Effect of Garlic Supplements on Opioids in Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00499460
First received: July 10, 2007
Last updated: April 30, 2012
Last verified: April 2012
  Purpose

RATIONALE: Garlic supplements may change the effectiveness of oxycodone used to relieve moderate or severe pain.

PURPOSE: This randomized phase I trial is studying how garlic supplements may change the effectiveness of opioids in healthy volunteers.


Condition Intervention Phase
Healthy, no Evidence of Disease
Dietary Supplement: garlic
Drug: digoxin
Drug: midazolam hydrochloride
Drug: oxycodone hydrochloride
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Modulation of Opioid Effects by Garlic Supplements

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Oxycodone hydrochloride pharmacodynamic measures

Secondary Outcome Measures:
  • Oxycodone hydrochloride pharmacokinetic parameters

Enrollment: 18
Study Start Date: November 2006
Study Completion Date: September 2008
Arms Assigned Interventions
Active Comparator: Garlic
Arm I: Participants receive oral garlic twice daily on days 1-28 and oral oxycodone hydrochloride on days 2 and 28. Participants then receive oral placebo twice daily on days 58-87 and oral oxycodone hydrochloride on days 60 and 85.
Dietary Supplement: garlic Drug: digoxin Drug: midazolam hydrochloride Drug: oxycodone hydrochloride Genetic: gene expression analysis Genetic: protein expression analysis Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: pharmacological study
Placebo Comparator: Placebo
Arm II: Participants receive oral placebo twice daily on days 1-28 and oral oxycodone hydrochloride on days 2 and 28. Participants then receive oral garlic twice daily on days 58-87 and oral oxycodone hydrochloride on days 60-85.
Drug: digoxin Drug: midazolam hydrochloride Drug: oxycodone hydrochloride Genetic: gene expression analysis Genetic: protein expression analysis Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: pharmacological study

Detailed Description:

OBJECTIVES:

  • Determine whether a CYP3A- and P-glycoprotein-dependent interaction exists between garlic supplements and a commonly used oral opioid analgesic (oxycodone hydrochloride) in healthy volunteers.

OUTLINE: This is a single-blind, randomized, crossover study. Participants are randomized to 1 of 2 arms.

  • Arm I: Participants receive oral garlic twice daily on days 1-28 and oral oxycodone hydrochloride on days 2 and 28. Participants then receive oral placebo twice daily on days 58-87 and oral oxycodone hydrochloride on days 60 and 85.
  • Arm II: Participants receive oral placebo twice daily on days 1-28 and oral oxycodone hydrochloride on days 2 and 28. Participants then receive oral garlic twice daily on days 58-87 and oral oxycodone hydrochloride on days 60-85.

In both arms, participants receive oral midazolam hydrochloride and oral digoxin once on days 29 and 86. Blood samples are collected periodically and examined by liquid chromatography-mass spectrometry (LC-MS) for CYP3A4 and P-glycoprotein phenotyping.

Blood and urine samples are collected after receiving oxycodone hydrochloride for pharmacokinetic-pharmacodynamic studies via LC-MS.

Pain response is assessed at baseline and periodically after oxycodone hydrochloride treatment via electrical stimulation and the cold pressor test. Side effects of oxycodone hydrochloride treatment are assessed via questionnaires and tests for cognitive function, manipulative dexterity, motor speed, and visual attention.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

DISEASE CHARACTERISTICS:

  • Healthy volunteer
  • Body mass index 20-32

PATIENT CHARACTERISTICS:

  • 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 (cutaneous electrical stimulation and 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

PRIOR CONCURRENT THERAPY:

  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499460

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

Additional Information:
No publications provided

Responsible Party: Danny Shen, MD, FHCRC
ClinicalTrials.gov Identifier: NCT00499460     History of Changes
Other Study ID Numbers: 2040.00, IR-6130, CDR0000551927
Study First Received: July 10, 2007
Last Updated: April 30, 2012
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
healthy, no evidence of disease

Additional relevant MeSH terms:
Digoxin
Midazolam
Oxycodone
Analgesics, Opioid
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Adjuvants, Anesthesia
Central Nervous System Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014