Effects of Garlic Supplements on Opioids in Healthy Volunteers

NCT ID: NCT00499460

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2008-08-31

Brief 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 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.

Conditions

Healthy, No Evidence of Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: OTHER

garlic powder tablets

Intervention Type: DIETARY_SUPPLEMENT

Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet

oxycodone

Intervention Type: DRUG

Single administration of three 5-mg oxycodone tablets or a 15-mg dose

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.

Group Type: OTHER

garlic powder tablets

Intervention Type: DIETARY_SUPPLEMENT

Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet

oxycodone

Intervention Type: DRUG

Single administration of three 5-mg oxycodone tablets or a 15-mg dose

Interventions

garlic powder tablets

Each Garlicin tablet has a claimed allicin content of 3,200 microgram per tablet

Intervention Type: DIETARY_SUPPLEMENT

oxycodone

Single administration of three 5-mg oxycodone tablets or a 15-mg dose

Intervention Type: DRUG

Other Intervention Names

Nature's Way Garlicin; oxycodone hydrochoride, Roxicodone

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Danny Shen

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Danny D Shen, PhD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

IR-6130

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000551927

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA118334

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2040.00

Identifier Type: -

Identifier Source: org_study_id