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

Study Overview
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Brief Summary
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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.

Detailed Description
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The purpose of this study is to determine whether acute inorganic nitrate supplementation and exercising at different exercise intensities (high vs moderate) improve vascular health in post-menopausal females.

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

Conditions
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Vascular Dilation, Arterial Stiffness

Intervention / Treatment
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* Drug: BEET IT - Concentrate Beet root juice
* Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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) 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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subject are stratified randomized to consume either beetroot juice with, or without, inorganic nitrate and will consume this same supplement throughout all testing
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acute High-Intensity Exercise<br>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<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate rich);Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate depleted);|
| Active Comparator: Acute Moderate-Intensity Exercise<br>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<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate rich);Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate depleted);|
| Placebo Comparator: Non-Exercise Control<br>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<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate rich);Drug: BEET IT - Concentrate Beet root juice (nitrate depleted)<br>* 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.<br>* Other names: Dietary Nitrate supplementation (nitrate depleted);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Pulse Wave Velocity | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | Baseline (minute 0). | 
| Post-Exercise/Control Pulse Wave Velocity (60 min) | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | 60 minutes post-baseline. | 
| Post-Exercise/Control Pulse Wave Velocity (90 min) | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | 90 minutes post-baseline. | 
| Post-Exercise/Control Pulse Wave Velocity (120 min) | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | 120 minutes post-baseline. | 
| Post-Exercise/Control Pulse Wave Velocity (150 min) | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | 150 minutes post-baseline. | 
| Post-Exercise/Control Pulse Wave Velocity (180 min) | Supine measures of carotid to femoral pulse wave velocity will be measured using a SphygmoCor Xcel device. | 180 minutes post-baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular function, Flow-mediated dilation, Pulse wave velocity, Exercise intensity