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

Trial Summary

What is the purpose of this trial?

Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. We hypothesize that home-based exercise combined with lower extremity revascularization will significantly improve walking performance compared to revascularization alone in patients with PAD undergoing revascularization for disabling PAD. We further hypothesize that inorganic nitrate, a major source of nitric oxide (NO) abundant in beetroot juice, will improve walking performance after lower extremity revascularization, compared to placebo. In preclinical models, NO inhibits inflammation, neointimal hyperplasia, thrombosis, and vascular smooth muscle cell migration at sites of revascularization. NO increases angiogenesis and perfusion, repairs skeletal muscle damaged by ischemia, and stimulates mitochondrial activity. In a randomized clinical trial with a 2 x 2 factorial design, we will test the following two primary hypotheses in 386 patients randomized within three months of a successful lower extremity revascularization for disabling PAD: First, that home-based exercise combined with lower extremity revascularization will improve six-minute walk distance more than revascularization alone at 6-month follow-up (Primary Aim #1). Second, that nitrate-rich beetroot juice combined with lower extremity revascularization will improve six-minute walk, compared to placebo combined with revascularization at 6-month follow-up (Primary Aim #2).

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.

What data supports the effectiveness of this treatment for peripheral arterial disease?

Research shows that beetroot juice, which is rich in dietary nitrate, can improve blood flow and walking distance in people with peripheral arterial disease. It helps by increasing nitric oxide levels, which improves blood vessel function and exercise performance. ^{1 2 3 4 5}

Is it safe to use beetroot juice and exercise for peripheral arterial disease?

Research shows that beetroot juice, which is high in dietary nitrate, is generally safe for humans and can help lower blood pressure and improve exercise performance in conditions like peripheral arterial disease and COPD (a lung condition). No significant safety concerns were reported in the studies reviewed. ^{1 2 4 6 7}

How does the treatment of exercise and beetroot juice differ from other treatments for peripheral arterial disease?

This treatment is unique because it combines exercise with beetroot juice, which is rich in dietary nitrate. The nitrate in beetroot juice can improve blood flow and oxygen delivery to muscles, enhancing exercise performance and walking ability in patients with peripheral arterial disease, unlike traditional treatments that may not focus on dietary components. ^{1 3 4 6 7}

Eligibility Criteria

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.

My vision problems make it hard for me to walk.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Moderate dose of dietary nitrate improves skeletal muscle microvascular function in patients with peripheral artery disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Body mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Acute Effects of Dietary Nitrate on Exercise Tolerance, Muscle Oxygenation, and Cardiovascular Function in Patients With Peripheral Arterial Disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Eight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. [2018]

7. Canada pubmed.ncbi.nlm.nih.gov

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men. [2018]