Response to Exercise and Nitric Oxide in PAD

NCT06657976 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU00220419
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Peripheral Artery Disease; Exercise; Intermittent Claudication; Nitric Oxide

Keywords

Peripheral artery disease; Claudication; Walking difficulty

Outcome Measures

Primary Outcomes (2)

• Delta nitrite

  Change in plasma nitrite from the beginning to the end of a maximal exercise stress test

  Baseline to 12-week follow-up

• Six-minute walk

  Change in six-minute walk distance

  From 12-weeks to 24-week follow-up

Secondary Outcomes (5)

• Calf muscle perfusion

  Baseline to 12-week follow-up

• Calf muscle perfusion

  From 12-weeks to 24-week follow-up

• Brachial artery flow-mediated dilation (FMD)

  Baseline to 12-week follow-up

• Brachial artery flow-mediated dilation (FMD)

  From 12 weeks to 24-week follow-up

• Delta nitrite

  From 12 weeks to 24-week follow-up

Other Outcomes (15)

• Dihydrobiopterin (BH2)

  From baseline to 12-week follow-up

• Dihydrobiopterin (BH2)

  From 12 week to 24-week follow-up

• Tetrahydrobiopterin (BH4)

  From baseline to 12-week follow-up

Study Arms (4)

Supervised Treadmill Exercise

EXPERIMENTAL

This group will be participating in supervised treadmill exercise for 12 weeks. Participants will walk for exercise on a treadmill 3 times per week at a center while supervised by healthcare personnel.

Behavioral: Supervised Treadmill Exercise

Attention Control Group

SHAM COMPARATOR

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.

Behavioral: Attention Control

Exercise Supplementation with Nitrate-Rich Beetroot Juice

EXPERIMENTAL

This group for "non-responders" will receive supervised exercise supplementation with nitrate-rich beetroot juice for an additional 12 weeks.

Combination Product: Nitrate-Rich Beetroot Juice + supervised exercise therapy

Exercise Supplementation with Placebo Beetroot Juice

PLACEBO COMPARATOR

This group for "non-responders" will received supervised exercise supplementation with placebo beetroot juice for the additional 12 weeks.

Combination Product: Placebo + supervised exercise therapy

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.

Also known as: Supervised Exercise Therapy

Supervised Treadmill Exercise

Attention Control BEHAVIORAL

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.

Also known as: Control

Attention Control Group

Nitrate-Rich Beetroot Juice + supervised exercise therapy COMBINATION_PRODUCT

Participants randomized to this group will drink nitrate-rich beetroot juice while engaged in supervised exercise.

Exercise Supplementation with Nitrate-Rich Beetroot Juice

Placebo + supervised exercise therapy COMBINATION_PRODUCT

Participants randomized to this group will drink placebo while engaged in supervised exercise.

Exercise Supplementation with Placebo Beetroot Juice

Eligibility Criteria

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

You may qualify if:

• An ABI less than or equal to 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 more than 0.90 and less than 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 less than 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
• Failure to complete study-run
• Unwilling to accept randomization into either group (supervised exercise or attention control)
• 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, using investigator discretion.
• End-stage kidney disease (ESKD) that is treated with hemodialysis.
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
• Allergy to beetroot juice
• Currently consuming beetroot juice, oral nitrate or nitrite, or a beetroot supplement and/or unwilling to avoid beetroot juice during the study. Participants will be asked to discontinue these items for 30 days before baseline testing and throughout the clinical trial. If the potential participant is unwilling to refrain from taking these items, they will not be eligible for the clinical trial.

Sponsors & Collaborators

• Northwestern University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Motor Activity; Intermittent Claudication; Mobility Limitation

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Mary M McDermott, MD

CONTACT

312-503-6419; mdm608@northwestern.edu

Kathryn Domanchuk, BS

CONTACT

312-503-6438; k-domanchuk@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 26, 2024
• Study Start: January 23, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (2)