SMART Exercise for PAD

NCT06032065 | Recruiting Phase 3 DMC

• 1 other identifier: STU00218112
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 3

Brief Summary

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

Peripheral Arterial Disease; Aging; Peripheral Vascular Diseases; Walking, Difficulty

Keywords

behavior change; patient reported outcome measure

Outcome Measures

Primary Outcomes (1)

• Six-Minute Walk Distance

  Change in six-minute walk distance

  Measured at baseline and 12 week follow-up

Secondary Outcomes (5)

• Walking Impairment Questionnaire (WIQ) Distance Score

  measured at baseline and 12 weeks

• PROMIS Mobility Questionnaire Score

  measured at baseline and 12 weeks

• 20-meter Improvement in Six-Minute Walk Distance

  measured at 12 weeks

• Step Count

  measured at baseline and 12 weeks

• Six-Minute Walk Distance

  Measured at baseline and 24-week follow up

Other Outcomes (9)

• Physical Activity Step Count

  Measured at baseline and 24 weeks

• Physical activity distance

  Measured at baseline and 24 weeks.

• Short physical performance battery (SPPB)

  measured at baseline and 12 weeks

Study Arms (4)

Supervised treadmill exercise + nitrate rich beetroot juice

EXPERIMENTAL

This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.

Behavioral: Supervised Treadmill Exercise; Dietary Supplement: Nitrate-rich beetroot Juice

Supervised treadmill exercise + placebo

PLACEBO COMPARATOR

This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.

Behavioral: Supervised Treadmill Exercise

Home-based walking exercise + nitrate rich beetroot juice

EXPERIMENTAL

This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.

Behavioral: Home-Based Exercise; Dietary Supplement: Nitrate-rich beetroot Juice

Home-based walking exercise + placebo

PLACEBO COMPARATOR

This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks.

Behavioral: Home-Based Exercise

Interventions

Supervised Treadmill Exercise BEHAVIORAL

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.

Supervised treadmill exercise + nitrate rich beetroot juice; Supervised treadmill exercise + placebo

Home-Based Exercise BEHAVIORAL

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.

Home-based walking exercise + nitrate rich beetroot juice; Home-based walking exercise + placebo

Nitrate-rich beetroot Juice DIETARY_SUPPLEMENT

Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.

Home-based walking exercise + nitrate rich beetroot juice; Supervised treadmill exercise + nitrate rich beetroot juice

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as either:
• An ABI \<= 0.90 at baseline.
• 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.
• 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.

You may not qualify if:

• Above- or below-knee amputation
• Limb-threatening ischemia defined as an ABI \<0.40 with symptoms of rest pain
• Wheelchair confinement or requiring a walker to ambulate
• Walking is limited by a condition other than PAD
• Current foot ulcer on bottom of foot
• Unwilling to drink beetroot juice
• Unwilling to accept randomization into either group (home based exercise or supervised exercise)
• Planning to engage in new walking exercise outside of the study or unwilling to refrain from new walking exercise activity during the trial.
• Already exercising at a level consistent with exercise intervention.
• End-stage kidney disease (ESKD) associated with the need for dialysis.
• Planned major surgery, coronary or leg revascularization during the next six months
• Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
• 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.
• Allergy to beetroot juice

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (3)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Peripheral Vascular Diseases; Mobility Limitation

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Mary McDermott, MD

CONTACT

312-503-6438; mdm608@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For the beetroot juice vs. placebo comparison, this will be a double blinded study where both the participant and the people collecting data will be blinded. For the supervised exercise vs. home-based exercise comparison, the participant and investigator will not be blinded, but the outcomes assessor will be blinded.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jeremiah Stamler Professor of Medicine

Model Details: 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 Record Dates

• First Submitted: May 22, 2023
• First Posted: September 11, 2023
• Study Start: September 8, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (3)