Dietary Nitrate and Exercise to Augment Exercise Training Benefits in Subjects With DM+PAD

Phase 2

Completed

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

Brief Summary: The hypothesis of this proposal is that in subjects with Type II diabetes mellitus (T2D) and peripheral arterial disease (PAD) with intermittent claudication (IC), 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 claudication onset time \[COT\] and peak walking time \[PWT\] relative to a group with the same exercise training but supplemented with placebo .This study is essentially exploratory in nature and designed to provide us with information to adequately develop power and execute a larger study. We have previously seen benefits from nitrate supplementation on function in PAD.

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) & Supervised Exercise Training	Beetroot Juice (Beet-It Stamina Shot) and 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 - Maximal Oxygen Capacity (VO2peak)	Baseline & 16 Weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption
Change in Exercise Capacity - Time to Exhaustion (TTE)	Baseline & 16 Weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Time to Exhaustion (TTE)
Change in Exercise Capacity - Claudication Onset Time (COT)	Baseline & 16 Weeks	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Claudication Onset Time (COT)

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 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.
Change In Vascular Function	Baseline and 16 weeks	Vascular Function will be measured as the Brachial artery flow-mediated dilation (BAFMD)

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