Resveratrol in Postmenopausal Women With High Body Mass Index - Full Text View

Purpose

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.

Condition	Intervention	Phase
Healthy, no Evidence of Disease	Drug: resveratrol Other: laboratory biomarker analysis	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Pilot Study of Resveratrol in Postmenopausal Women With High Body Mass Index

Resource links provided by NLM:

Drug Information available for: Resveratrol

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Change in serum estradiol levels in postmenopausal women with high BMI [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change in serum estrone [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum testosterone [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum sex hormone-binding globulin (SHBG) [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum levels of insulin [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum levels of C-peptide [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum leptin [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in serum adiponectin [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in inflammatory markers, measured by serum C-reactive protein [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in urinary 8-iso-PGF2alpha [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Change in urinary 8OHdG [ Time Frame: From baseline to 12 weeks (post-intervention) ] [ Designated as safety issue: No ]
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.
Incidence of reported adverse events [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals.
Incidence of changes in CBC/diff, blood chemistry, and lipids [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
Study agent/metabolite levels [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
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.


Enrollment:	46
Study Start Date:	June 2011
Study Completion Date:	July 2012
Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Basic Science (resveratrol) Patients receive resveratrol PO QD for 12 weeks.	Drug: resveratrol Given PO Other: laboratory biomarker analysis Correlative studies

Detailed Description:

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

Eligibility


Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370889

Locations


United States, Arizona
Arizona Cancer Center - Tucson
Tucson, Arizona, United States, 85724-5024
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Hsiao-Hui (Sherry) Chow	University of Arizona Health Sciences Center

More Information

No publications provided


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01370889 History of Changes
Obsolete Identifiers:	NCT02022332
Other Study ID Numbers:	NCI-2011-02593, NCI-2011-02593, CDR0000701405, 10-0653-04, UAZ08-12-01, P30CA023074, N01CN35158
Study First Received:	June 9, 2011
Last Updated:	October 8, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Resveratrol Analgesics Analgesics, Non-Narcotic Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal Anticarcinogenic Agents Antimutagenic Agents Antineoplastic Agents Antineoplastic Agents, Phytogenic Antioxidants Antirheumatic Agents	Central Nervous System Agents Enzyme Inhibitors Hematologic Agents Molecular Mechanisms of Pharmacological Action Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Platelet Aggregation Inhibitors Protective Agents Sensory System Agents Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015