RESIST PAD is a randomized trial of 200 PAD patients to establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.
Walking exercise is the only highly effective medical therapy for improving walking impairment in people disabled by lower extremity peripheral artery disease (PAD). However, approximately 45% of people with PAD do not meaningfully improve after an exercise intervention. Biologic pathways that mediate exercise response and biologic pathways that explain exercise non-response in PAD are unknown. Based on preliminary evidence, it is hypothesized that in PAD, exercise-induced arterial shear stress stimulates nitric oxide synthase (NOS) activity to increase nitric oxide bioavailability and improve leg perfusion, skeletal muscle mitochondrial activity, and walking ability. It is further hypothesized that exercise increases plasma nitric oxide during exercise in "responders" but does not meaningfully increase nitric oxide during exercise in "non-responders". RESIST PAD is a randomized trial of 200 PAD patients that will establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
200
This is a 12 week intervention where participants will walk for exercise 3 times a week on a treadmill at a center while being supervised by healthcare personnel.
This group will attend weekly one-hour educational sessions either on Zoom or in-person for 12 weeks. These sessions are on topics of interest to the typical PAD patient and may be led by study staff, physicians, or other health care workers.
Participants randomized to this group will drink nitrate-rich beetroot juice while engaged in supervised exercise.
Participants randomized to this group will drink placebo while engaged in supervised exercise.
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
RECRUITINGUniversity of Chicago
Chicago, Illinois, United States
NOT_YET_RECRUITINGDelta nitrite
Change in plasma nitrite from the beginning to the end of a maximal exercise stress test
Time frame: Baseline to 12-week follow-up
Six-minute walk
Change in six-minute walk distance
Time frame: From 12-weeks to 24-week follow-up
Calf muscle perfusion
Change in calf muscle perfusion, measured with arterial spin labeling MRI
Time frame: Baseline to 12-week follow-up
Calf muscle perfusion
Change in calf muscle perfusion, measured with arterial spin labeling MRI
Time frame: From 12-weeks to 24-week follow-up
Brachial artery flow-mediated dilation (FMD)
Change in brachial artery diameter in response to post-cuff occlusion hyperemia
Time frame: Baseline to 12-week follow-up
Brachial artery flow-mediated dilation (FMD)
Change in brachial artery diameter in response to post-cuff occlusion hyperemia
Time frame: From 12 weeks to 24-week follow-up
Delta nitrite
Change in plasma nitrite between the beginning and end of an exercise stress test.
Time frame: From 12 weeks to 24-week follow-up
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