Postmenopausal Women and Their Endothelium

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the effects of a one time dose and 7-days of inorganic nitrate (supplied in the form of beetroot juice) on blood vessel function and resting blood pressure in healthy, postmenopausal women. Participants will drink beetroot juice and a placebo juice on separate visits where blood pressure and blood vessel function will be measured.

Detailed Description
-----------------
Cardiovascular disease is the leading cause of death in the United States. Due to the loss of estrogen, women experience a unique accelerated rise in cardiovascular disease risk factors following menopause. Postmenopausal women represent a population at heightened risk for cardiovascular disease development. Function of the endothelium has been shown to decline across the menopause transition, resulting in less production of nitric oxide. As such the investigators are investigating a potential therapeutic strategy in women have recently undergone menopause to boost nitric oxide availability.

Official Title
-----------------
Postmenopausal Women and Their Endothelium: Is Dietary Nitrate Supplementation Protective

Conditions
-----------------
Postmenopausal Women

Intervention / Treatment
-----------------
* Drug: nitrate rich beetroot juice
* Drug: nitrate depleted beetroot juice


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Early post-menopausal women who are within 1-6 years following their final menstrual cycle Late post-menopausal women who are beyond 6 years following their final menstrual cycle Exclusion Criteria: Individuals with any overt cardiovascular, metabolic, hematologic, pulmonary, renal, musculoskeletal, and/or neurological disease(s). Users of any tobacco and/or nicotine products (smokers, chewing tobacco, nicotine-containing patches/gum, smokeless cigarettes) Individuals with a BMI > 35 Individuals with resting blood pressure > or = 130/80 mm Hg Individuals with high blood lipids (total cholesterol > or = 240 mg/dl, LDL > or = 160 mg/dl, triglycerides > or = 200 mg/dl). Postmenopausal women with hyperglycemia (fasting glucose > or = 110 mg/dl and HbA1c >6.0%). Individuals taking any of the following medications: blood pressure lowering medication (e.g., beta blockers, ACE inhibitors, angiotensin antagonists, calcium channel blockers, diuretics) lipid- lowering medication (e.g., statins) nitrates (e.g. nitroglycerin) for angina phosphodiesterase inhibitors (e.g., Viagra) anti-Inflammatory drugs Individuals taking hormone therapy

Ages Eligible for Study
-----------------
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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitrate rich beetroot juice<br>Subjects will consume 140 ml of beetroot juice (Beet-It Organic Shot) approximately 90 min before physiological testing. | Drug: nitrate rich beetroot juice<br>* This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).<br>* Other names: Beet-It Organic Shot;|
| Placebo Comparator: Nitrate depleted beetroot juice<br>Subjects will consume 140 ml of beetroot juice (Beet-It Organic Placebo) approximately 90 min before physiological testing. | Drug: nitrate depleted beetroot juice<br>* This beverage is identical in look and taste to the Beet-It organic shot, but has the nitrate removed. It is also bottled and supplied by James White Drinks (UK).<br>* Other names: Beet-it Organic Shot Placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macro-vascular reactivity | Using near-infrared spectroscopy, a probe placed on the forearm muscle will be used to measure the tissue saturation index re-perfusion slope following 5 minutes of forearm cuff occlusion. | These measurements will take place before and after a ischemia-reperfusion injury (20 minutes inflation, 20 minutes deflation) induced in the upper arm to assess change in macro-vascular reactivity | 
| Micro-vascular reactivity | Using near-infrared spectroscopy, a probe placed on the forearm muscle will be used to measure area under the curve for tissue saturation index re-perfusion following 5 minutes of forearm cuff occlusion. | These measurements will take place before and after a ischemia-reperfusion injury (20 minutes inflation, 20 minutes deflation) induced in the upper arm to assess change in micro-vascular reactivity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting blood pressures | Resting systolic blood pressures will be measured in the arm (cuff) and estimated in the aorta (radial artery tonometry). | Change from baseline resting blood pressure and at 90 minutes after beet root juice ingestion | 
| Recovery of micro-vascular function and brachial artery flow mediated dilation | Micro-vascular and brachial artery flow-mediated dilation, as described above, will be reassessed 30 minutes following ischemia-reperfusion injury to determine recovery of vessel function. | Change in these measures from immediately after ischemia-reperfusion injury to 30 minutes following | 
| Brachial artery flow-mediated dilation | Using doppler ultrasound the brachial artery diameter will be measured before and after 5 minutes of forearm cuff occlusion | These measurements will take place before and after a ischemia-reperfusion injury (20 minutes inflation, 20 minutes deflation) induced in the upper arm to assess change in brachial artery flow-mediated dilation | 
| Brachial ankle pulse wave velocity and ankle-brachial index | Using the VP-Colin 2000 brachial ankle pulse wave velocity and ankle brachial index will be measured before and after supplementation | These measurements will take place before (day 1) and 24 hours after (day 8) 7 days of supplementation. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dietary nitrate supplementation, beetroot juice