Resveratrol in Healthy Adult Participants

Healthy, no Evidence of Disease Clinical Trial

Official title:

Clinical Study of Resveratrol on Drug and Carcinogen Metabolizing Enzymes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721877
• Other study ID #: NCI-2009-00895
• Secondary ID: NCI-2009-0089507
• Status: Completed
• Phase: Phase 1
• First received: July 24, 2008
• Last updated: October 7, 2014
• Start date: August 2008
• Est. completion date: July 2009

Study information

• Verified date: March 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Healthy, no Evidence of Disease

Intervention

Drug:
• resveratrol
Given orally

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Arizona Cancer Center - Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	Yes