Actively Recruiting

Phase 3
Age: 50Years +
All Genders
NCT06032065

SMART Exercise for PAD

Led by Northwestern University · Updated on 2026-04-15

210

Participants Needed

3

Research Sites

290 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

SMART Exercise for PAD

Who Can Participate

Age: 50Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 50 years or older
  • Diagnosis of peripheral artery disease (PAD) defined by one of the following: ankle brachial index (ABI) ≤ 0.90 at baseline; vascular lab evidence of PAD such as toe brachial pressure ≤ 0.70 or ABI ≤ 0.90; angiographic evidence showing at least 70% artery narrowing in the lower limbs; or ABI > 0.90 and < 1.00 with a 20% or greater drop after heel-rise test
Not Eligible

You will not qualify if you...

  • Above- or below-knee amputation
  • Limb-threatening ischemia with ABI < 0.40 and rest pain
  • Confined to wheelchair or require a walker to walk
  • Walking limitations due to conditions other than PAD
  • Current foot ulcer on the bottom of the foot
  • Unwillingness to drink beetroot juice
  • Unwillingness to accept randomization to exercise groups
  • Planning new walking exercise outside the study or unwilling to avoid such exercise during the trial
  • Already exercising at levels similar to the study interventions
  • End-stage kidney disease requiring dialysis
  • Planned major surgery or revascularization in next six months
  • Major surgery, revascularization, or cardiovascular event in past three months
  • Major illnesses including lung disease needing oxygen, Parkinson's disease, life-threatening illness with less than six months expected survival, or cancer needing treatment in past two years (except early stage cancer with excellent prognosis)
  • Mini-Mental Status Exam (MMSE) score less than 23 unless due to language or education factors
  • Allergy to beetroot juice
  • Currently consuming beetroot juice, oral nitrate/nitrite, or beetroot supplements and unwilling to stop
  • Unstable angina
  • Abnormal stress test without physician clearance for exercise
  • Non-English speaking
  • Participation in another clinical trial in previous three months with specific timing restrictions
  • Visual impairment limiting walking ability
  • Baseline blood pressure less than 100/45
  • Participation in supervised treadmill or cardiac rehab programs in past three months
  • Use of bactericidal mouthwash and unwilling to stop
  • Estimated glomerular filtration rate (eGFR) less than 30 or potassium level above 5.0
  • History of kidney stones requiring low oxalate intake
  • Investigator discretion if trial is unsafe or unsuitable

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 3 locations

1

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

Actively Recruiting

2

University of Chicago

Chicago, Illinois, United States, 60637

Actively Recruiting

3

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Actively Recruiting

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Research Team

M

Mary McDermott, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

FACTORIAL

Primary Purpose

TREATMENT

Number of Arms

4

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