Healthy, No Evidence of DiseasePhase 4NCT00499460
Effects of Garlic Supplements on Opioids in Healthy Volunteers
A Phase 4 study testing garlic powder tablets and oxycodone in people with Healthy, No Evidence of Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, No Evidence of Disease
- What is being tested?
- garlic powder tablets and oxycodone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Aug 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteer
- Body mass index 20-32
Who cannot join
- Not pregnant
- No history of cardiopulmonary, liver, renal, endocrine, neurologic, or psychiatric disease
- No anemia
- No known adverse reactions to opioids, benzodiazepines, cardiac glycosides, or garlic supplements
- No known allergy or hypersensitivity to sulfur-containing food or drugs
- No significant gastrointestinal intolerance to lactose in dairy products
Show all 20Show fewer
- No recent history of alcohol or substance abuse
- No history of or concurrent heavy daily consumption of allium vegetables (i.e., garlic, shallots, leeks, and chives)
- No handicaps due to visual and hearing impairments
- No resting heart rate < 50 beats per minutes
- No abnormal cardiac rhythm by EKG
- No unusually sensitive response or resistance to pain stimulation (Cold Pressor Test)
- Must be right handed
- No color blindness
- No history of learning disabilities or dyslexia
- Must be literate and proficient in English
- Must be a nonsmoker
- No concurrent medication except oral contraceptives
- No concurrent grapefruit or grapefruit juice
- No other concurrent over-the-counter herbal products or herbal tea
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
About this study
Official title: Modulation of Opioid Effects by Garlic Supplements
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.
Read the detailed description
OBJECTIVES:
- To determine whether CYP3A (Cytochrome P450 3A) and/or P-glycoprotein mediated interactions exist between garlic supplements and oxycodone (a commonly used oral opioid analgesic) in healthy volunteers.
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.
- Arm I: In Period 1, participants receive oral garlic powder twice daily on days 1-28 and oral oxycodone on day 28. In Period 2, participants receive oral placebo twice daily on days 1-28 and oral oxycodone on day 28.
- Arm II: In Period 1, participants receive oral placebo twice daily on days 1-28 and oral oxycodone on days 28. In Period 2, participants receive oral garlic powder twice daily on days 1-28 and oral oxycodone on day 28.
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.
- Conditions
- Healthy, No Evidence of Disease
- Being tested
- garlic powder tablets, oxycodone
- Keywords
- Healthy, No Evidence of Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
garlic powder tabletsDietary supplement
Also called Nature's Way Garlicin
Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet
oxycodoneDrug
Also called oxycodone hydrochoride, Roxicodone
Single administration of three 5-mg oxycodone tablets or a 15-mg dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: garlic powder tablets; Drug: oxycodone |
| 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. Receives: Dietary Supplement: garlic powder tablets; Drug: oxycodone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startNov 2006
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy, No Evidence of DiseaseStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Danny Shen, Fred Hutchinson Cancer Center
- Investigators
- Danny D Shen, PhD, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499460
- Sponsor's protocol ID
- 2040.00
- Other IDs
- IR-6130, CDR0000551927, R21CA118334
- Status last verified
- Apr 2017
- First submitted
- 10 Jul 2007
- Last updated
- 7 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Opioid Effects by Garlic Supplements
- ClinicalTrials.gov ID
- NCT00499460
- Acronym / sponsor ID
- 2040.00
- Conditions
- Healthy, No Evidence of Disease
- Keywords
- Healthy, No Evidence of Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 7 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- To determine whether CYP3A (Cytochrome P450 3A) and/or P-glycoprotein mediated interactions exist between garlic supplements and oxycodone (a commonly used oral opioid analgesic) in healthy volunteers.
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.
- Arm I: In Period 1, participants receive oral garlic powder twice daily on days 1-28 and oral oxycodone on day 28. In Period 2, participants receive oral placebo twice daily on days 1-28 and oral oxycodone on day 28.
- Arm II: In Period 1, participants receive oral placebo twice daily on days 1-28 and oral oxycodone on days 28. In Period 2, participants receive oral garlic powder twice daily on days 1-28 and oral oxycodone on day 28.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Other | Dietary Supplement: garlic powder tablets, Drug: oxycodoneTwo 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. |
| Arm II | Other | Dietary Supplement: garlic powder tablets, Drug: oxycodoneTwo 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. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy volunteer
- Body mass index 20-32
Key exclusion criteria (20 listed)
- Not pregnant
- No history of cardiopulmonary, liver, renal, endocrine, neurologic, or psychiatric disease
- No anemia
- No known adverse reactions to opioids, benzodiazepines, cardiac glycosides, or garlic supplements
- No known allergy or hypersensitivity to sulfur-containing food or drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| garlic powder tabletsAlso: Nature's Way GarlicinEach Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet | Dietary supplement | Arm I, Arm II |
| oxycodoneAlso: oxycodone hydrochoride, RoxicodoneSingle administration of three 5-mg oxycodone tablets or a 15-mg dose | Drug | Arm I, Arm II |
Primary outcome
Oxycodone Oral Clearance
Time frame: Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone
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.
5 secondary outcomes
Cold Pressor Tolerance AUC
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
Somatic Side Effects Total Score
Time frame: SSE scores at 150 min after a single 15-mg oral dose of oxycodone
Cognitive-Affective Side Effects Total Score
Time frame: CASE scores at 150 min after a single 15-mg oral dose of oxycodone
Oral Midazolam Test
Time frame: Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam
Oral Digoxin Test
Time frame: Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Danny D Shen, PhD principal investigator
Fred Hutchinson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing garlic powder tablets and oxycodone in people with Healthy, No Evidence of Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxycodone Oral Clearance (time frame: Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2017.