Exercise Training Intensity and Nitrate Supplementation in Post-Menopausal Females

NCT06480695 | Recruiting

• 1 other identifier: HSR231665
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Menopause

Keywords

Inorganic Nitrate; Menopause; High Intensity Exercise; Vascular Health

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Oral Nitrate Reducing Capacity

  Baseline and after 1-month of exercise training

• Skeletal muscle perfusion

  Baseline and after 1-month of exercise training

• Peripheral and Central Blood Pressures

  Baseline and after 1-month of exercise training

• 24-hour ambulatory blood pressure

  Baseline and after 1-month of exercise training

• Skeletal muscle microvascular perfusion (near-infra-red- spectroscopy)

  Baseline and after 1-month of exercise training

Study Arms (4)

Nitrate-Rich Beetroot Juice + High Intensity Exercise (HIE)

EXPERIMENTAL

Participants assigned to this group will be instructed to consume 1 bottle of nitrate-rich beetroot juice (\~400mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 15-17 based on the participant's VO2peak test.

Dietary Supplement: Nitrate-Rich Beetroot Juice; Behavioral: High Intensity Exercise

Nitrate-Depleted Placebo Beetroot Juice + High Intensity Exercise (HIE)

PLACEBO COMPARATOR

Participants assigned to this group will be instructed to consume 1 bottle of nitrate-depleted beetroot juice 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 15-17 based on the participant's VO2peak test.

Behavioral: High Intensity Exercise; Dietary Supplement: Nitrate-Depleted Placebo Beetroot Juice

Nitrate-Rich Beetroot Juice + Moderate Intensity Exercise (MIE)

ACTIVE COMPARATOR

Participants assigned to this group will be instructed to consume 1 bottle of nitrate-rich beetroot juice (\~400mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 10-12 based on the participant's VO2peak test.

Dietary Supplement: Nitrate-Rich Beetroot Juice; Behavioral: Moderate Intensity Exercise

Nitrate-Depleted Placebo Beetroot Juice + Moderate Intensity Exercise (MIE)

PLACEBO COMPARATOR

Participants assigned to this group will be instructed to consume 1 bottle of nitrate-depleted beetroot juice 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 10-12 based on the participant's VO2peak test.

Behavioral: Moderate Intensity Exercise; Dietary Supplement: Nitrate-Depleted Placebo Beetroot Juice

Interventions

Nitrate-Rich Beetroot Juice DIETARY_SUPPLEMENT

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

Also known as: Inorganic Nitrate, James White Beet It

Nitrate-Rich Beetroot Juice + High Intensity Exercise (HIE); Nitrate-Rich Beetroot Juice + Moderate Intensity Exercise (MIE)

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

Nitrate-Depleted Placebo Beetroot Juice + High Intensity Exercise (HIE); Nitrate-Rich Beetroot Juice + High Intensity Exercise (HIE)

Moderate Intensity Exercise BEHAVIORAL

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

Nitrate-Depleted Placebo Beetroot Juice + Moderate Intensity Exercise (MIE); Nitrate-Rich Beetroot Juice + Moderate Intensity Exercise (MIE)

Nitrate-Depleted Placebo Beetroot Juice DIETARY_SUPPLEMENT

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

Nitrate-Depleted Placebo Beetroot Juice + High Intensity Exercise (HIE); Nitrate-Depleted Placebo Beetroot Juice + Moderate Intensity Exercise (MIE)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

Student Health and Wellness Building - Department of Kinesiology

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Interventions

High-Intensity Interval Training

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Jason Allen, PhD

  UVA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Casey Derella, PhD

CONTACT

434-924-1655; bxg7vn@uvahealth.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A study team member not associated with the trial will perform the randomization scheme for the supplementation. Exercise groups will not be blinded but data will not be analyzed until the end or re-labeled by another team member so assessors are unaware while analyzing the data.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Subjects will be randomized to one-month of either high or moderate aerobic exercise training and then further randomized to nitrate or placebo.

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 28, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)