NCT06032065

SMART Exercise for PAD

Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for Peripheral Artery Disease: The SMART PAD Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 210 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

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

Interventions

Type	Name	Description
BEHAVIORAL	Supervised Treadmill Exercise	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.
BEHAVIORAL	Home-Based Exercise	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.
DIETARY_SUPPLEMENT	Nitrate-rich beetroot Juice	Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.

Timeline

• Start date: 2023-09-08
• Primary completion: 2028-11-01
• Completion: 2029-03-31
• First posted: 2023-09-11
• Last updated: 2026-04-15

Locations

3 sites across 1 country: United States