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Trial record 97 of 663 for:    OXYCODONE

Effects of Garlic Supplements on Opioids in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00499460
Recruitment Status : Completed
First Posted : July 11, 2007
Results First Posted : April 7, 2017
Last Update Posted : April 7, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Danny Shen, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Basic Science
Condition Healthy, No Evidence of Disease
Interventions Dietary Supplement: garlic powder tablets
Drug: oxycodone
Enrollment 15
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Garlic First, Then Placebo Placebo First, Then Garlic
Hide Arm/Group Description 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. 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.
Period Title: Intervention 1 (30 Days)
Started 8 7
Completed 6 7
Not Completed 2 0
Reason Not Completed
Withdrawal by Subject             1             0
Fainting upon Blood Draw             1             0
Period Title: Intervention 2 (30 Days)
Started 6 7
Completed 6 6
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title Garlic First, Then Placebo Placebo First, Then Garlic Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 6 6 12
Hide Baseline Analysis Population Description
Of the 15 enrollees, 6 subjects completed the study protocol in each assigned arm; hence, baseline analysis is only available in those 12 subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants
28.3  (5.2) 30.5  (6.0) 29.9  (5.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
3
  50.0%
3
  50.0%
6
  50.0%
Male
3
  50.0%
3
  50.0%
6
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Hispanic or Latino
1
  16.7%
0
   0.0%
1
   8.3%
Not Hispanic or Latino
5
  83.3%
6
 100.0%
11
  91.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  16.7%
1
   8.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
5
  83.3%
11
  91.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 12 participants
6
 100.0%
6
 100.0%
12
 100.0%
1.Primary Outcome
Title Oxycodone Oral Clearance
Hide Description 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.
Time Frame Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of oxycodone oral clearance following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of oxycodone oral clearance following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: L/min
1.82  (0.40) 2.04  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The primary hypothesis being tested is that garlic powder treatment increases metabolic clearance of oxycodone through enzyme induction and results in lower exposure to oxycodone.
Statistical Test of Hypothesis P-Value >0.05
Comments Significance probability for the treatment variable in the Generalized Linear Model
Method Generalized Estimating Equations
Comments Response variable is oxycodone oral clearance. Explanatory variables include treatment, period and gender, along with their interaction terms.
2.Secondary Outcome
Title Cold Pressor Tolerance AUC
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of Cold Pressor Test Tolerance AUC following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of Cold Pressor Test Tolerance AUC following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: log (sec*min)
3.513  (0.904) 3.715  (0.604)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The secondary hypothesis being tested is that powder garlic treatment lowers Cold Pressor Test tolerance (i.e., diminished analgesic response) after oxycodone administration due to a more rapid metabolic clearance and lower exposure to oxycodone.
Statistical Test of Hypothesis P-Value >0.05
Comments Significance probability for the treatment variable in the Generalized Linear Model
Method Generalized Estimating Equations
Comments Response variable is log Tolerance AUC. Explanatory variables include treatment, period and gender, along with their interaction terms.
3.Secondary Outcome
Title Somatic Side Effects Total Score
Hide Description 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.
Time Frame SSE scores at 150 min after a single 15-mg oral dose of oxycodone
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of SSE Total Score following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of SSE Total Score following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.560  (0.140) 0.711  (0.184)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The secondary hypothesis being tested is that garlic powder treatment lowers opioid side effects after oxycodone administration due to a more rapid metabolic clearance and lower exposure to oxycodone.
Statistical Test of Hypothesis P-Value >0.05
Comments Significance probability for the treatment variable in the Generalized Linear Model
Method Generalized Estimating Equations
Comments Response variable is total SSE rating score. Explanatory variables include treatment, period, time and gender, along with their interaction terms.
4.Secondary Outcome
Title Cognitive-Affective Side Effects Total Score
Hide Description 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.
Time Frame CASE scores at 150 min after a single 15-mg oral dose of oxycodone
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of CASE Total Score following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of CASE Total Score following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.884  (0.118) 1.714  (0.147)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The secondary hypothesis being tested is that garlic powder treatment lowers opioid side effects after oxycodone administration due to a more rapid metabolic clearance and lower exposure to oxycodone.
Statistical Test of Hypothesis P-Value >0.05
Comments Significance probability for the treatment variable in the Generalized Linear Model
Method Generalized Estimating Equations
Comments Response variable is total CASE rating score. Explanatory variables include treatment, period, time and gender, along with their interaction terms.
5.Secondary Outcome
Title Oral Midazolam Test
Hide Description 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.
Time Frame Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of oral midazolam AUC following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of oral midazolam AUC following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: (ng/mL)*min
2491  (789) 2495  (825)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments The secondary hypothesis being tested is that garlic powder induces CYP3A-mediated metabolism resulting in a lower oral midazolam AUC.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 1 sided
Comments Garlic powder versus placebo
6.Secondary Outcome
Title Oral Digoxin Test
Hide Description 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.
Time Frame Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Garlic Placebo
Hide Arm/Group Description:
Mean and standard deviation of oral digoxin AUC following garlic powder treatment were calculated by pooling data from the active treatment period in each assigned arm
Mean and standard deviation of oral digoxin AUC following placebo treatment were calculated by pooling data from the placebo treatment period in each assigned arm
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: (ng/mL)*min
231  (50) 226  (58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Garlic, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The secondary hypothesis being tested is that garlic powder treatment induces intestinal P-glycoprotein, reduces the bioavailability and hence AUC of orally administered digoxin.
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 1 sided
Comments Garlic powder versus placebo
Time Frame Adverse event data were collected from all enrolled subjects over the 3-month duration of their study.
Adverse Event Reporting Description 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.
 
Arm/Group Title Garlic Placebo
Hide Arm/Group Description Data for all subjects during their active garlic treatment period in both arms were pooled. Data for all subjects during their placebo treatment period in both arms were pooled.
All-Cause Mortality
Garlic Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/15 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Garlic Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/15 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Garlic Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/15 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Danny D. Shen, Member (Retired)
Organization: Clinical Research Division, Fred Hutchinson Cancer Research Center
Phone: 206-685-2920
EMail: ds@uw.edu
Layout table for additonal information
Responsible Party: Danny Shen, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00499460     History of Changes
Other Study ID Numbers: 2040.00
IR-6130 ( Other Identifier: FHCRC IRB )
CDR0000551927 ( Other Identifier: PDQ )
R21CA118334 ( U.S. NIH Grant/Contract )
First Submitted: July 10, 2007
First Posted: July 11, 2007
Results First Submitted: February 7, 2017
Results First Posted: April 7, 2017
Last Update Posted: April 7, 2017