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Completed

NCT Number: NCT01173640

Resveratrol and Midazolam Metabolism

Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been identified in over 70 species and is suggested to be the constituent in red wine responsible for cardioprotective effects. The potential health benefits of resveratrol supplements are highly extolled in the alternative medicine industry and daily doses are up to 5 grams are being studied. While there are potential health benefits of high doses of resveratrol, for patients taking other drugs metabolized by CYP3A4, such as transplant medications, chemotherapies and HMG-CoA reductase inhibitors, there may be a clinically significant herb-drug interaction.

We, the investigators, have shown in vitro that resveratrol is a mechanism-based inhibitor of cytochrome P450 3A4 (CYP3A4). Based on our in vitro evidence and literature reports of the pharmacokinetics of resveratrol, we hypothesize that resveratrol will be a potent in vivo mechanism-based inhibitor of intestinal CYP3A4 enzymes. To date, there are no clinical studies that address the potential for a resveratrol-drug interaction. We propose to test whether single and multiple doses of resveratrol alter the pharmacokinetics of midazolam, a prototypic CYP3A4 probe drug.

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Key information

Conditions

Healthy

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Washington

Seattle, Washington, 98195, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18 to 50 years old.
  • Body mass index between 18 and 30 kg/m2.
  • Good health without a self-reported history of liver, kidney, gastrointestinal or heart disease
  • Women use measures to avoid conception during the study period (e.g. oral contraceptives, intrauterine devices [IUDs], and condoms)
  • Subjects must agree not to take any known substrates, inhibitors, inducers or activators of CYP3A4 at least 2 weeks before study start and for the entire duration of the study.
  • Avoid ingesting grapefruit, grapefruit juice or other grapefruit juice containing products, and any herbal-based nutrient supplement or prescribed medications during the same period of time.
  • Willing to fast overnight before the study days.
  • Willing to abstain from alcohol-containing beverages 24 hours before and during the study visits, and willing to abstain from grapefruit, cranberry, blueberry products, peanuts and peanut butter, grape and grape products, and red wine at least one week prior to and during the study.

Exclusion criteria

  • Current cigarette smoker
  • Self-reported history of liver, kidney, gastrointestinal or heart disease
  • Abnormal liver or kidney function tests based on the Comprehensive and Hepatic Panel (below the lower end or greater than 15% of the upper end of the reference range).
  • Known or suspected history of alcohol or drug abuse
  • Allergic to benzodiazepines or any other chemically related drugs
  • Women who are pregnant or breastfeeding
  • Recent ingestion (<1 week) of any medication known to be metabolized by CYP3A4 or alter CYP3A activity
  • Chronic use of prescription drugs, over-the-counter, vitamins or natural products. However, oral contraceptives will be permitted.
  • Unable to give informed consent
  • Participated in another clinical trial or study within 30 days

Treatment and study plan

midazolam

Drug

2 mg oral dose

Other names: Versed

resveratrol (single dose)

Dietary Supplement

1 g oral dose

resveratrol (multiple dose)

Dietary Supplement

1 g oral dose for 8 days

Primary outcomes

  1. Inhibition of midazolam clearance

    Time frame: 3 study visit days

    The primary aim will be to determine if resveratrol causes inhibition of intestinal and hepatic CYP3A4 enzymes as determined by oral midazolam clearance following single and multiple doses of resveratrol, respectively.

Secondary outcomes

  1. Resveratrol accumulation

    Time frame: 3 study visit days

    Secondary aims will be to measure circulating levels of resveratrol and its conjugated metabolites following single and multiple doses of resveratrol and to determine resveratrol accumulation in low density lipoproteins (LDL).

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Collaborators

  • Bastyr University

Registry information

Important dates

Study start
2010
Primary completion
2011
Study completion
2011
First posted
Aug 2, 2010
Registry last updated
Oct 31, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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