Exercise and Beetroot Juice for Peripheral Artery Disease

(RESIST Trial)

Recruiting at 1 trial location

Overseen By Kathryn Domanchuk, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Oral nitrates, Beetroot supplements

Disqualifiers: Amputation, Ischemia, Ulcer, ESKD, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how exercise and beetroot juice might aid individuals with peripheral artery disease (PAD) in improving circulation and walking ability. Researchers aim to determine if a 12-week treadmill exercise program can increase nitrite levels in the blood, which is crucial for healthy blood flow. For participants who do not experience improvements with exercise alone, the study will also assess whether adding nitrate-rich beetroot juice, a dietary supplement, can make a difference. Ideal participants are those diagnosed with PAD who have experienced challenges walking due to poor circulation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop consuming beetroot juice, oral nitrate or nitrite, and beetroot supplements for 30 days before the trial and throughout the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inorganic nitrate supplements, such as beetroot juice, are safe and well-tolerated for people with peripheral artery disease (PAD). Studies have found that these supplements can improve blood flow and exercise performance, which benefits those with PAD. No serious side effects have been reported from using beetroot juice.

Supervised treadmill exercise is often the first recommended treatment for PAD, commonly suggested to help manage the condition. Known for its benefits, it carries a low risk of harm. While exercising, new symptoms like chest pain might occur, but healthcare providers closely monitor this.

Overall, both beetroot juice and supervised exercise are considered safe and may offer health benefits for people with PAD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Peripheral Artery Disease (PAD) because they introduce innovative approaches beyond traditional methods like medication and surgical interventions. The use of nitrate-rich beetroot juice is particularly interesting because it can enhance blood flow by increasing nitric oxide levels in the body, which may improve exercise performance and overall circulation. Additionally, combining this with supervised treadmill exercise provides a structured, non-invasive way to potentially increase mobility and quality of life for PAD patients. This approach not only targets physical activity but also leverages nutritional supplementation to address the condition, offering a holistic alternative to the standard care options.

What evidence suggests that exercise and beetroot juice might be effective treatments for peripheral artery disease?

Research has shown that supervised treadmill exercise, one of the treatments in this trial, can significantly help people with peripheral artery disease (PAD) walk longer distances. In one study, participants who exercised on a treadmill increased their walking distance by an average of 32.9 meters compared to those who did not exercise.

Regarding beetroot juice, another treatment option in this trial, studies indicate that it raises nitric oxide levels, improving blood flow and exercise performance in people with PAD. Early research suggests that beetroot juice can help people with PAD exercise with less pain and more stamina. This trial will test the combination of treadmill exercise and beetroot juice to determine if they together may help manage PAD symptoms. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with Peripheral Arterial Disease (PAD), specifically those who experience intermittent claudication, which is muscle pain during exercise due to poor blood flow. Participants should be able to perform treadmill exercises and have not been involved in regular exercise programs recently.

Inclusion Criteria

My ABI score drops significantly after a physical leg test.

An ABI less than or equal to 0.90 at baseline

I have been diagnosed with PAD based on vascular tests or angiography.

Exclusion Criteria

Abnormal baseline stress test without subsequent clearance for exercise by physician

I am not planning any major surgery or heart/leg artery procedures in the next 6 months.

I have a current foot ulcer on the bottom of my foot.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 12-week supervised treadmill exercise program or attend educational sessions

12 weeks

3 visits per week (in-person) for exercise group; 1 visit per week (in-person or virtual) for control group

Supplementation

Non-responders receive an additional 12 weeks of exercise with either nitrate-rich or placebo beetroot juice

12 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for changes in six-minute walk distance and other biomarkers

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nitrate-Rich Beetroot Juice + supervised exercise therapy
• Placebo + supervised exercise therapy
• Supervised Treadmill Exercise

Trial Overview The RESIST PAD study tests if a 12-week supervised treadmill exercise program can increase nitric oxide levels compared to a control group. It also examines if adding nitrate-rich beetroot juice enhances benefits for those who don't initially respond well to the exercise alone.

How Is the Trial Designed?

Group I: Supervised Treadmill Exercise Experimental Treatment 1 Intervention

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.

Group II: Exercise Supplementation with Nitrate-Rich Beetroot Juice Experimental Treatment 1 Intervention

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

Group III: Exercise Supplementation with Placebo Beetroot Juice Placebo Group 1 Intervention

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

Group IV: Attention Control Group Placebo Group 1 Intervention

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.

Supervised Treadmill Exercise is already approved in United States, European Union for the following indications:

Approved in United States as Supervised Exercise Therapy (SET) for:

• Lower Extremity Peripheral Artery Disease (PAD)

Approved in European Union as Supervised Exercise Therapy (SET) for:

• Lower Extremity Peripheral Artery Disease (PAD)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 210 participants with peripheral artery disease (PAD), a 6-month supervised exercise therapy (SET) program significantly reduced systolic blood pressure by 12 mm Hg, pulse pressure by 9 mm Hg, and heart rate by 7 beats per minute during exercise compared to a control group.

The improvements in cardiovascular health metrics (blood pressure and heart rate) were associated with better walking performance, indicating that SET not only enhances walking ability but also positively impacts cardiovascular health in individuals with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supervised exercise therapy on blood pressure and heart rate during exercise, and associations with improved walking performance in peripheral artery disease: Results of a randomized clinical trial. Slysz, JT., Tian, L., Zhao, L., et al.[2021]

The Group Oriented Arterial Leg Study (GOALS) is a randomized controlled trial aimed at improving walking performance in individuals with lower extremity peripheral artery disease (PAD) through a Group-Mediated Cognitive Behavioral (GMCB) intervention, which encourages home-based walking exercises.

The primary outcome of the study is the change in six-minute walk performance after 6 months, with potential significant public health implications if the intervention proves effective in enhancing functional performance in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Group Oriented Arterial Leg Study (GOALS) to improve walking performance in patients with peripheral arterial disease. McDermott, MM., Domanchuk, K., Liu, K., et al.[2021]

A 12-week supervised treadmill-walking program significantly improved calf-muscle strength and endurance in 22 individuals with peripheral arterial disease (PAD), indicating its effectiveness as a treatment.

The study also found that improvements in calf-muscle endurance were correlated with enhanced walking capacity, suggesting that strengthening these muscles can help individuals with PAD walk better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supervised treadmill-walking training on strength and endurance of the calf muscles of individuals with peripheral arterial disease. Wang, J., Zhou, S., Bronks, R., et al.[2006]

In a study of 63 patients with peripheral artery disease (PAD) undergoing a 6-month supervised exercise therapy (SET) program, an increase in walking speed of 0.03 m/s or greater was identified as the minimal clinically important difference (MCID), indicating meaningful improvement in walking ability.

The study established specific thresholds for small and substantial improvements in walking speed, which can help clinicians set realistic goals and assess progress in claudicating patients with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudicating patients with peripheral artery disease have meaningful improvement in walking speed after supervised exercise therapy. Rahman, H., Pipinos, II., Johanning, JM., et al.[2022]

A survey of 91 Dutch vascular surgeons revealed that 75.4% would refer newly diagnosed patients with intermittent claudication for supervised exercise therapy (SET), indicating a strong belief in its importance as a treatment for peripheral arterial occlusive disease (PAOD).

Surgeons expressed that SET should be combined with lifestyle management and emphasized that despite its recognized benefits, SET is underutilized in clinical practice, particularly for patients with co-morbidities or significant artery stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When is supervised exercise therapy considered useful in peripheral arterial occlusive disease? A nationwide survey among vascular surgeons. Lauret, GJ., van Dalen, HC., Hendriks, HJ., et al.[2018]

Supervised exercise therapy (SET) significantly increases daily physical activity in patients with intermittent claudication (IC), with an average increase of about 803 steps per day compared to usual care.

Home-based exercise therapy (HBET) also shows a positive effect on physical activity, with an increase of approximately 980 steps per day, while endovascular revascularization (ER) did not demonstrate a statistically significant improvement over control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Supervised Exercise, Home Based Exercise and Endovascular Revascularisation on Physical Activity in Patients With Intermittent Claudication: A Network Meta-analysis. van den Houten, MML., Hageman, D., Gommans, LNM., et al.[2020]

PoleStriding exercise significantly improved exercise tolerance and reduced claudication pain in patients with peripheral arterial disease (PAD), as shown by a randomized trial with 52 participants.

Vitamin E supplementation did not provide any additional benefits in terms of pain relief or exercise capacity compared to the PoleStriding exercise alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PoleStriding exercise and vitamin E for management of peripheral vascular disease. Collins, EG., Edwin Langbein, W., Orebaugh, C., et al.[2022]

Supervised exercise therapy (SET) has been effectively integrated into cardiopulmonary rehabilitation programs over a 3-year period, demonstrating its potential to improve walking distance for patients with symptomatic peripheral artery disease (PAD).

The recent decision by the Centers for Medicare and Medicaid to cover SET could significantly enhance its adoption in clinical practice, providing a structured approach for rehabilitation therapists to implement SET in their programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience Implementing Supervised Exercise Therapy for Peripheral Artery Disease. Salisbury, DL., Whipple, MO., Burt, M., et al.[2022]

A supervised exercise therapy (SET) program for patients with intermittent claudication showed a 20% improvement in walking distance, increasing from an average of 298.5 meters to 360 meters, based on a study involving 155 patients over nearly two years.

The program is cost-effective compared to traditional physiotherapy and is designed to be accessible, with efforts made to increase participation through additional classes and venues, demonstrating the potential for successful implementation of community-based health interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of a supervised exercise therapy programme. Murgitroyd, E., Fraser, S., Hebson, A., et al.[2020]

Supervised exercise therapy (SET) for patients with intermittent claudication (IC) is very safe, with only eight adverse events reported over 82,725 hours of training, resulting in a complication rate of just one event per 10,340 patient-hours.

The study suggests that routine cardiac screening before starting SET is unnecessary, which may encourage more healthcare providers to recommend this effective treatment for IC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of supervised exercise therapy in patients with intermittent claudication. Gommans, LN., Fokkenrood, HJ., van Dalen, HC., et al.[2022]

Only 30.4% of vascular surgeons reported access to supervised exercise programs (SEPs) for managing peripheral arterial disease (PAD), highlighting a significant accessibility issue.

Structured home-based exercise programs (HEPs) were found to be effective alternatives, significantly improving functional capacity and quality of life compared to standard advice, although SEPs were superior in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Availability of supervised exercise programs and the role of structured home-based exercise in peripheral arterial disease. Makris, GC., Lattimer, CR., Lavida, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6202165/

Beet the Best? Dietary Inorganic Nitrate to Augment ... Our data suggests that increasing plasma nitrite prior to exercise may allow PAD subjects to train with less pain, at higher workloads for longer durations.

2. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1398108/full

Effects of short-term dietary nitrate supplementation on ... Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1089860325000266

Exploring the therapeutic potential of beetroot juice in ... Beetroot juice boosts nitric oxide, improving blood flow and PAD management. Beetroot juice enhances exercise performance and microvascular function in PAD.

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCRESAHA.118.313131?next=/answers/beetroot-exercise-endurance/beetroot/

Beet the Best? | Circulation Research Specifically, our data suggest that increasing plasma nitrite before exercise may allow PAD subjects to train with less pain, at higher workloads for longer ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05624125

BEETroot Juice to Reverse Functional Impairment in PAD Preliminary evidence suggests that beetroot juice has both acute and chronic effects on walking performance in PAD. The primary outcome will measure the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11257697/

Effects of short-term dietary nitrate supplementation on ... Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02553733

Effect of Beetroot Juice on Coronary Blood Flow and ... One open-label study showed that acute consumption of beetroot juice improved 6 min walk performance, reduced blood pressure, and enhanced leg muscle ...

8. cureus.com cureus.com/articles/382381-efficacy-of-beetroot-juice-in-patients-with-peripheral-artery-disease-a-systematic-review

Efficacy of Beetroot Juice in Patients With Peripheral Artery ... Overall, findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary ...

9. pubs.rsc.org pubs.rsc.org/en/content/articlehtml/2024/fo/d3fo03749e

Increased nitrate intake from beetroot juice over 4 weeks ... From a practical viewpoint, the results of our study suggest no long-term effects on vascular function or blood pressure from the daily ...