NCT06657976

Response to Exercise and Nitric Oxide in PAD

Response to Exercise and Nitric Oxide in Peripheral Artery Disease: The RESIST PAD Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

RESIST PAD is a randomized trial of 200 PAD patients to establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.

Detailed description

Walking exercise is the only highly effective medical therapy for improving walking impairment in people disabled by lower extremity peripheral artery disease (PAD). However, approximately 45% of people with PAD do not meaningfully improve after an exercise intervention. Biologic pathways that mediate exercise response and biologic pathways that explain exercise non-response in PAD are unknown. Based on preliminary evidence, it is hypothesized that in PAD, exercise-induced arterial shear stress stimulates nitric oxide synthase (NOS) activity to increase nitric oxide bioavailability and improve leg perfusion, skeletal muscle mitochondrial activity, and walking ability. It is further hypothesized that exercise increases plasma nitric oxide during exercise in "responders" but does not meaningfully increase nitric oxide during exercise in "non-responders". RESIST PAD is a randomized trial of 200 PAD patients that will establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.

Conditions

• Peripheral Artery Disease
• Exercise
• Intermittent Claudication
• Nitric Oxide

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	Attention Control	This group will attend weekly one-hour educational sessions either on Zoom or in-person for 12 weeks. These sessions are on topics of interest to the typical PAD patient and may be led by study staff, physicians, or other health care workers.
COMBINATION_PRODUCT	Nitrate-Rich Beetroot Juice + supervised exercise therapy	Participants randomized to this group will drink nitrate-rich beetroot juice while engaged in supervised exercise.
COMBINATION_PRODUCT	Placebo + supervised exercise therapy	Participants randomized to this group will drink placebo while engaged in supervised exercise.

Timeline

• Start date: 2025-01-23
• Primary completion: 2029-07-01
• Completion: 2029-10-01
• First posted: 2024-10-26
• Last updated: 2025-07-11

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study