Nitrites, Exercise, and Peripheral Arterial Disease

Phase 2

Completed

Interventions: Drug: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training
Other: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training

Brief Summary: The hypothesis of this proposal is that in subjects with PAD, regular consumption of a high nitrate supplement which raises plasma nitrite, in conjunction with 12 weeks of supervised exercise training at the limb ischemic threshold (SET) will produce a greater clinical benefit (increases in COT and PWT) than placebo plus supervised exercise at the limb ischemic threshold (PET).

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Individuals with known alcohol or drug abuse problems
Individuals who have suffered a heart attack or stroke, or have changes on a resting ECG, in the last 3 months
Those classified as American Heart Association Class D
Gangrene, impending limb loss or osteomyelitis
Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment
Severe peripheral neuropathy
Any condition other than PAD that limits walking
Chest pain during treadmill exercise which appears before the onset of claudication, or >3mm ST depression during exercise
Subjects taking nitrates or nitroglycerin products
Must not be taking protein pump inhibitor medications

Arm && Interventions

Group	Intervention	Description
BR Juice (Beet-It Stamina Shot) and Exercise Training	Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training	Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 \& 2) and at the end of the trial (between Visits 3 \& 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 \& 3) to when the subject has not consumed the beverage (Visits 1 \& 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 \& 3 and for all supervised exercise training visits during the 12 week intervention.
BR Juice Placebo and Exercise Training	Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training	Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 \& 2) and at the end of the trial (between Visits 3 \& 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 \& 3) to when the subject has not consumed the beverage (Visits 1 \& 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 \& 3 and for all supervised exercise training visits during the 12 week intervention.

Primary Outcome Measures

Name	Time	Method
Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)	Baseline and 16 Weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.
Change In Time To Exhaustion	Baseline and 16 weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.

Secondary Outcome Measures

Name	Time	Method
Change in Functional Ability	Baseline and 16 Weeks	Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.
Change In Claudication Onset Time	Baseline and 16 weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.
Change In Vascular Function (BAFMD)	Baseline and 16 weeks	Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .
Change in Angiogenesis	Baseline and 16 weeks	Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups

Locations (1): Duke Diet & Fitness Center
🇺🇸
Durham, North Carolina, United States