Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. Walking exercise is first line therapy to improve walking distance for PAD, but it does not eliminate ischemic leg symptoms in most people with PAD. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. Participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. As of 2018, only 1.3% of patients with Medicare and symptomatic PAD had enrolled in SET. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. In 2021, the investigators reported that a home-based exercise intervention that incorporated behavioral methods significantly improved six-minute walk in PAD, compared to an attention control group. But no randomized trials have compared SET to a home-based exercise intervention that incorporated behavioral change methods in PAD. However, 45% of people with PAD do not meaningfully respond to exercise interventions, defined as failure to improve six-minute walk by \> 20 meters. This phenomenon occurs for both supervised and home-based exercise. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. Therefore, the investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
210
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 is a 12 week intervention where participants will walk at home for exercise with guidance from a study coach. They will have 4 in person visits in the first four weeks and then have weekly phone calls in the last 8 weeks of the intervention with their coach.
Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
RECRUITINGUniversity of Chicago
Chicago, Illinois, United States
RECRUITINGUniversity of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGSix-Minute Walk Distance
Change in six-minute walk distance
Time frame: Measured at baseline and 12 week follow-up
Walking Impairment Questionnaire (WIQ) Distance Score
WIQ distance score - Range 0-100, 100 is best.
Time frame: measured at baseline and 12 weeks
PROMIS Mobility Questionnaire Score
PROMIS mobility score from administered PROMIS questionnaire. Score range is from zero to infinity and a higher score means a better outcome.
Time frame: measured at baseline and 12 weeks
20-meter Improvement in Six-Minute Walk Distance
Meaningful response to exercise interventions
Time frame: measured at 12 weeks
Step Count
Step count measured over seven days with the FITBIT
Time frame: measured at baseline and 12 weeks
Six-Minute Walk Distance
Change in six-minute walk distance
Time frame: Measured at baseline and 24-week follow up
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