The Effect of Grape Seed Extract on Estrogen Levels of Postmenopausal Women

Study Overview
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Brief Summary
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The role of estrogens in the pathogenesis of breast cancer has been well documented. This has led to the development of Anti-Estrogens (selective estrogens receptor modulators and Aromatase Inhibitors), used for treatment and prevention of breast cancer. These agents, however, have significant side effects, which are not acceptable to many healthy high-risk women. There is preliminary evidence that grape seed extract acts as natural aromatase inhibitor (1). This study has the potential to quantify the effectiveness of a natural substance that mimics the action of pharmaceutical aromatase inhibitors.

Detailed Description
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Early detection of breast cancer with screening mammography and the use of more effective medical therapies have led to a decrease in breast cancer mortality. However, breast cancer is still the second leading cause of cancer death in women (2). Therefore, the future lies in not only early detection but prevention of breast cancer. Currently available chemopreventive agents are associated with potentially serious side effects and can be quite costly, especially when taken for extended periods of time. Therefore, they are usually targeted only to women at high risk of disease. Identification of an inexpensive, efficacious preventive therapy with few or no side effects would represent a major advance in reducing the morbidity and mortality due to breast cancer. One exciting possibility is grape seed extract. Grapes and grape seeds contain procyanidins, a highly active subclass of flavonoids with actions similar to pharmaceutical aromatase inhibitors (AIs). These procyanidin dimers have been found to suppress estrogen biosynthesis both in vitro and in animal models (1). Based upon this knowledge we proposed this dose finding pilot study.

Official Title
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The Effect of Grape Seed Extract on Estrogen Levels of Postmenopausal Women: A Pilot Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Dietary Supplement: Grape Seed Extract
* Dietary Supplement: Grape Seed Extract
* Dietary Supplement: Grape Seed Extract
* Dietary Supplement: Grape Seed Extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 55 - 75 years Able to understand and sign a consent form Postmenopausal (no menstrual period for 1 year or more) No personal cancer history (except for non-melanoma skin cancer) No hormone replacement therapy or anti-estrogens within 6 months of baseline Exclusion Criteria: Known allergy to grapes or grape products Currently on ACE inhibitors, methotrexate, allopurinol, coumadin (Warfarin, Jantoven), heparin, clopidogrel (Plavix), or cholesterol lowering medication

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Grape Seed Extract # 1<br>200 mg [1 pill] | Dietary Supplement: Grape Seed Extract<br>* 200 mg dose daily for 12 weeks.<br>* Other names: ActiVin®;|
| Active Comparator: Grape Seed Extract # 2<br>200 mg [2 pills] | Dietary Supplement: Grape Seed Extract<br>* 400 mg dose daily for 12 weeks.<br>* Other names: ActiVin®;|
| Active Comparator: Grape Seed Extract # 3<br>200 mg [3 pills] | Dietary Supplement: Grape Seed Extract<br>* 600 mg dose daily for 12 weeks.<br>* Other names: ActiVin®;|
| Active Comparator: Grape Seed Extract # 4<br>200 mg [4 pills] | Dietary Supplement: Grape Seed Extract<br>* 800 mg dose daily for 12 weeks.<br>* Other names: ActiVin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To document that grape seed extract taken orally will decrease plasma estrogen levels (estrone (E1), estradiol (E2), and E1-conjugates) and increase precursor androgen levels (testosterone and androstenedione) in healthy postmenopausal women. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the most effective, well tolerated dose of grape seed extract resulting in a decrease in plasma estrogen levels (E1, E2, E1-conjugates) and increase in precursor androgens (testosterone and androstenedione). |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Grape Seed Extract, Breast Cancer, Estrogen Levels, Aromatase Inhibitor