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Effects of Garlic Supplements on Opioids in Healthy Volunteers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00499460
First Posted: July 11, 2007
Last Update Posted: April 7, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Danny Shen, Fred Hutchinson Cancer Research Center
  Purpose

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.


Condition Intervention Phase
Healthy, No Evidence of Disease Dietary Supplement: garlic powder tablets Drug: oxycodone Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Modulation of Opioid Effects by Garlic Supplements

Resource links provided by NLM:


Further study details as provided by Danny Shen, Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
    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.

  • Somatic Side Effects Total Score [ Time Frame: SSE scores at 150 min after a single 15-mg oral dose of oxycodone ]
    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.

  • Cognitive-Affective Side Effects Total Score [ Time Frame: CASE scores at 150 min after a single 15-mg oral dose of oxycodone ]
    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.

  • Oral Midazolam Test [ Time Frame: Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam ]
    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.

  • Oral Digoxin Test [ Time Frame: Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin ]
    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.


Enrollment: 15
Study Start Date: November 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I
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.
Dietary Supplement: garlic powder tablets
Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet
Other Name: Nature's Way Garlicin
Drug: oxycodone
Single administration of three 5-mg oxycodone tablets or a 15-mg dose
Other Name: oxycodone hydrochoride, Roxicodone
Arm II
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.
Dietary Supplement: garlic powder tablets
Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet
Other Name: Nature's Way Garlicin
Drug: oxycodone
Single administration of three 5-mg oxycodone tablets or a 15-mg dose
Other Name: oxycodone hydrochoride, Roxicodone

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA:

  • Healthy volunteer
  • Body mass index 20-32

EXCLUSION CRITERIA:

  • 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
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00499460


Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Danny D Shen, PhD Fred Hutchinson Cancer Research Center
  More Information

Responsible Party: Danny Shen, Principal Investigator, 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
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Danny Shen, Fred Hutchinson Cancer Research Center:
Healthy, No Evidence of Disease

Additional relevant MeSH terms:
Oxycodone
Diallyl disulfide
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antihypertensive Agents
Antineoplastic Agents
Spermatocidal Agents
Antispermatogenic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Antimutagenic Agents
Protective Agents
Anticarcinogenic Agents
Contraceptive Agents, Male