The Effects of Resveratrol and Acute Exercise on Endothelial Function in Postmenopausal Women

Study Overview
=================
Brief Summary
-----------------
This pilot study plans to learn more about the aging of blood vessels and arteries in women. As women age and go through menopause, their risk for cardiovascular disease increases. Also with aging and menopause, levels of the reproductive hormone estradiol decline. Hormone replacement therapy to restore estradiol levels does not protect women from cardiovascular disease, so lifestyle changes, such as regular exercise, are recommended to reduce disease risk. However, there are differences between men and women in their response to exercise. In older men, exercise improves the health of their arteries, but in postmenopausal women, exercise does not provide this benefit. The purpose of this pilot study is to determine whether low estradiol levels in postmenopausal women are responsible for the poor vascular response to exercise. In this study the investigators will also test whether treatment with resveratrol, a plant compound found in red wine, improves postmenopausal women's response to exercise. The investigators hypothesize that acute treatment with estrogen or resveratrol will improve vascular responses to an acute bout of exercise.

Official Title
-----------------
The Effects of Resveratrol and Acute Exercise on Endothelial Function in Postmenopausal Women

Conditions
-----------------
Endothelial Dysfunction

Intervention / Treatment
-----------------
* Drug: Climara
* Drug: Placebo patch
* Dietary Supplement: Resveratrol
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between the ages of 50-70 and at least 1 year beyond menopause; resting blood pressure <140/90 mmHg; plasma glucose concentrations <110 mg/dL under fasting conditions; BMI < 35; LDL cholesterol < 160 mg/dL; sedentary or recreationally active (<3 days of vigorous aerobic exercise); no use of OCs, HT, or other medications that might influence cardiovascular function; nonsmokers; no use of vitamin supplements, blood thinners or NSAIDS, or willing to stop use one month prior to and for the duration of the study; not taking any other medications that would interact with E2 patch or resveratrol to confound interpretation of results. Exclusion Criteria: history of or active E2-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia (≥ 150 mg/dL), and CVD; known allergy to transdermal patch, or resveratrol; history of stomach ulcer or bleeding; other contraindications to HT or resveratrol. other conditions for which individuals will be excluded from the study include: diabetes, active infection, history of seizures or disease that affects the nervous system or an abnormal resting ECG.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo patch - placebo tablets<br>Postmenopausal women will be given a placebo patch to wear two days prior to exercise visit and a placebo tablet to take the morning of the exercise visit. | Drug: Placebo patch<br>* Placebo patch designed to match active Climara patches.<br>Dietary Supplement: Placebo<br>* Placebo tablets designed to match active resveratrol tablets.<br>|
| Experimental: Placebo patch - Resveratrol tablets<br>Postmenopausal women will be given a placebo patch to wear for two days prior to the exercise visit and a resveratrol tablet (dosed at 250mg) to take the morning of the exercise visit. | Drug: Placebo patch<br>* Placebo patch designed to match active Climara patches.<br>Dietary Supplement: Resveratrol<br> <br> |
| Active Comparator: Climara patch - placebo tablets<br>Postmenopausal women will be given a transdermal estrogen patch to wear (0.05mg/day) for two days prior to the exercise visit and a placebo tablet to take the morning of the exercise visit. | Drug: Climara<br> <br> * Other names: Estradiol transdermal patch;Dietary Supplement: Placebo<br>* Placebo tablets designed to match active resveratrol tablets.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | Brachial artery flow-mediated dilation represents the percent change in artery diameter (before and after blood pressure cuff inflation-deflation) within each time point. | Up to 2 hours post-exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene and Protein Expression in Peripheral Blood Mononuclear Cells | No gene and protein data were analyzed. | baseline, 1-2 hours post-exercise | 
| Change in Nitrate/Nitrite Levels | Measure of nitric oxide | baseline, 1-2 hrs post-exercise |