Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
Primary Purpose
Early Menopause, Menopause
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Nitrate supplementation
placebo
Sponsored by
About this trial
This is an interventional prevention trial for Early Menopause focused on measuring Neural control, Cardiovascular function, Inorganic nitrate supplementation
Eligibility Criteria
Inclusion Criteria:
- Healthy normotensive postmenopausal women
- Current age between 60 and 70 years
- Who have experienced "natural" or non-surgical menopause
Exclusion Criteria:
- Any evidence of cardiopulmonary disease
- History of hormone replacement therapy in the last 5 years
- Chronic kidney disease
- Diabetes mellitus
- Hypertension
- Current abuse of alcohol or drugs and use of tobacco products
- Surgical procedure induced menopause
Sites / Locations
- Institute for Exercise and Environmental Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Nitrate supplementation
Placebo
Arm Description
Nitrate rich (6.8 mmol) beet root juice (70ml) twice a day
Nitrate depleted (0.04 mmol) placebo juice (70ml) twice a day
Outcomes
Primary Outcome Measures
Muscle sympathetic nerve activity (MSNA)
Muscle sympathetic nerve activity will be measured using microneurography at the peroneal nerve.
Secondary Outcome Measures
Cardiac Echocardiogram
Systolic and diastolic cardiac function will be measured using high resolution ultrasound echocardiogram
Vascular endothelial function
Brachial artery endothelial function will be measured using flow-mediated dilation
Arterial stiffness/wave properties
Central and peripheral pulse wave velocity and wave reflection will be assessed using arterial tonometry
Full Information
NCT ID
NCT03692572
First Posted
September 25, 2018
Last Updated
February 27, 2023
Sponsor
University of Texas Southwestern Medical Center
Collaborators
Texas Health Resource
1. Study Identification
Unique Protocol Identification Number
NCT03692572
Brief Title
Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
Official Title
Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
August 1, 2018 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
Texas Health Resource
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Women who enter menopause early are at a greater risk for developing cardiovascular disease later in life as compared to women with normal onset of menopause. This increased risk may be due to a prolonged length of time with decreased hormone levels post-menopause; however, this health risk remains understudied. The current study plan to study why women with early menopause are at higher risk for cardiovascular disease by evaluating their sympathetic nervous system and heart-blood vessel function. In addition, there is lack of promising treatment plans for cardiovascular disease in post-menopausal women. Therefore, the current study will also test the impact of dietary nitrate on post-menopausal women to determine if it might serve as a potential treatment to reduce risk of cardiovascular disease in older women.
Detailed Description
The current study is recruiting two groups of women aged between 60-70 years old; 1) women who had early natural/non-surgical menopause (age 40-44 yrs) and 2) women who had normal natural/non-surgical menopause (age 50-54). The investigators are recruiting women who do not have any cardiovascular disease, hypertension, diabetes, and other major health issue.
The main hypothesis of the project is that early menopause negatively impacts the heart, blood vessel and nerve system due to the increased length of time with reduced hormone levels; which could explain the relationship between early menopause and greater risk of cardiovascular disease in later life. Sympathetic nerve system and cardiovascular functions will be evaluated in both groups to compare the impact of prolonged hormone deficiency. In addition, current study will examine the impact of inorganic nitrate supplementation (beet root juice) to see if there are any favorable changes after 2 weeks of beet root juice intake. There are 2 main test visits in the current study.
Visit 1. Nerve system test (maximally take about 5 hours): Participants will rest in the supine position for ≥ 20 mins. Resting heart rate, breathing rate, finger blood pressure will be monitored. Cardiac output will be assessed using the acetylene gas rebreathing technique (1 hour). IV will be inserted for blood draw. Nerve signal search will be performed using a thin needle behind knee to find a signal from a specific nerve. At the same time, transcranial Doppler probe will be placed on the head to look at brain blood flow using soft head gear (1-2 hour). After acceptable signals are obtained, baseline data collection will begin. It will be followed by handgrip exercise and hand immersion to cold water to examine neural sympathetic response to different stimuli (30 mins). After this, to evaluate nerve response to different degrees of passive standings, a bed will be tilted to 30° and 60° for 8 mins each. Blood samples will be obtained in the supine resting position and at the end of 60° tilt (45 mins).
Visit 2. Heart and vessel function assessment (Proximately take 2 hours): All measurements are non-invasive for this visit. Participants will rest in the supine position for ≥ 20 mins. Resting heart function will be assessed by ultrasound echocardiography (30mins). Vascular stiffness measurement will be performed using a probe placed on wrist, neck and leg groin area (30 mins). Vascular endothelial function will be measured using flow-mediated dilation and followed by smooth muscle responsiveness test will be performed by measuring brachial artery diameter changes for 10 min following 0.4 mg sublingual nitroglycerin administration (1 hour).
After Visit 1-2, participant will be asked to drink either dietary nitrate supplementation or placebo for 2 weeks (randomly assigned). After 2 weeks intervention, participant will come back for post-intervention tests which are identical to visit 1 and 2.
After completion of the first intervention, participants will have at least 2 weeks of wash-out period. After 2 weeks participant will be back to the lab and repeat the visit 1 and 2, as well as 2 weeks of dietary nitrate supplementation or placebo. (For those who received 2 weeks of nitrate supplementation for the first intervention, it will be a placebo for this intervention. For those who received placebo for the first intervention, it will be a nitrate supplementation for this intervention). After intervention participants will repeat the visit 1 and 2 again.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Menopause, Menopause
Keywords
Neural control, Cardiovascular function, Inorganic nitrate supplementation
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
2 groups of women (early and normal menopause transition) will be enrolled to crossover design study in a fashion of randomized and double-blinded.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Only research nurse will have an access to the randomization sheet.
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nitrate supplementation
Arm Type
Active Comparator
Arm Description
Nitrate rich (6.8 mmol) beet root juice (70ml) twice a day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Nitrate depleted (0.04 mmol) placebo juice (70ml) twice a day
Intervention Type
Dietary Supplement
Intervention Name(s)
Nitrate supplementation
Intervention Description
Subjects will drink 70 ml of beet root juice twice a day for 2 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
placebo
Intervention Description
Subjects will drink 70 ml of nitrate depleted placebo juice twice a day for 2 weeks.
Primary Outcome Measure Information:
Title
Muscle sympathetic nerve activity (MSNA)
Description
Muscle sympathetic nerve activity will be measured using microneurography at the peroneal nerve.
Time Frame
Change from baseline resting MSNA to 2 weeks post nitrate supplementation resting MSNA
Secondary Outcome Measure Information:
Title
Cardiac Echocardiogram
Description
Systolic and diastolic cardiac function will be measured using high resolution ultrasound echocardiogram
Time Frame
Change from baseline cardiac function to 2 weeks post nitrate supplementation resting cardiac function
Title
Vascular endothelial function
Description
Brachial artery endothelial function will be measured using flow-mediated dilation
Time Frame
Change from baseline brachial artery endothelial function to 2 weeks post nitrate supplementation brachial artery endothelial function
Title
Arterial stiffness/wave properties
Description
Central and peripheral pulse wave velocity and wave reflection will be assessed using arterial tonometry
Time Frame
Change from baseline pulse wave velocity and wave reflection to 2 weeks post nitrate supplementation resting pulse wave velocity and wave reflection
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy normotensive postmenopausal women
Current age between 60 and 70 years
Who have experienced "natural" or non-surgical menopause
Exclusion Criteria:
Any evidence of cardiopulmonary disease
History of hormone replacement therapy in the last 5 years
Chronic kidney disease
Diabetes mellitus
Hypertension
Current abuse of alcohol or drugs and use of tobacco products
Surgical procedure induced menopause
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qi Fu, Ph.D.
Organizational Affiliation
Faculty
Official's Role
Study Director
Facility Information:
Facility Name
Institute for Exercise and Environmental Medicine
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
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