Trial Outcomes & Findings for Effects of Garlic Supplements on Opioids in Healthy Volunteers (NCT NCT00499460)
NCT ID: NCT00499460
Last Updated: 2017-04-07
Results Overview
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.
COMPLETED
PHASE4
15 participants
Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone
2017-04-07
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Intervention 1 (30 Days)
STARTED
|
8
|
7
|
|
Intervention 1 (30 Days)
COMPLETED
|
6
|
7
|
|
Intervention 1 (30 Days)
NOT COMPLETED
|
2
|
0
|
|
Intervention 2 (30 Days)
STARTED
|
6
|
7
|
|
Intervention 2 (30 Days)
COMPLETED
|
6
|
6
|
|
Intervention 2 (30 Days)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Intervention 1 (30 Days)
Withdrawal by Subject
|
1
|
0
|
|
Intervention 1 (30 Days)
Fainting upon Blood Draw
|
1
|
0
|
|
Intervention 2 (30 Days)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Effects of Garlic Supplements on Opioids in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Garlic First, Then Placebo
n=6 Participants
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.
|
Placebo First, Then Garlic
n=6 Participants
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
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
28.3 years
STANDARD_DEVIATION 5.2 • n=5 Participants
|
30.5 years
STANDARD_DEVIATION 6.0 • n=7 Participants
|
29.9 years
STANDARD_DEVIATION 5.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodoneOxycodone 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Oxycodone Oral Clearance
|
1.82 L/min
Standard Deviation 0.40
|
2.04 L/min
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: 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 oxycodoneCold 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Cold Pressor Tolerance AUC
|
3.513 log (sec*min)
Standard Deviation 0.904
|
3.715 log (sec*min)
Standard Deviation 0.604
|
SECONDARY outcome
Timeframe: SSE scores at 150 min after a single 15-mg oral dose of oxycodoneSubjects 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Somatic Side Effects Total Score
|
0.560 units on a scale
Standard Deviation 0.140
|
0.711 units on a scale
Standard Deviation 0.184
|
SECONDARY outcome
Timeframe: CASE scores at 150 min after a single 15-mg oral dose of oxycodoneSubjects 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Cognitive-Affective Side Effects Total Score
|
1.884 units on a scale
Standard Deviation 0.118
|
1.714 units on a scale
Standard Deviation 0.147
|
SECONDARY outcome
Timeframe: Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolamMidazolam 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Oral Midazolam Test
|
2491 (ng/mL)*min
Standard Deviation 789
|
2495 (ng/mL)*min
Standard Deviation 825
|
SECONDARY outcome
Timeframe: Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxinDigoxin 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.
Outcome measures
| Measure |
Garlic
n=12 Participants
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
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
Oral Digoxin Test
|
231 (ng/mL)*min
Standard Deviation 50
|
226 (ng/mL)*min
Standard Deviation 58
|
Adverse Events
Garlic
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Danny D. Shen, Member (Retired)
Clinical Research Division, Fred Hutchinson Cancer Research Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place