Resveratrol in Healthy Adult Participants

Study Overview
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Brief Summary
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Resveratrol may prevent cancer in healthy people. Studying samples of blood and urine in the laboratory from participants who are taking resveratrol may help doctors learn more about how this drug is used by the body. This phase I trial is studying the side effects of resveratrol and to see how it works in healthy adult participants.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the effect of resveratrol on human cytochrome P450 (CYP) enzyme activity in healthy adult participants. SECONDARY OBJECTIVES: I. To determine the modulation effect on phase II detoxification enzymes. II. To evaluate safety in participants treated with this drug. OUTLINE: Participants receive oral resveratrol once daily for 4 weeks. Patients complete a daily diary documenting adverse events and an intake calendar for recording the daily intake of any non-routine medications. Participants undergo blood sample collection periodically. Lymphocytes are isolated and analyzed for baseline GST activity and level. Serum is analyzed to determine bilirubin levels to be used as surrogate UGT 1A1 activity. Analyses of CYP probe drugs will be performed using high performance liquid chromatography (HPLC) assays. A sensitive ELISA assay will be used for quantitative analyses. Urine samples are collected periodically and drug and metabolite levels will be analyzed. After completion of study treatment, participants are followed for 2 weeks.

Official Title
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Clinical Study of Resveratrol on Drug and Carcinogen Metabolizing Enzymes

Conditions
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Healthy, no Evidence of Disease

Intervention / Treatment
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* Drug: resveratrol
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Criteria: Healthy adult participants meeting the following criteria: Limit cruciferous vegetables to no more than one serving each week for about 6 weeks Limit resveratrol-containing foods (i.e., wine, peanuts, mulberries, grapes, cranberries, blueberries, and huckleberries) to no more than one serving each per day for about 6 weeks No caffeine-containing food or beverages (e.g., coffee, colas, chocolate, or over-the-counter medications) or food items that have been reported to affect drug/carcinogen metabolizing enzymes (e.g., grapefruit, grapefruit juice, cruciferous vegetables, and food cooked over charcoal) beginning 72 hours before and until 8 hours after each set of CYP probe drug administration Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,500/uL Platelet count >= 100,000/uL Total bilirubin =< 2.0 mg/dL AST/ALT =< 1.5 times upper limit of normal (ULN) Creatinine =< ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must have a resting systolic blood pressure >= 100 mm Hg at screening and prior to probe drug administration Must not consume more than three drinks of alcohol per week on average No prior invasive cancers (i.e., non-skin cancer) within the past 5 years No history of allergic reactions to resveratrol-containing products or CYP probe drugs (e.g, caffeine, dextromethorphan, losartan, or buspirone) No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation that would limit compliance with study requirements No over-the-counter medications beginning 72 hours before and until 8 hours after each CYP probe drug administration No participation in another clinical intervention trial within the past 3 months No concurrent medications or supplements that are known CYP enzyme inducers or inhibitors No concurrent herbal medicines, dietary supplements, or above-standard vitamins or minerals (a standard daily multivitamin or mineral supplement is acceptable) Non-smoking, defined as not currently smoking or stopped smoking more than 1 year ago Normal liver and renal function Able and willing to adhere to the following dietary restrictions: ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Participants receive oral resveratrol once daily for 4 weeks. | Drug: resveratrol<br>* Given orally<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modulation of CYP enzyme activities | Will be assessed by a comparison of CYP enzyme activities from baseline to end of resveratrol intervention. CYP1A2, 2D6, 2C9, and 3A4 activity will be assessed by plasma paraxanthine/caffeine ratio, urinary dextromethorphan/dextrophan ratio, urinary losartan/losartan metabolite ratio, and area under the plasma buspirone concentration-time curve, respectively. The primary analysis will consist of paired t-tests of differences in log values from baseline to end of intervention (equivalent to log of the ratio). | From baseline to end of resveratrol intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Phase II enzyme activity | GST activity and GST-pi level in blood lymphocytes and serum bilirubin levels will be used to assess Phase II enzyme activity. Paired t-tests of differences in values from baseline to end of intervention will be used, with a 2-sided significance level of 0.0167 for the three tests. | From baseline to end of resveratrol intervention | 
| Safety evaluation using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 | Any adverse events will be presented descriptively. | Up to 6 weeks |