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NCT Number: NCT06480695

Exercise Training Intensity and Nitrate Supplementation in Post-Menopausal Females

Menopause greatly increases cardiovascular disease risk (CVD). Current exercise guidelines are inadequate to ameliorate this risk and higher intensity exercise may be necessary for cardiovascular benefits in postmenopausal females. Oral nitrate supplementation enhances exercise performance and CVD risk profile in several clinical conditions. The investigators recently reported that 3-days of nitrate supplementation in postmenopausal females enhances acute post-exercise vascular function, in an intensity dependent manner. The effects of nitrate supplementation and exercise training over a longer training program remains unexplored. This investigation will examine the impact of exercise training intensity with and without inorganic nitrate supplementation, on CVD and fitness outcomes. Postmenopausal females will be tested for maximal oxygen uptake and lactate threshold before randomization to one of four groups: that inorganic nitrate-rich beetroot juice, or beetroot juice with nitrate extracted; and assigned to one-month of calorie matched high-intensity or moderate-intensity exercise training. Vascular function and fitness will be evaluated before and after training.

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Key information

Conditions

Menopause

Age range

45 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Student Health and Wellness Building - Department of Kinesiology

Charlottesville, Virginia, 22903, United States

Location status: Recruiting

Location contact

Macy Stahl

CONTACT

[email protected]

434-924-1655

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Post-menopausal female (greater than age 45 but less than age 75)
  • Sedentary (does not exercise regularly or less than 2 bouts of exercise per week)
  • No major changes in medication in the last 3 months

Exclusion criteria

  • Smokers within last 5 years
  • Weight unstable (loss/gain of more than 3kg in the past 3 months)
  • Any medical condition that prevents the subject from exercising safely
  • Hormone replacement therapy (current or within last 3 months)
  • Diabetes
  • Currently or recently on vasoactive medications (i.e., calcium channel blockers, statins, ACE or renin inhibitors, ARBs, nitrates, alpha- or beta-blockers, diuretics, proton pump inhibitors, etc.)
  • Oral antibiotic use within previous four weeks
  • Oral disease or poor oral health as determined by the Oral Health Questionnaire
  • Using an antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use

Treatment and study plan

Nitrate-rich beetroot Juice

Dietary Supplement

subjects will consume 1 bottle of nitrate-rich beetroot juice (~400mg of nitrate each) 2x a day

Other names: Inorganic Nitrate, James White Beet It

High intensity exercise

Behavioral

exercise at an intensity midway between the lactate threshold and VO2peak, from the screening test at an RPE of ~ 15-17

Moderate Intensity Exercise

Behavioral

exercise at the RPE at LT associated an ~ RPE of 10-12

Nitrate-Depleted Placebo Beetroot Juice

Dietary Supplement

Subjects will consume 1 bottle of nitrate-depleted beetroot juice 2x a day

Primary outcomes

  1. Vascular Endothelial Function (Flow-Mediated Dilation [FMD])

    Time frame: Baseline and after 1-month of exercise training

    Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The arteries will be imaged using a high-resolution 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 3 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle.

  2. Cardiorespiratory Fitness

    Time frame: Baseline and after 1-month of exercise training

    Peak aerobic capacity (VO2peak) will be assessed using a symptom-limited graded exercise test on a treadmill. An IV will be placed and lactate measured during rest and after the completion of every 3-minute stage to determine lactate threshold at VO2peak.

Secondary outcomes

  1. Oral Nitrate Reducing Capacity

    Time frame: Baseline and after 1-month of exercise training

    Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through an unstimulated saliva sample and a rinse of a standard nitrate solution.

  2. Skeletal muscle perfusion

    Time frame: Baseline and after 1-month of exercise training

    Skeletal Muscle Blood Flow (straight gauge plethysmography) will be measured non-invasively using venous occlusion/strain-gauge plethysmography both at rest and during reactive hyperemia following 5-minutes of occlusion via the Hokanson A16. A strain gauge device will be place around the widest part of the participant's right calf. A blood pressure place around participant's ankle will be inflated for 60 seconds to eliminate foot circulation from the measurement. At the same time, a cuff placed on the thigh will be inflated to block venous blood flow. The cuff occlusion will be held for ~60 seconds ((several cardiac cycles (4-6 cycles)) to obtain resting blood flow measurements.

  3. Peripheral and Central Blood Pressures

    Time frame: Baseline and after 1-month of exercise training

    Brachial artery blood pressures will be obtained using a standard sphygmomanometer. Aortic blood pressures will be obtained using applanation tonometry (SphygmoCor version 8.0, AtCor Medical).

  4. 24-hour ambulatory blood pressure

    Time frame: Baseline and after 1-month of exercise training

    Blood pressure will be monitored using a standard ambulatory brachial artery blood pressure cuff (SunTech Oscar 2, SunTech Medical). Blood pressure measurements are programmed to be taken every 30-minutes during the day and every hour at night. This allows for monitoring of nighttime blood pressure changes and variations throughout the day.

  5. Skeletal muscle microvascular perfusion (near-infra-red- spectroscopy)

    Time frame: Baseline and after 1-month of exercise training

    Tissue oxygenation will be captured noninvasively using non-invasive, near-infrared spectrometry (NIRS, PortaMon, Artinis Medical Systems B.V., The Netherlands) positioned on the gastrocnemius or vastus lateralis muscle.

  6. Lipids

    Time frame: Baseline

    A blood sample will be obtained to measure lipids.

  7. Hemoglobin

    Time frame: Baseline and after 1-month of exercise training

    A blood sample will be obtained to measure hemoglobin.

  8. Plasma Nitrate

    Time frame: Baseline and after 1-month of exercise training

    A fasting blood draw will be taken. Following the blood draw, the participant will take one dose of Beetroot juice. The participant will then return to the lab three hours later for a second blood draw to assess level of nitrate in the plasma.

  9. Plasma Nitrite

    Time frame: Baseline and after 1-month of exercise training

    A fasting blood draw will be taken. Following the blood draw, the participant will take one dose of Beetroot juice. The participant will then return to the lab three hours later for a second blood draw to assess level of nitrite in the plasma.

Study contacts

Contact information is provided by the study sponsor or research team.

Macy Stahl

CONTACT

[email protected]

434-924-1655

Sponsors and collaborators

Lead sponsor

University of Virginia

Other

Registry information

Official study title

Effects of Exercise Training Intensity and Inorganic Nitrate Supplementation on Vascular Health and Fitness in Post-Menopausal Females

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jun 28, 2024
Registry last updated
Jul 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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