Postmenopausal Women and Their Endothelium

Postmenopausal Women and Their Endothelium: Is Dietary Nitrate Supplementation Protective

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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Women
• Intervention / Treatment: Drug: nitrate rich beetroot juice; Drug: nitrate depleted beetroot juice

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Penn State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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:

  1. blood pressure lowering medication (e.g., beta blockers, ACE inhibitors, angiotensin antagonists, calcium channel blockers, diuretics)
  2. lipid- lowering medication (e.g., statins)
  3. nitrates (e.g. nitroglycerin) for angina
  4. phosphodiesterase inhibitors (e.g., Viagra)
  5. anti-Inflammatory drugs
• Individuals taking hormone therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nitrate rich beetroot juice; Subjects will consume 140 ml of beetroot juice (Beet-It Organic Shot) approximately 90 min before physiological testing.	Drug: nitrate rich beetroot juice; This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).; Other Names: Beet-It Organic Shot
Placebo Comparator: Nitrate depleted beetroot juice; Subjects will consume 140 ml of beetroot juice (Beet-It Organic Placebo) approximately 90 min before physiological testing.	Drug: nitrate depleted beetroot juice; 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).; 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.

Collaborators and Investigators

• Sponsor: Penn State University
• Investigators: Principal Investigator: David N Proctor, PhD, Penn State University

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Actual): February 20, 2023
• Study Completion (Actual): February 20, 2023

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 23, 2018

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: beetroot juice; dietary nitrate supplementation
• Other Study ID Numbers: 00010017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No