Clinical trial NCT00499460: Effects of Garlic Supplements on Opioids in Healthy Volunteers
Official title: Modulation of Opioid Effects by Garlic Supplements
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy, No Evidence of Disease
Keywords: Healthy, No Evidence of Disease
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-07-11
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Oxycodone Oral Clearance
timeFrame: Serial blood sampling over 24 hours after a 15-mg oral dose of oxycodone
Secondary outcomes:
measure: Cold Pressor Tolerance AUC
timeFrame: 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
measure: Somatic Side Effects Total Score
timeFrame: SSE scores at 150 min after a single 15-mg oral dose of oxycodone
measure: Cognitive-Affective Side Effects Total Score
timeFrame: CASE scores at 150 min after a single 15-mg oral dose of oxycodone
measure: Oral Midazolam Test
timeFrame: Serial blood sampling over 6 hours after a 5-mg oral test dose of midazolam
measure: Oral Digoxin Test
timeFrame: Serial blood sampling over 4 hours after a 0.5-mg oral test dose of digoxin
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Danny D Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References: