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

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.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Drug: Placebo patch; Dietary supplement: Resveratrol; Dietary supplement: Placebo; Drug: Climara

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo patch - placebo tablets; 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; Placebo patch designed to match active Climara patches.; Dietary supplement: Placebo; Placebo tablets designed to match active resveratrol tablets.
EXPERIMENTAL: Placebo patch - Resveratrol tablets; 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; Placebo patch designed to match active Climara patches.; Dietary supplement: Resveratrol
ACTIVE_COMPARATOR: Climara patch - placebo tablets; 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.	Dietary supplement: Placebo; Placebo tablets designed to match active resveratrol tablets.; Drug: Climara; Other Names: Estradiol transdermal patch

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Kerrie L Moreau, PhD, University of Colorado School of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): March 25, 2016
• Study Completion (ACTUAL): March 25, 2016

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 1, 2014
• First Posted (ESTIMATE): October 3, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens; Antioxidants; Estradiol; Resveratrol
• Other Study ID Numbers: 14-0532; UL1TR001082 (U.S. NIH Grant/Contract); R56HL114073 (NIH)