Dietary Nitrates and Vascular Function in Patients With Peripheral Artery Disease

Study Overview
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Brief Summary
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The overarching question addressed in the current project is: Does dietary nitrate supplementation (8 weeks) improve physiological function in patients with peripheral arterial disease (PAD)? The investigators will specifically address whether dietary nitrate supplementation enhances blood vessel function, blood pressure regulation, and exercise capacity. The proposed project uses an array of clearly defined measurements which will allow investigators to quantify blood vessel function (vasodilator responsiveness and arterial stiffness), blood pressure (variability and responsiveness to stress), and functional capacity before and after 8 weeks of dietary supplementation.

Official Title
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Dietary Nitrates and Vascular Function in Patients With Peripheral Artery Disease

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Dietary Supplement: Sodium Nitrate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented peripheral artery disease Ankle-Brachial Index (ABI) < or = to 0.90 Exclusion Criteria: Non-atherosclerotic vascular disease Critical limb ischemia Active ischemic ulceration Recent (within one year) revascularization Symptomatic coronary artery disease (angina pectoris) Heart failure Resting systolic blood pressure > 180 mmHg or diastolic pressure > 100 mmHg Hypotension (resting systolic BP < 90 mmHg) Smoking or history of smoking within past one year Use of phosphodiesterase V inhibitor drugs Women with history of hormone replacement therapy within the past 6 months

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Nitrate<br>Sodium Nitrate (1g/day) for 8 weeks | Dietary Supplement: Sodium Nitrate<br>* Sodium Nitrate (1g/day) for 8 weeks<br>|
| Placebo Comparator: Placebo capsule<br>Microcrystalline cellulose (daily) for 8 weeks | Other: Placebo<br>* Microcrystalline cellulose (daily) for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vasodilator Capacity | Forearm and calf blood flow will be measured independently by venous occlusion plethysmography using mercury-in-silastic strain gauges. Plethysmographic measurements will be made at rest and following 5 minutes of ischemia (reactive hyperemia) of the distal limb (forearm and calf). Peak blood flow will be determined as the highest flow recorded during the post deflation period. Total blood flow will be measured as the area under the time-curve after resting flow is subtracted. Vascular conductance will be calculated using blood flow/mean arterial pressure (via finger plethysmograph). | Pre and post 8 weeks of dietary nitrate supplementation | 
| Change in Arterial Stiffness | ECG gated arterial waveforms will be obtained via applanation tonometry from the carotid and femoral arteries. The pulse wave velocity (PWV; index of arterial stiffness) will be determined between the carotid and femoral measurement sites (cfPWV). The time (t) between the feet of recorded pressure waves will be determined as the mean of 10 consecutive cardiac cycles. PWV is calculated from the distance (D; meters) between measurement points and the measured time delay (t): PWV = D/Δt (m/s). | Pre and post 8 weeks of dietary nitrate supplementation | 
| Change in Functional Capacity - Distance Walked in 6 Minutes | 6-minute walk tests will be performed before and after treatment to assess functional capacity. The main comparisons will be changes distance walked in 6 minutes after 8 weeks of dietary nitrate supplementation. | Pre and post 8 weeks of dietary nitrate supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nitrates, blood flow, vascular function, exercise