Endothelial Dysfunction
Conditions
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.
Interventions
DRUGClimara
DRUGPlacebo patch
Placebo patch designed to match active Climara patches.
DIETARY_SUPPLEMENTResveratrol
DIETARY_SUPPLEMENTPlacebo
Placebo tablets designed to match active resveratrol tablets.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | Up to 2 hours post-exercise | Brachial artery flow-mediated dilation represents the percent change in artery diameter (before and after blood pressure cuff inflation-deflation) within each time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gene and Protein Expression in Peripheral Blood Mononuclear Cells | baseline, 1-2 hours post-exercise | No gene and protein data were analyzed. |
| Change in Nitrate/Nitrite Levels | baseline, 1-2 hrs post-exercise | Measure of nitric oxide |
Countries
United States
Participant flow
Recruitment details
Healthy women ages 50-70 years, at least 1 year beyond menopause and free of overt cardiovascular or chronic diseases.
Pre-assignment details
7 participants did not qualify to participate in the study after consent/enrollment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Back pain preventing exercise | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: Up to 2 hours post-exercise
Population: Images were considered invalid and removed from analysis if the vascular boundaries were not able to be identified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | Baseline | 4.11 Percent Change | Standard Error 0.44 |
| Placebo Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 30 min after exercise | 3.20 Percent Change | Standard Error 0.45 |
| Placebo Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 60 min after exercise | 3.23 Percent Change | Standard Error 0.44 |
| Placebo Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 120 min after exercise | 4.35 Percent Change | Standard Error 0.44 |
| Placebo Patch - Resveratrol Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 120 min after exercise | 7.57 Percent Change | Standard Error 0.81 |
| Placebo Patch - Resveratrol Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | Baseline | 6.93 Percent Change | Standard Error 0.79 |
| Placebo Patch - Resveratrol Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 60 min after exercise | 7.01 Percent Change | Standard Error 0.79 |
| Placebo Patch - Resveratrol Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 30 min after exercise | 5.88 Percent Change | Standard Error 0.81 |
| Climara Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 120 min after exercise | 8.03 Percent Change | Standard Error 0.65 |
| Climara Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 30 min after exercise | 5.41 Percent Change | Standard Error 0.67 |
| Climara Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | 60 min after exercise | 6.99 Percent Change | Standard Error 0.69 |
| Climara Patch - Placebo Tablets | Percent Change in Brachial Artery Flow-mediated Dilation at Each Time Point | Baseline | 5.86 Percent Change | Standard Error 0.65 |
Secondary
Change in Nitrate/Nitrite Levels
Measure of nitric oxide
Time frame: baseline, 1-2 hrs post-exercise
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | 60 min after exercise | 108.6 micromolar | Standard Deviation 48.5 |
| Placebo Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | Baseline | 121.3 micromolar | Standard Deviation 57.6 |
| Placebo Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | 120 min after exercise | 114.7 micromolar | Standard Deviation 54.2 |
| Placebo Patch - Resveratrol Tablets | Change in Nitrate/Nitrite Levels | 60 min after exercise | 109.6 micromolar | Standard Deviation 59.2 |
| Placebo Patch - Resveratrol Tablets | Change in Nitrate/Nitrite Levels | Baseline | 134.2 micromolar | Standard Deviation 65.6 |
| Placebo Patch - Resveratrol Tablets | Change in Nitrate/Nitrite Levels | 120 min after exercise | 118.7 micromolar | Standard Deviation 56 |
| Climara Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | Baseline | 110.9 micromolar | Standard Deviation 53.5 |
| Climara Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | 120 min after exercise | 111.1 micromolar | Standard Deviation 60.6 |
| Climara Patch - Placebo Tablets | Change in Nitrate/Nitrite Levels | 60 min after exercise | 118.2 micromolar | Standard Deviation 61.1 |
Secondary
Gene and Protein Expression in Peripheral Blood Mononuclear Cells
No gene and protein data were analyzed.
Time frame: baseline, 1-2 hours post-exercise
Population: No data were collected for this outcome measure.