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| ID | Type | Description | Link |
|---|---|---|---|
| IR-6130 | Other Identifier | FHCRC IRB | |
| CDR0000551927 | Other Identifier | PDQ | |
| R21CA118334 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Garlic supplements may alter the pharmacokinetics of oxycodone, thereby affecting its effectiveness as an opioid analgesic for the relief of moderate or severe pain.
PURPOSE: This randomized phase 4 trial is studying how garlic supplements may change the pharmacokinetics of oxycodone and its analgesic and side effects in healthy volunteers.
OBJECTIVES:
OUTLINE:
This is a single-blind, randomized, crossover study. Participants are randomized to 1 of 2 arms. Each arm entails two 30-day treatment periods, with a washout of at least 4 weeks in between.
In both periods of each arm, participants receive a combination of oral midazolam and oral digoxin for CYP3A and P-glycoprotein phenotyping on day 29. Blood samples are collected periodically and analyzed by liquid chromatography-mass spectrometry (LC-MS).
Blood and urine samples are collected after receiving oxycodone for pharmacokinetic characterization. Plasma concentrations of oxycodone and its metabolites are measured by LC-MS.
Response to experimentally induced pain by the Cold Pressor Test (CPT) is assessed at baseline and periodically after oxycodone treatment. Subjective ratings of opioid side effects are assessed by validated questionnaires for somatic side effects and cognitive function impairments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Other | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral garlic powder tablet twice daily on days 1-30, oral oxycodone on day 28, and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral placebo twice daily on days 1-30, oral oxycodone on day 28, and a combination of oral midazolam and digoxin on day 29. |
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| Arm II | Other | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral placebo twice daily on days 1-30, oral oxycodone on day 28, and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral garlic powder tablet twice daily on days 1-30, oral oxycodone on day 28, and a combination of oral midazolam and digoxin on day 29. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| garlic powder tablets | Dietary Supplement | Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet |
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| Measure | Description | Time Frame |
|---|---|---|
| Oxycodone Oral Clearance | Oxycodone oral clearance is computed by Dose/AUC, where AUC is the area under the plasma oxycodone concentration-time curve from time zero to infinity. Oral clearance is a measure of the rate at which oxycodone is cleared from the body via metabolism. | Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone |
| Measure | Description | Time Frame |
|---|---|---|
| Cold Pressor Tolerance AUC | Cold Pressor Test measures response to experimentally induced pain, in this case by immersion of a subject's hand in icy-cold water. Tolerance is the duration of time a subject is able to keep his/her hand immersed in the cold water. A prolongation in tolerance time indicates analgesic response to oxycodone treatment. Cold Pressor Tolerance AUC is the area under the tolerance versus time curve over a 300-min period after a test dose of oxycodone. Because of non-normality in sample distribution, log transformed AUC estimates were analyzed by Generalized Linear Model. |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Danny D Shen, PhD | Fred Hutchinson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109-1024 | United States |
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Recruitment period was between November 2006 and August 2008. Healthy subjects were recruited from the University of Washington and Fred Hutchinson Cancer Research Center campuses through public notices.
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| ID | Title | Description |
|---|---|---|
| FG000 | Garlic First, Then Placebo | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral garlic powder (Nature's Way Garlicin tablet) twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral placebo tablet twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. |
| FG001 | Placebo First, Then Garlic | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral placebo tablet twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral garlic powder (Nature's Way Garlicin tablet) twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention 1 (30 Days) |
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| Intervention 2 (30 Days) |
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Of the 15 enrollees, 6 subjects completed the study protocol in each assigned arm; hence, baseline analysis is only available in those 12 subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | Garlic First, Then Placebo | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral garlic powder (Nature's Way Garlicin tablet) twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral placebo tablet twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. |
| 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 | Oxycodone Oral Clearance | Oxycodone oral clearance is computed by Dose/AUC, where AUC is the area under the plasma oxycodone concentration-time curve from time zero to infinity. Oral clearance is a measure of the rate at which oxycodone is cleared from the body via metabolism. | Posted | Mean | Standard Deviation | L/min | Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone |
|
Adverse event data were collected from all enrolled subjects over the 3-month duration of their study.
Adverse event collection relied on subject self-reporting during the 30-day garlic or placebo treatment. Subjects were monitored by pulse oximetry and observed for opioid side effects by trained nurses on the oxycodone test day. Blood pressure and heart rate were monitored on the oral digoxin and midazolam test day.
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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 | Garlic | Data for all subjects during their active garlic treatment period in both arms were pooled. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Danny D. Shen, Member (Retired) | Clinical Research Division, Fred Hutchinson Cancer Research Center | 206-685-2920 | ds@uw.edu |
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| ID | Term |
|---|---|
| D010098 | Oxycodone |
| ID | Term |
|---|---|
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
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| oxycodone | Drug | Single administration of three 5-mg oxycodone tablets or a 15-mg dose |
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| Repeated testing for tolerance to Cold Pressor Test just before and at 45, 90, 150 and 300 min after a single 15-mg oral dose of oxycodone |
| Somatic Side Effects Total Score | Subjects rated the bodily side effects they experienced at 90, 150 and 300 min after oxycodone administration on a 35-item Somatic Side Effects (SSE) questionnaire. Total score (i.e., average of the scores for all 35 items) ranges on a numerical scale from 0 (no somatic side effects) to a maximum of 4 (extreme somatic aide effects). Only the peak SSE scores at 150 min are reported herein. | SSE scores at 150 min after a single 15-mg oral dose of oxycodone |
| Cognitive-Affective Side Effects Total Score | Subjects rated the mental side effects they experienced at 90, 150 and 300 min after oxycodone administration on a 36-item Cognitive-Affective Side Effects (CASE) questionnaire. Total score (i.e., average of the scores for all 36 items) ranges on a numerical scale from 0 (no somatic side effects) to a maximum of 4 (extreme somatic aide effects). Only the peak CASE scores at 150 min are reported herein. | CASE scores at 150 min after a single 15-mg oral dose of oxycodone |
| Oral Midazolam Test | Midazolam when given orally is a probe substrate for the in vivo intestinal and hepatic activity of CYP3A (Cytochrome P450 3A) enzymes. The phenotype index in this case is the area under the plasma midazolam concentration from time zero to 360 min after a 5-mg oral test dose. A decrease in oral midazolam AUC indicates enhanced activity of CYP3A enzymes, possibly as a result of enzyme induction. | Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam |
| Oral Digoxin Test | Digoxin when given orally is a probe substrate for the efflux activity of P-glycoprotein in the small intestine. The phenotype index in this case is the area under the plasma digoxin concentration from time zero to 240 min after a 0.5-mg oral test dose. A decrease in oral digoxin AUC indicates an enhanced activity of P-glycoprotein, possibly as a result of transporter upregulation. | Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin |
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| BG001 | Placebo First, Then Garlic | Two 30-day treatment periods separated by a washout of at least 4 weeks. In Period 1, participants receive oral placebo tablet twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. In Period 2, participants receive oral garlic powder (Nature's Way Garlicin tablet) twice daily on days 1-30, and undergo testings with oxycodone on day 28 and a combination of oral midazolam and digoxin on day 29. |
| BG002 | Total | Total of all reporting groups |
| 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 |
|
| Region of Enrollment | Count of Participants | Participants |
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| Secondary | Cold Pressor Tolerance AUC | Cold Pressor Test measures response to experimentally induced pain, in this case by immersion of a subject's hand in icy-cold water. Tolerance is the duration of time a subject is able to keep his/her hand immersed in the cold water. A prolongation in tolerance time indicates analgesic response to oxycodone treatment. Cold Pressor Tolerance AUC is the area under the tolerance versus time curve over a 300-min period after a test dose of oxycodone. Because of non-normality in sample distribution, log transformed AUC estimates were analyzed by Generalized Linear Model. | Posted | Mean | Standard Deviation | log (sec*min) | Repeated testing for tolerance to Cold Pressor Test just before and at 45, 90, 150 and 300 min after a single 15-mg oral dose of oxycodone |
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|
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| Secondary | Somatic Side Effects Total Score | Subjects rated the bodily side effects they experienced at 90, 150 and 300 min after oxycodone administration on a 35-item Somatic Side Effects (SSE) questionnaire. Total score (i.e., average of the scores for all 35 items) ranges on a numerical scale from 0 (no somatic side effects) to a maximum of 4 (extreme somatic aide effects). Only the peak SSE scores at 150 min are reported herein. | Posted | Mean | Standard Deviation | units on a scale | SSE scores at 150 min after a single 15-mg oral dose of oxycodone |
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|
|
| Secondary | Cognitive-Affective Side Effects Total Score | Subjects rated the mental side effects they experienced at 90, 150 and 300 min after oxycodone administration on a 36-item Cognitive-Affective Side Effects (CASE) questionnaire. Total score (i.e., average of the scores for all 36 items) ranges on a numerical scale from 0 (no somatic side effects) to a maximum of 4 (extreme somatic aide effects). Only the peak CASE scores at 150 min are reported herein. | Posted | Mean | Standard Deviation | units on a scale | CASE scores at 150 min after a single 15-mg oral dose of oxycodone |
|
|
|
|
| Secondary | Oral Midazolam Test | Midazolam when given orally is a probe substrate for the in vivo intestinal and hepatic activity of CYP3A (Cytochrome P450 3A) enzymes. The phenotype index in this case is the area under the plasma midazolam concentration from time zero to 360 min after a 5-mg oral test dose. A decrease in oral midazolam AUC indicates enhanced activity of CYP3A enzymes, possibly as a result of enzyme induction. | Posted | Mean | Standard Deviation | (ng/mL)*min | Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam |
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| Secondary | Oral Digoxin Test | Digoxin when given orally is a probe substrate for the efflux activity of P-glycoprotein in the small intestine. The phenotype index in this case is the area under the plasma digoxin concentration from time zero to 240 min after a 0.5-mg oral test dose. A decrease in oral digoxin AUC indicates an enhanced activity of P-glycoprotein, possibly as a result of transporter upregulation. | Posted | Mean | Standard Deviation | (ng/mL)*min | Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin |
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| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Placebo | Data for all subjects during their placebo treatment period in both arms were pooled. | 0 | 15 | 0 | 15 | 0 | 15 |
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| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |