Effects of Inorganic Nitrate and Intensity of Exercise on Cardiovascular Health in Post-Menopausal Females

NCT05221905 | Completed Phase 1 FDA Drug

• 1 other identifier: HSR210326
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Post-menopausal females experience elevated cardiovascular disease risk (CVD), compared to premenopausal females and age-matched males. Current exercise guidelines appear inadequate to ameliorate this increased risk and higher intensity exercise may be necessary. Oral inorganic nitrate supplementation enhances both exercise performance and CVD risk profile in several clinical conditions. However, the effects of this intervention in post-menopausal females is unexplored.

Conditions

Vascular Dilation; Arterial Stiffness

Keywords

Flow-mediated dilation; Pulse wave velocity; Exercise intensity; Vascular function

Outcome Measures

Primary Outcomes (6)

• Baseline Flow-Mediated Dilation

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  Baseline (minute 0).

• Post-Exercise/Control Flow-Mediated Dilation (60 minutes)

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  60 minutes post-baseline.

• Post-Exercise/Control Flow-Mediated Dilation (90 minutes)

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  90 minutes post-baseline.

• Post-Exercise/Control Flow-Mediated Dilation (120 minutes)

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  120 minutes post-baseline.

• Post-Exercise/Control Flow-Mediated Dilation (150 min)

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  150 minutes post-baseline.

• Post-Exercise/Control Flow-Mediated Dilation (180 min)

  Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution doppler ultrasound utilizing a 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle. Images will be analyzed offline using specialized software (Medical Imaging Applications, Inc.) to calculate the change in brachial artery diameter.

  180 minutes post-baseline.

Secondary Outcomes (6)

• Baseline Pulse Wave Velocity

  Baseline (minute 0).

• Post-Exercise/Control Pulse Wave Velocity (60 min)

  60 minutes post-baseline.

• Post-Exercise/Control Pulse Wave Velocity (90 min)

  90 minutes post-baseline.

• Post-Exercise/Control Pulse Wave Velocity (120 min)

  120 minutes post-baseline.

• Post-Exercise/Control Pulse Wave Velocity (150 min)

  150 minutes post-baseline.

Study Arms (3)

Acute High-Intensity Exercise

ACTIVE COMPARATOR

Subjects will exercise at an intensity of 75% of the difference between the lactate threshold and VO2peak until 200 kcal are expended. Pre- and post-testing measures of vascular health will be completed at baseline (0 min) and again 60, 90, 120, 150, 180 min post-baseline testing, with exercise taking place during time points 0-60 min.

Drug: BEET IT - Concentrate Beet root juice; Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)

Acute Moderate-Intensity Exercise

ACTIVE COMPARATOR

Subjects will exercise at an intensity at the lactate threshold until 200 kcal are expended. Pre- and post-testing measures of vascular health will be completed at baseline (0 min) and again 60, 90, 120, 150, 180 min post-baseline testing, with exercise taking place during time points 0-60 min.

Drug: BEET IT - Concentrate Beet root juice; Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)

Non-Exercise Control

PLACEBO COMPARATOR

Measures of vascular health will be completed at baseline (0 min) and again 60, 90, 120, 150, 180 min post-baseline testing, without exercise taking place during time points 0-60 min.

Drug: BEET IT - Concentrate Beet root juice; Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)

Interventions

BEET IT - Concentrate Beet root juice DRUG

Beet It Sport (James White Drinks, Ltd.) each containing 400mg of inorganic nitrate (\~6.5 mmol) will be consumed twice daily (totalling \~13 mmol of inorganic nitrate per day) for at least 2 days prior to testing visits, as well as 2 hours prior to testing visits.

Also known as: Dietary Nitrate supplementation (nitrate rich)

Acute High-Intensity Exercise; Acute Moderate-Intensity Exercise; Non-Exercise Control

BEET IT - Concentrate Beet root juice (nitrate depleted) DRUG

Beet It Sport (James White Drinks, Ltd.) each containing 0mg of inorganic nitrate (\~0 mmol) will be consumed twice daily (totalling \~0 mmol of inorganic nitrate per day) for at least 2 days prior to testing visits, as well as 2 hours prior to testing visits. It is provided by the same company that produces the concentrated beet root juice shots (James White Drinks) but the placebo version is nitrate-depleted.

Also known as: Dietary Nitrate supplementation (nitrate depleted)

Acute High-Intensity Exercise; Acute Moderate-Intensity Exercise; Non-Exercise Control

Eligibility Criteria

• Age: 45 Years - 75 Years
• Gender Eligibility Details: All subjects are post-menopausal females.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Post-menopausal female, defined as having not had a menstrual cycle for at least 1 year
• Greater than age 45 but less than age 75
• Sedentary (does not exercise regularly)
• 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)
• 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.)
• Hysterectomy or oophorectomy

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

Student Health and Wellness Center

Charlottesville, Virginia, 22902, United States

Location

Study Officials

• Arthur Weltman, PhD

  Professor of Kinesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study, where neither the investigators nor the subjects will know whether the participants are receiving the active supplement or placebo supplement until study conclusion.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Subject are stratified randomized to consume either beetroot juice with, or without, inorganic nitrate and will consume this same supplement throughout all testing

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: February 3, 2022
• Study Start: November 1, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified data will be shared upon reasonable request for 3 years after study completion
• Access Criteria: Email Austin Hogwood at ach2jb@virginia.edu for any requests.

Locations

US (1)