Resveratrol in Postmenopausal Women With High Body Mass Index

PRIMARY OBJECTIVES:

I. To determine the effect of pharmacological doses of resveratrol on serum estradiol levels in post-menopausal women with high body mass index (BMI).

SECONDARY OBJECTIVES:

I. Assess the effect of resveratrol on serum estrone, testosterone, and sex hormone-binding globulin (SHBP).

II. Assess the effect of resveratrol on serum levels of insulin and C-peptide. III. Assess the effect of resveratrol on adipocytokine expression and secretion as measured by serum leptin and adiponectin.

IV. Assess the effect of resveratrol on inflammatory cytokines as measured by serum C-reactive protein (CRP).

V. Assess the effect of resveratrol on oxidative stress as measured by urinary 8-isoprostaglandin F2 alpha (8-iso-PGF2 alpha) and 8-hydroxydeoxyguanosine (8OHdG).

VI. Assess the safety of resveratrol intervention as measured by reported adverse events, complete blood count with differential (CBC/diff), comprehensive metabolic panel (CMP), and lipid profile.

VII. Assess the relationship between systemic study agent exposure and biomarker modulation.

OUTLINE:

Patients receive resveratrol orally (PO) once daily (QD) for 12 weeks.

After completion of study therapy, patients are followed up for 2 weeks

Inclusion criteria

• Healthy postmenopausal women with a body mass index (BMI) of 25 kg/m^2 or greater
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Karnofsky 70% or above
• Leukocytes >= 3,000/uL
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 2.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 times upper limit of normal (ULN)
• Creatinine =< 1.0 times ULN
• Ability and willingness to limit resveratrol-containing foods to no more than one serving each per day for about 14 weeks
• Negative mammogram or negative workup of mammographic findings within prior 12 months prior to enrollment for women >= 50 years of age
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Have had invasive cancer(s) within the past 5 years except non-melanoma skin cancer
• Within 3 months of or concurrent usage of any other investigational agents
• History of allergic reactions attributed to resveratrol
• Unwilling or unable to refrain from taking herbal medicines and dietary supplements
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Within 3 months of or concurrent estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens; vaginal estrogen is acceptable.

Within 3 months of or concurrent usage of tamoxifen, raloxifene, other selective estrogen-receptor modulators, or aromatase inhibitors

• Regular usage (more than 2 times a week) of estrogenic supplements or herbal remedies (e.g., Remifemin, black cohosh, red clover, dong quai, soy isoflavones, dehydroepiandrosterone [DHEA], flaxseed, diindolylmethane [DIM], genistein, and daidzein) within the past 3 months or concurrently; dietary consumption of phytoestrogens/isoflavones (such as soy, tofu, millet, barley, natto, tempeh, miso, soy milk, soy sauce) is acceptable as these sources are not concentrated
• Concurrent use of anti-diabetic drugs such as:

• Insulin
• Sulfonylureas (e.g., glipizide, glyburide, or glimepiride)
• Meglitinides (e.g., repaglinide or nateglinide)
• Biguanides (e.g., metformin)
• Thiazolidinediones (e.g., rosiglitazone or pioglitazone)
• Alpha-glucosidase inhibitors (e.g., acarbose or miglitol)
• Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin)
• Concurrent use of warfarin or phenytoin