will be assessed at 0 minutes post-Shoden administration and four weeks post-Shoden administration. |
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| Secondary | Percentage of REDCap Surveys Completed | The feasibility of administering REDCap surveys will be assessed by calculating the percentage of administered questionnaires that are returned and fully completed by participants, with feasibility defined as at least 80% of all administered questionnaires returned and completed. | Posted | Number | percentage of questionnaires completed | For each study period, prior to the pharmacokinetics visit and prior to the four-week follow-up visit |
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| 0 |
| 5 |
| 0 |
| 5 |
| 5 |
| 5 |
| EG001 | Shoden 480 mg | Participants who received at least one dose of 480 mg Shoden. Shoden: 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. | 0 | 6 | 0 | 6 | 6 | 6 |
| Indigestion | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Muscle aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Hypotension | Cardiac disorders | Systematic Assessment |
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| Allergy symptoms | Immune system disorders | Systematic Assessment |
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| Abdominal cramps | Gastrointestinal disorders | Systematic Assessment |
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| Vision changes | Eye disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Anxiety | Nervous system disorders | Systematic Assessment |
|
| Depression | General disorders | Systematic Assessment |
|
| Restlessness | General disorders | Systematic Assessment |
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| Irritability | General disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Chest pain | Cardiac disorders | Systematic Assessment |
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| Hypertension | Cardiac disorders | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Weight loss | General disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Muscoluskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hot flashes | General disorders | Systematic Assessment |
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| Insomnia | General disorders | Systematic Assessment |
|
Not provided
Not provided
| Sominone |
|
| Isomer of 2,3-Didehydrosomnifericin |
|
| Sominone |
|
| Isomer of 2,3-didehydrosomnifericin |
|
| Sominone |
|
| Isomer of 2,3-Didehydrosomnifericin |
|
| Isomer of 4-oxo-withaferin A as Phase II conjugates |
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| Sominone as Phase II conjugates |
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| Free isomer of 2,3-didehydrosomnifericin |
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