Resveratrol in Postmenopausal Women With High Body Mass Index

Study Overview
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Brief Summary
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This pilot phase I trial studies resveratrol in postmenopausal women with high body mass index. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of resveratrol may keep cancer from forming. Studying samples of blood and urine in the laboratory from postmenopausal women who are taking resveratrol may help doctors learn more about the effects of resveratrol on biomarkers.

Detailed Description
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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

Official Title
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Pilot Study of Resveratrol in Postmenopausal Women With High Body Mass Index

Conditions
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Healthy, no Evidence of Disease

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Basic Science (resveratrol)<br>Patients receive resveratrol PO QD for 12 weeks. | Drug: resveratrol<br>* Given PO<br>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 |
| --- | --- | --- |
| Change in serum estradiol levels in postmenopausal women with high BMI | A two-sided paired t-test will be performed to determine whether the change is significant at a significance level of 5%. If the data distribution indicates non-normality or skewedness in violation of the assumptions of the t-test, non-parametric tests will be used. Linear regression techniques will be used to adjust for potential confounders, e.g. age and BMI. | From baseline to 12 weeks (post-intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum estrone | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum testosterone | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum sex hormone-binding globulin (SHBG) | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum levels of insulin | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum levels of C-peptide | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum leptin | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in serum adiponectin | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in inflammatory markers, measured by serum C-reactive protein | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in urinary 8-iso-PGF2alpha | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Change in urinary 8OHdG | Similar statistical analysis procedures as described for the primary endpoint will be performed to evaluate the changes of each of the endpoints at a significance level of 5%. Analysis will not be corrected for multiple comparisons but results will be interpreted cautiously. If the data distribution indicates non-normality or skewness, non-parametric tests will be used. | From baseline to 12 weeks (post-intervention) | 
| Incidence of reported adverse events | Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals. | Up to 12 weeks | 
| Incidence of changes in CBC/diff, blood chemistry, and lipids |  | Up to 12 weeks | 
| Study agent/metabolite levels | The Spearman correlation coefficient will be calculated to evaluate the correlation between biomarker changes and study agent/metabolite levels. Linear regression techniques will be used to adjust for potential confounders, e.g. age and BMI. | Up to 12 weeks |