Exercise Training Intensity and Nitrate Supplementation in Post-Menopausal Females
NCT Number: NCT06480695
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Menopause
Interventions: DIETARY_SUPPLEMENT: Berkeley Life Pro Nitrate Capsules|BEHAVIORAL: High Intensity Exercise|BEHAVIORAL: Moderate Intensity Exercise
Sponsor: University of Virginia
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2024-07-01
Completion Date: 2025-06-30

Summary:
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 tablets, or tablets 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.

Primary Outcome Measures: Vascular Endothelial Function (Flow-Mediated Dilation [FMD]), 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., Baseline and after 1-month of exercise training|Cardiorespiratory Fitness, 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., Baseline and after 1-month of exercise training
Secondary Outcome Measures: Oral Nitrate Reducing Capacity, Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through a swab on the dorsal surface of the tongue, an unstimulated saliva sample, and a rinse of a standard nitrate solution., Baseline and after 1-month of exercise training|Skeletal muscle perfusion, 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., Baseline and after 1-month of exercise training|Peripheral and Central Blood Pressures, 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)., Baseline and after 1-month of exercise training|24-hour ambulatory blood pressure, 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., Baseline and after 1-month of exercise training|Skeletal muscle microvascular perfusion (near-infra-red- spectroscopy), 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., Baseline and after 1-month of exercise training|Lipids, A blood sample will be obtained to measure lipids., Baseline and after 1-month of exercise training|Hemoglobin, A blood sample will be obtained to measure hemoglobin., Baseline and after 1-month of exercise training|Plasma Nitrate, 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., Baseline and after 1-month of exercise training|Plasma Nitrite, 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., Baseline and after 1-month of exercise training