Clinical trial NCT06693960: Evaluating the Pharmacokinetics of Oregano and Potential Oregano-drug Interactions Using a Drug Cocktail Approach
Official title: Evaluating the Pharmacokinetics of Oregano and Potential Oregano-drug Interactions Using a Drug Cocktail Approach
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Interaction
Keywords: pharmacokinetics
drug interaction
natural products
oregano
cytochrome P450
cocktail
Lead sponsor: Washington State University
Sponsor class: OTHER
Collaborators: name: Office of Dietary Supplements (ODS)
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2024-11-19
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this clinical trial is to determine how the supplement oregano affects how the body metabolizes pharmaceutical drugs.

Detailed description: Oregano (Origanum vulgare) is a flowering plant native to Europe. The fresh or dried leaves are commonly used as a cooking herb. Oregano oil extracts are also marketed as herbal supplements. O. vulgare ranked as the number 12 top-selling herbal supplement in the natural channel in 2022. Oregano supplements are consumed for myriad purported medicinal properties, including antimicrobial, antioxidant, and anti-inflammatory effects. Oregano contains multiple types of compounds, including phenols, terpenes, and terpenoids. Recent compelling in vitro data showed that an extract of O. vulgare activated the human pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR), which regulate the expression and activity of the prominent drug metabolizing enzymes cytochrome P450 (CYP) 3A4 and CYP1A2, respectively. PXR also regulates the expression and activity of several other CYPs (e.g., CYP2C9, CYP2C19), as well as transporters (e.g., the efflux transporter P-glycoprotein (P-gp)). The extent of activation of both receptors by O. vulgare rivaled that of St. John's wort, a well-known herbal supplement that induces CYP and P-gp activity in human participants. These investigators next evaluated the effects of O. vulgare on CYP3A4 and CYP1A2 activity in human hepatocytes. Again, the extent of induction by O. vulgare rivaled that of St. John's wort. Collectively, these observations suggest that oregano supplements could precipitate numerous interactions with pharmaceutical drugs.

The primary objective of the proposed study is to evaluate the potential for a well-characterized O. vulgare product to precipitate pharmacokinetic interactions with a "cocktail" of oral drugs that are substrates for multiple CYPs. The investigators and others have shown this validated cocktail (caffeine, dextromethorphan, losartan, midazolam, and omeprazole) to be safe to administer to healthy adult participants. The secondary objective is to determine the pharmacokinetics of the oregano supplement, which to date have not been rigorously characterized in humans. Results will be used to help inform healthcare practitioners and consumers about the safe use of this increasingly popular herbal supplement when consumed with certain pharmaceutical drugs.

Eligibility criteria: Inclusion Criteria:

* Between 18-64 years old and healthy
* Not taking any medications (prescription and non-prescription) or dietary/herbal supplements that can interfere with study drug pharmacokinetics
* Willing to abstain from consuming dietary/herbal supplements and citrus juices for several weeks
* Willing to abstain from cannabis/marijuana, hemp, and THC- and CBD-containing products for several weeks
* Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and the morning of the first day of each study arm
* Willing to abstain from consuming any alcoholic beverages for at least 1 day prior to any study day and during the study day
* Willing to use a secondary method of birth control that does not include the introduction or discontinuance of hormonal-based birth control (such as abstinence, copper IUD, or condoms). Specifically, regardless of the use hormonal-based birth control, a non-hormonal method should be used for the duration of the study and for three weeks following cessation of participation.
* Willing to abstain from consuming oregano (as a food additive or otherwise) for the duration of the study
* Geographically located within a 40-mile radius of Spokane and have the time to participate

Exclusion Criteria:

* Under 18 or over 64 years old
* Taking medications or dietary/herbal supplements that can interfere with study drug pharmacokinetics
* Have a major illness
* Taking medication/supplements for a mineral deficiency
* History of intolerance or allergy to oregano or any of the cocktail drugs (caffeine, dextromethorphan, losartan, midazolam, and omeprazole)
* Use of cannabis/marijuana, hemp, and CBD- and/or THC-containing products within the last month
* Currently using drugs or illicit substances for recreational purposes
* Pregnant or nursing
* Geographically located outside the 40-mile radius of Spokane and do not have the time to participate
* Cannot read and speak English

Primary outcomes:
measure: Midazolam Area under the plasma concentration vs. time curve (AUC) ratio
timeFrame: 0-24 hours
Secondary outcomes:
measure: Caffeine AUC ratio
timeFrame: 0-24 hours
measure: Caffeine maximum plasma concentration (Cmax) ratio
timeFrame: 0-24 hours
measure: Caffeine half-life ratio
timeFrame: 0-24 hours
measure: Dextromethorphan AUC ratio
timeFrame: 0-24 hours
measure: Dextromethorphan Cmax ratio
timeFrame: 0-24 hours
measure: Dextromethorphan half-life ratio
timeFrame: 0-24 hours
measure: Losartan AUC ratio
timeFrame: 0-24 hours
measure: Losartan Cmax ratio
timeFrame: 0-24 hours
measure: Losartan half-life ratio
timeFrame: 0-24 hours
measure: Midazolam Cmax ratio
timeFrame: 0-24 hours
measure: Midazolam half-life ratio
timeFrame: 0-24 hours
measure: Omeprazole AUC ratio
timeFrame: 0-24 hours
measure: Omeprazole Cmax ratio
timeFrame: 0-24 hours
measure: Omeprazole half-life ratio
timeFrame: 0-24 hours
Other outcomes:
Locations:
city: Spokane
country: United States
facility: Washington State University College of Pharmacy and Pharmaceutical Sciences
state: Washington
Study officials:
References: