Exercise Program for Peripheral Arterial Disease

(NICE Trial)

Overseen By Andrew W. Gardner, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Must not be taking: Cilostazol, Pentoxifylline

Disqualifiers: Active cancer, Kidney failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a 3-month, prospective, randomized controlled clinical trial designed to address the efficacy of the Non-Ischemic Exercise (NICE) program to improve exercise and vascular outcome measures in patients with peripheral artery disease (PAD).

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 started taking cilostazol or pentoxifylline (medications for leg pain) within the last three months.

What data supports the effectiveness of the treatment NICE program, Non-Ischemic Exercise program, for Peripheral Arterial Disease?

Research shows that exercise programs can improve walking ability and blood flow in people with Peripheral Arterial Disease (PAD). Studies have found that both high-intensity and structured home-based exercise programs can lead to better walking distances and improved blood circulation, making exercise a beneficial treatment for PAD. ^{1 2 3 4 5}

Is the exercise program for peripheral arterial disease safe for humans?

Home-based exercise programs for people with peripheral arterial disease, like the NICE program, have been shown to be generally safe, with a very low rate of adverse events. In a review of 27 studies involving 1642 participants, only four related adverse events were reported over 147,810 patient-hours, indicating a low risk of complications. ^{2 6 7 8 9}

How is the NICE program treatment for Peripheral Arterial Disease different from other treatments?

The NICE program is unique because it focuses on a non-ischemic exercise approach, which means it emphasizes exercise that does not cause pain, unlike other treatments that may involve high-intensity exercise near maximal pain. This makes it a more sustainable and cost-effective option for improving mobility and quality of life in patients with Peripheral Arterial Disease. ^{1 2 7 10 11}

Research Team

Andrew W. Gardner, Ph.D

Principal Investigator

Professor, Department of Medicine, Cardiology

Eligibility Criteria

This trial is for individuals aged 60 or older with Peripheral Artery Disease (PAD) who experience leg pain during walking, confirmed by a treadmill test and an Ankle-Brachial Index (ABI) of <=0.90. Candidates should not have started certain PAD medications recently, had recent revascularization, or have conditions that could affect exercise tolerance other than PAD.

Inclusion Criteria

I have leg pain when walking, confirmed by a treadmill test.

My ankle blood pressure drops significantly after exercise.

I have leg pain when walking.

Exclusion Criteria

My blood flow in legs is normal, both at rest and after exercise.

I have had or will have surgery to improve blood flow to my limbs.

I started taking medication for leg pain when walking in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either the NICE or Standard exercise program and perform supervised treadmill walking for 3 months

12 weeks

Regular supervised sessions

Follow-up

Participants are monitored for changes in exercise and vascular outcomes after the treatment phase

4 weeks

Treatment Details

Interventions

• NICE program

Trial Overview The study tests the Non-Ischemic Exercise (NICE) program's effectiveness over three months in improving exercise capacity and vascular health in patients with PAD. Participants are randomly assigned to either the NICE program or a control group to compare outcomes.

Participant Groups

Group I: Non-Ischemic Exercise (NICE) exercise program Experimental Treatment 1 Intervention

Patients will perform supervised treadmill walking for 3 months. Patients randomized to the NICE program will walk intermittently at a slow speed of approximately 1.4 mph for only 2-3 minute bouts that do not elicit claudication pain.

Group II: Standard exercise program Active Control 1 Intervention

Patients will perform supervised treadmill walking for 3 months. Patients randomized to the Standard program will walk intermittently at a speed of approximately two mph to near maximal claudication pain.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Exercise is an effective nonsurgical therapy for peripheral arterial disease, leading to improved walking tolerances in patients.

Regular exercise can enhance skeletal muscle metabolism and improve blood distribution, contributing to better overall vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and peripheral vascular disease. Sidoti, SP.[2004]

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]

Both low-intensity and high-intensity exercise rehabilitation programs significantly improved physical function and health-related quality of life in patients with peripheral arterial disease (PAD), with similar outcomes after 6 months of training.

Patients in both groups experienced a remarkable increase in claudication distance (over 100% improvement), indicating that low-intensity exercise can be as effective as high-intensity exercise for enhancing functional independence in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. Gardner, AW., Montgomery, PS., Flinn, WR., et al.[2022]

In a study of 47 patients with peripheral arterial disease, a high-intensity interval exercise program led to significant improvements in walking ability, as measured by a rehabilitation score.

The program was safe, with no adverse events reported, indicating that patients with peripheral arterial disease can tolerate high-intensity exercise without risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training for intermittent claudication in a vascular rehabilitation program. Adams, J., Ogola, G., Stafford, P., et al.[2019]

A 6-month structured pain-free exercise program significantly improved ankle-brachial index (ABI) values and walking distances in 239 patients with peripheral artery disease (PAD), demonstrating its efficacy in enhancing vascular health.

The exercise regimen was safe and well-tolerated, with 88% of participants successfully completing the prescribed training, leading to improvements in both functional capacity and cardiovascular health indicators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structured pain-free exercise progressively improves ankle-brachial index and walking ability in patients with claudication and compressible arteries: an observational study. Manfredini, F., Traina, L., Gasbarro, V., et al.[2022]

Supervised exercise therapy (SET) is an effective first-line treatment for patients with chronic lower extremity peripheral artery disease (PAD), improving walking performance and quality of life, yet it is underutilized across Europe.

A survey of 131 responders from 17 countries revealed that only 59% of European countries have SET programs for PAD, with significant variability in program availability, reimbursement, and structure, highlighting the need for better guidance on exercise therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised exercise training in patients with lower extremity peripheral artery disease. Lanzi, S., Belch, J., Brodmann, M., et al.[2022]

A randomized trial involving 60 patients with peripheral artery disease (PAD) will compare a structured home-based exercise program to a control group, focusing on improving pain-free walking distance and overall quality of life over 6 months.

The home-based exercise program is designed to be pain-free and may offer a sustainable and cost-effective alternative for improving mobility in PAD patients, potentially benefiting both patients and healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Home-Based Pain-Free Exercise versus Walking Advice in Patients with Peripheral Artery Disease: A Randomized Controlled Trial. Manfredini, F., Lamberti, N., Traina, L., et al.[2021]

Home-based exercise programs (HBEPs) for individuals with intermittent claudication (IC) are safe, with only four adverse events reported over 147,810 patient-hours, resulting in a complication rate of one event per 36,953 patient-hours.

Most adverse events were cardiac-related and occurred during high levels of claudication pain, suggesting that while HBEPs are generally safe, monitoring and possibly cardiac screening may be beneficial for those engaging in more intense exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of home-based exercise for people with intermittent claudication: A systematic review. Waddell, A., Seed, S., Broom, DR., et al.[2022]

In a study of 400 patients with peripheral artery disease (PAD), those who participated in a home-based walking program had a significantly higher 7-year survival rate, especially women (90% survival) compared to men (82%) and control groups (45% for both).

The exercise group also experienced significantly lower rates of hospitalizations and amputations compared to the control group, indicating that a pain-free exercise program can lead to better long-term health outcomes for PAD patients, regardless of sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study. Lamberti, N., Traina, L., Savriè, C., et al.[2023]

A vascular rehabilitation program for 68 patients with lower extremity arterial occlusive disease led to significant improvements in exercise tolerance, with 88% of participants increasing their walking distances by over 100%.

The program was safe, with no deaths or major complications reported, and 84% of participants maintained or improved their walking distances during long-term follow-up, alongside notable reductions in cholesterol and triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular rehabilitation: benefits of a structured exercise/risk modification program. Williams, LR., Ekers, MA., Collins, PS., et al.[2017]

Active exercise therapy significantly improves outcomes for patients with early stages of peripheral arterial occlusive disease (PAOD), as demonstrated in a successful outpatient claudication group program involving 26 patients.

The use of a newly developed pedal ergometer allowed for controlled endurance training, resulting in a notable increase in pain-free walking distance for 17 out of the 26 participants, supported by improvements in arterial hemodynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Success of an outpatient claudication group training program for patients with peripheral arterial occlusive disease (PAOD): the Tübingen model. Klyscz, T., Jünger, M., Jünger, I., et al.[2006]

References

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

Exercise and peripheral vascular disease. [2004]

2. England pubmed.ncbi.nlm.nih.gov

Availability of supervised exercise programs and the role of structured home-based exercise in peripheral arterial disease. [2018]

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

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. [2022]

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

High-intensity interval training for intermittent claudication in a vascular rehabilitation program. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Structured pain-free exercise progressively improves ankle-brachial index and walking ability in patients with claudication and compressible arteries: an observational study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Supervised exercise training in patients with lower extremity peripheral artery disease. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Home-Based Pain-Free Exercise versus Walking Advice in Patients with Peripheral Artery Disease: A Randomized Controlled Trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety of home-based exercise for people with intermittent claudication: A systematic review. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study. [2023]

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

Vascular rehabilitation: benefits of a structured exercise/risk modification program. [2017]

11. Czech Republic pubmed.ncbi.nlm.nih.gov

Success of an outpatient claudication group training program for patients with peripheral arterial occlusive disease (PAOD): the Tübingen model. [2006]