Official Title: “Modulation of Opioid Effects by Garlic Supplements”

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.

Study Type: Observational

Study Design: N/A

Study Primary Completion Date: April 2008

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.

Intervention(s) in this Clinical Trial

• Drug: digoxin
• Drug: garlic
• Drug: midazolam hydrochloride
• Drug: oxycodone hydrochloride
• Procedure: gene expression analysis
• Procedure: laboratory biomarker analysis
• Procedure: liquid chromatography
• Procedure: mass spectrometry
• Procedure: pharmacological study
• Procedure: protein expression analysis

Primary Measures

• Oxycodone hydrochloride pharmacodynamic measures

Secondary Measures

• Oxycodone hydrochloride pharmacokinetic parameters

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Fred Hutchinson Cancer Research Center

Overall Clinical Trial Officials and Contacts

Danny Shen, PhD Principal Investigator Fred Hutchinson Cancer Research Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00499460

Study ID Number: CDR0000551927

ClinicalTrials.gov Identifier: NCT00499460

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database