Effect of Garlic Supplements on Opioids in Healthy Volunteers - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00499460

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 IV

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:

MedlinePlus related topics: Cancer Dietary Supplements

Drug Information available for: Digoxin Midazolam Midazolam maleate Midazolam hydrochloride Oxycodone Oxycodone hydrochloride Allium sativum extract

U.S. FDA Resources

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

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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Danny Shen, PhD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	September 22, 2010
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
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs
Adjuvants, Anesthesia
Central Nervous System Agents

Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Hypnotics and Sedatives
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 February 13, 2012