Resveratrol in Healthy Adult Participants

Clinical Study of Resveratrol on Drug and Carcinogen Metabolizing Enzymes

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.

Study Overview

• Status: Completed
• Conditions: Healthy, no Evidence of Disease
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: resveratrol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center - Tucson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Participants receive oral resveratrol once daily for 4 weeks.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: resveratrol; Given orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Hsiao-Hui (Sherry) Chow, Arizona Cancer Center - Tucson

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: July 24, 2008
• First Submitted That Met QC Criteria: July 24, 2008
• First Posted (Estimate): July 25, 2008

Study Record Updates

• Last Update Posted (Estimate): October 8, 2014
• Last Update Submitted That Met QC Criteria: October 7, 2014
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: NCI-2009-00895 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA023074 (U.S. NIH Grant/Contract); N01CN35158 (U.S. NIH Grant/Contract); 07-0376-04 (Other Identifier: Arizona Cancer Center - Tucson); BIO07-054; CDR0000656389; UAZ06-8-01 (Other Identifier: DCP)