Exercise and Beetroot Juice for Peripheral Arterial Disease

(IMPACT PAD Trial)

Recruiting at 7 trial locations

Overseen By Mary M McDermott, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Northwestern University

Must not be taking: Sildenafil, Tadalafil, Beetroot

Disqualifiers: Amputation, Gangrene, Dementia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 18

Duration: 6 months

386 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether home-based exercise and nitrate-rich beetroot juice can help individuals with Peripheral Arterial Disease (PAD) improve their walking ability. Researchers aim to determine if these treatments are more effective than surgery alone in enhancing blood flow in the legs. Individuals who have undergone a successful procedure to improve leg blood flow and experience walking difficulties due to PAD may be suitable candidates. Participants should not frequently consume beetroot or be on certain medications and must be willing to try exercise and beetroot juice as part of the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 cannot participate if you are currently taking sildenafil, tadalafil, or related drugs. Additionally, you must stop consuming beetroot juice, oral nitrate or nitrite, or 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 exercising at home is generally safe for people with Peripheral Arterial Disease (PAD). Studies have found that it can significantly improve walking distance and speed. Many people find this type of exercise manageable and notice they can walk longer distances.

Regarding nitrate-rich beetroot juice, research suggests it is also safe and well-tolerated for those with PAD. It may help improve blood flow and overall exercise capacity. These findings are encouraging, indicating that both treatments have been tested for safety and have shown positive results in past studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Peripheral Arterial Disease (PAD) because they offer a natural approach that could complement or enhance existing therapies like medications and supervised exercise programs. The use of nitrate-rich beetroot juice is particularly intriguing because it may improve blood flow by increasing nitric oxide levels, which can enhance vascular function and reduce symptoms of PAD. Additionally, combining home-based exercise with beetroot juice provides a potentially accessible and convenient treatment option for patients who may have difficulty accessing traditional in-clinic exercise programs. By exploring these innovative strategies, researchers hope to discover more effective and easily implementable ways to manage PAD symptoms.

What evidence suggests that this trial's treatments could be effective for improving walking performance in PAD patients?

Research has shown that drinking beetroot juice, which is high in nitrates, might help people with Peripheral Arterial Disease (PAD) walk better. Studies have found that it increases nitric oxide, improving blood flow and making exercise easier. This improvement may allow for longer walks with less pain. Beetroot juice has also been shown to lower blood pressure, which aids in managing PAD. In this trial, one group will engage in home-based exercise while drinking nitrate-rich beetroot juice, potentially enhancing these benefits and enabling more effective training with less discomfort. Another group will receive attention control with nitrate-rich beetroot juice. Additionally, some participants will receive placebo beetroot juice without nitrate, either with home-based exercise or attention control. Overall, promising evidence suggests that beetroot juice and exercise together can improve walking in people with PAD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for patients with Peripheral Artery Disease (PAD) who have undergone revascularization but still experience walking difficulties. Participants should be within three months post-successful revascularization and willing to follow a home-based exercise program or consume beetroot juice.

Inclusion Criteria

My surgery to improve blood flow was successful.

I had surgery to improve blood flow in my legs between 1 and 3 months ago.

Willingness to adhere to the interventions and complete follow-up testing

Exclusion Criteria

Dementia and psychiatric illness with sufficient impairment to prevent full engagement in all aspects of the trial per investigator's discretion

I am not willing to be randomly assigned to a study group.

Allergy to beetroot juice

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in home-based exercise and consume nitrate-rich beetroot juice or placebo for six months

6 months

Regular home-based activities

Follow-up

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

6 months

Follow-up assessments at 6 months

Extended Follow-up

Participants are monitored for long-term outcomes such as prevention of hemodynamic failure and mobility improvements

12 months

Assessments at 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Home Based Exercise
• Nitrate Rich Beetroot Juice
• Placebo Beetroot Juice Without Nitrate

Trial Overview

The study tests if home-based exercises or nitrate-rich beetroot juice can improve walking performance after leg artery surgery, compared to usual care alone. It's a randomized trial where participants are assigned by chance to one of four groups: exercise, placebo juice, nitrate juice, or attention control.

How Is the Trial Designed?

Group I: Home based exercise + nitrate rich beetroot juice Experimental Treatment 2 Interventions

This group will be participating in home based exercise and drinking nitrate rich beetroot juice for six months.

Group II: Attention control + nitrate-rich beetroot juice Experimental Treatment 2 Interventions

This group will be participating in attention control and drinking nitrate rich beetroot juice for six months.

Group III: Home-based exercise + placebo Placebo Group 2 Interventions

This group will be participating in home based exercise and drinking placebo beetroot juice with nitrate removed for six months.

Group IV: Attention control + placebo Placebo Group 2 Interventions

This group will be participating in attention control and drinking placebo beetroot juice with nitrate removed for six months.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Rancho Research Institute

Collaborator

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Wake Forest University

Collaborator

Trials

193

Recruited

151,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

Dartmouth-Hitchcock Medical Center

Collaborator

Trials

548

Recruited

2,545,000+

Published Research Related to This Trial

A moderate dose of dietary nitrate from beetroot juice significantly improved skeletal muscle microvascular function and increased the 6-minute walking distance in patients with peripheral artery disease (PAD), based on a study involving 10 participants.

The improvements in microvascular function were positively correlated with better walking distances, suggesting that dietary nitrate may enhance blood flow and exercise recovery in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate dose of dietary nitrate improves skeletal muscle microvascular function in patients with peripheral artery disease. Pekas, EJ., Anderson, CP., Park, SY.[2023]

In a study involving 18 patients with peripheral arterial disease, both nitrate-rich vegetables and beetroot juice significantly increased plasma nitrate and nitrite levels, with beetroot juice showing the highest increase.

Despite the increase in plasma nitrate and nitrite, there were no improvements in exercise tolerance, muscle oxygenation, or cardiovascular function, indicating that higher nitrate levels do not necessarily enhance physical performance in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Effects of Dietary Nitrate on Exercise Tolerance, Muscle Oxygenation, and Cardiovascular Function in Patients With Peripheral Arterial Disease. van der Avoort, CMT., van Loon, LJC., Verdijk, LB., et al.[2022]

Dietary supplementation with beetroot juice significantly increased plasma nitrite levels, which are linked to improved nitric oxide production, and led to longer walking times before experiencing claudication pain in patients with peripheral arterial disease (PAD).

The study, involving 8 subjects in a randomized crossover design, demonstrated that beetroot juice not only enhanced exercise tolerance but also reduced oxygen extraction in the gastrocnemius muscle during exercise, indicating better oxygen delivery to tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. Kenjale, AA., Ham, KL., Stabler, T., et al.[2021]

In a study involving 15 COPD patients, acute ingestion of beetroot juice significantly improved exercise capacity, allowing patients to exercise longer at a submaximal workload compared to a placebo.

Beetroot juice also led to notable reductions in both resting and exercise-induced blood pressure, indicating potential cardiovascular benefits alongside improved exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. Berry, MJ., Justus, NW., Hauser, JI., et al.[2018]

Acute dietary nitrate supplementation from beetroot juice significantly increased plasma nitrate and nitrite levels and reduced resting arterial pulse wave velocity, indicating a biological effect on vascular function.

However, despite these systemic changes, the supplementation did not enhance blood flow or brachial artery dilation during graded handgrip exercise in healthy young men, suggesting that its benefits may not extend to improving exercise-induced blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men. Kim, JK., Moore, DJ., Maurer, DG., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Effects of short-term dietary nitrate supplementation on ...

These results add to the literature regarding the blood pressure lowering potential of nitrate-rich beetroot juice in older adults with PAD.

2.

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 ...

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.

pmc.ncbi.nlm.nih.gov

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

Beet the Best? Dietary Inorganic Nitrate to Augment ...

Specifically, our data suggests that increasing plasma nitrite prior to exercise may allow PAD subjects to train with less pain, at higher workloads for longer ...

5.

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 ...

In conclusion, while beetroot juice intake may offer potential benefits such as enhanced exercise capacity and reduced blood pressure in PAD ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39423932/

Safety and efficacy of home-based walking exercise for ...

Conclusions: Among people with PAD, home-based exercise improved 6MW by at least 20 meters in 54.9% of people. Older age, female sex, Black race ...

7.

jvascsurg.org

jvascsurg.org/article/S0741-5214(24)01967-0/abstract

Safety and efficacy of home-based walking exercise for ...

Among people with PAD, home-based exercise improved 6MW by at least 20 meters in 54.9% of people. Older age, female sex, Black race, and specific comorbidities ...

8.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/1707722

Home-Based Walking Exercise Intervention in Peripheral ...

A home-based walking exercise program significantly improved walking endurance, physical activity, and patient-perceived walking endurance and speed in PAD ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02462824?term=AREA%5BBasicSearch%5D(HONOR%20and%20PAD)&rank=1

Study Details | Patient Centered Home Exercise Program ...

The purpose of this study is to determine the effects of a home-based exercise intervention on walking ability in people with peripheral artery disease . In 200 ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8419477/

Effect of Home-based Exercise Therapy for Peripheral ...

McDermott et al reported a 34% increase in WIQ distance score and a 32% increase in WIQ speed score from baseline after 6 months of home exercise. The present ...