Overview

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.

Eligibility

Inclusion Criteria:

        First, all participants will be age 50 and older. Second, all participants will have PAD.
        PAD will be defined as either:
          1. An ABI <= 0.90 at baseline.
          2. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to
             0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence
             of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.
          3. An ABI of >0.90 and <1.00 who experience a 20% or greater drop in ABI in either leg
             after the heel-rise test.
        Exclusion Criteria:
          1. Above- or below-knee amputation
          2. Limb-threatening ischemia defined as an ABI <0.40 with symptoms of rest pain
          3. Wheelchair confinement or requiring a walker to ambulate
          4. Walking is limited by a condition other than PAD
          5. Current foot ulcer on bottom of foot
          6. Unwilling to drink beetroot juice
          7. Unwilling to accept randomization into either group (home based exercise or supervised
             exercise)
          8. Planning to engage in new walking exercise outside of the study or unwilling to
             refrain from new walking exercise activity during the trial.
          9. Already exercising at a level consistent with exercise intervention.
         10. End-stage kidney disease (ESKD) associated with the need for dialysis.
         11. Planned major surgery, coronary or leg revascularization during the next six months
         12. Major surgery, coronary or leg revascularization or major cardiovascular event in the
             previous three months
         13. Major medical illness including lung disease requiring oxygen, Parkinson's disease, a
             life-threatening illness with life expectancy less than six months, or cancer
             requiring treatment in the previous two years. [NOTE: potential participants may still
             qualify if they have had treatment for an early stage cancer in the past two years and
             the prognosis is excellent. Participants who require oxygen only at night may still
             qualify.]
         14. Mini-Mental Status Examination (MMSE) score < 23 or dementia. However, if the MMSE is
             < 23 and the Principal Investigator evaluation determines that the lower score is
             related to language barriers or education level, the Principal Investigator has
             discretion to allow a participant with MMSE < 23 to participate, as appropriate.
         15. Allergy to beetroot juice
         16. Currently consuming beetroot juice or oral nitrate or nitrite, or a beetroot
             supplement, and/or unwilling to avoid these during study participation. Participants
             currently consuming one cup of beets daily will be asked to discontinue beet ingestion
             for 30 days before baseline testing and throughout the clinical trial. If the
             potential participant is unwilling to refrain from daily beet consumption of one cup
             or more, they will not be eligible for the clinical trial.
         17. Unstable angina
         18. Abnormal baseline stress test without subsequent clearance for exercise by physician
         19. Non-English speaking. The SMART PAD interventions are delivered by interventionists
             who do not speak non-English languages. The integrity of the clinical trial requires
             clear and effective communication for data collection and intervention delivery. The
             trial does not have staff members who are fluent in non-English languages, nor does it
             have the ability to translate all study materials into other languages.
         20. Participation in or completion of a clinical trial in the previous three months.
             [NOTE: after completing a stem cell or gene therapy intervention, participants will
             become eligible after the final study follow-up visit of the stem cell or gene therapy
             study so long as at least six months have passed since the final intervention
             administration. After completing a supplement or drug therapy (other than stem cell or
             gene therapy), participants will be eligible after the final study follow-up visit as
             long as at least three months have passed since the final intervention of the trial.]
             Participants in a study that involved up to three single doses of nitrate-rich
             beetroot juice administered on separate days may participate if a month has passed
             since their last dose of nitrate-rich beetroot juice.
         21. Visual impairment that limits walking ability.
         22. Baseline blood pressure <100/45.
         23. Participation in a supervised treadmill exercise program or cardiac rehabilitation
             program in previous three months.
         24. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash
             determined to be bactericidal and unwilling to discontinue.
         25. In addition to the above criteria, investigator discretion will be used to determine
             if the trial is unsafe or not a good fit for the potential participant.