BEETroot Juice to Reverse Functional Impairment in PAD

The BEET PAD Trial is a multi-centered double-blind randomized clinical trial designed to determine whether beetroot juice, compared to placebo, improves six-minute walk distance at four month follow-up in people with lower extremity peripheral artery disease (PAD). Investigators hypothesize that by simultaneously increasing lower extremity perfusion, gastrocnemius muscle mitochondrial activity, and myofiber health and regeneration, beetroot juice will significantly improve walking performance in people with PAD. The primary aim is to determine whether beetroot juice significantly improves six-minute walk distance at 4-month follow-up in people with PAD, compared to placebo. Preliminary evidence suggests that beetroot juice has both acute and chronic effects on walking performance in PAD. The primary outcome will measure the combined acute and chronic effect of beetroot juice (i.e. the maximal effect) on change in 6-minute walk at 4-month follow-up. In secondary aims, investigators will distinguish between acute and chronic effects of beetroot juice on six-minute walk and delineate biologic pathways by which beetroot juice improves walking performance in PAD, by measuring change in gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health. The trial will assess the durability of beetroot juice effects on six-minute walk. Nitrate in beetroot juice is metabolized to nitrite and subsequently to NO, attaining peak nitrite levels 2.5 hours after ingestion. The trial will determine whether a higher peak or a greater increase in plasma nitrite at 2.5 hours after beetroot juice consumption at baseline has a greater effect on six-minute walk at 4-month follow-up, compared to a lower peak or a smaller increase, respectively.

Inclusion Criteria:Age 50 and olderPresence of peripheral artery disease, defined as:An ankle brachial index (ABI) <= 0.90 at baselineVascular lab evidence of PAD (such as a toe brachial pressure <= 0.70 or an ankle brachial index <=0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.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:Above- or below-knee amputationCritical limb ischemia defined as an ABI <0.30 or <0.40 with symptoms of rest painWheelchair confinement or requiring a walker to ambulateWalking is limited by a symptom other than PADCurrent foot ulcer on bottom of footFailure to successfully complete the study run-inPlanned major surgery, coronary or leg revascularization during the next five monthsMajor surgery, coronary or leg revascularization or major cardiovascular event in the previous three monthsMajor 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.]Mini-Mental Status Examination (MMSE) score < 23Allergy to beetroot juiceCurrently consuming beetroot juice or oral nitrate or nitrite and/or unwilling to avoid beetroot juice during the study.Non-English speakingParticipation 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.]Visual impairment that limits walking ability.Six-minute walk distance of <500 feet or >1600 feet.Baseline blood pressure <100/50.Participation in a supervised treadmill exercise program in previous three months.Using an antibacterial mouthwash (such as Cepacol) or a mouthwash containing chlorhexidine and unwilling to discontinue.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.