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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new exercise program called the Non-Ischemic Exercise (NICE) program, designed to help individuals with peripheral artery disease (PAD) improve exercise capacity and blood flow. The trial compares two exercise methods: one involves walking slowly without pain, and the other involves walking faster until pain occurs. Suitable candidates for this trial experience leg pain when walking due to PAD and have had this condition for some time. As an unphased trial, this study provides a unique opportunity to explore innovative exercise methods that could enhance quality of life.

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 prior data suggests that the NICE program is safe for patients with peripheral artery disease?

Research has shown that home-based exercise programs for people with peripheral arterial disease (PAD), such as the NICE program, are generally safe. These programs have a very low rate of side effects. The NICE program includes slow, short walks that avoid claudication pain, a common leg pain during exercise for people with PAD. By preventing this pain, the program improves walking ability and reduces discomfort. Overall, the NICE program is well-tolerated and does not raise significant safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the NICE exercise program for Peripheral Arterial Disease because it offers a gentler approach to exercise that doesn't push patients to the point of pain. Unlike the standard exercise programs that encourage walking to the brink of maximal claudication pain, the NICE program involves slower, shorter treadmill walking sessions without inducing pain. This could make it more accessible and sustainable for patients, potentially improving adherence and overall outcomes.

What evidence suggests that this trial's exercise programs could be effective for peripheral artery disease?

Research shows that exercise programs can help people with peripheral artery disease (PAD). Studies have found that both gentle and more intense exercise can improve walking ability and overall quality of life for these patients. In this trial, participants will join different exercise programs through random assignment. The NICE program, one study arm, focuses on slow, short walks to prevent pain and has shown potential benefits. Structured exercise has proven to enhance walking ability and overall health in people with PAD. These findings suggest that the NICE program could effectively help individuals with PAD improve their exercise habits and blood vessel health. ^{1 2 3 5 6}

Who Is on the Research Team?

Andrew W. Gardner, Ph.D

Principal Investigator

Professor, Department of Medicine, Cardiology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/11178340

Project Details - NIH RePORTER PROJECT NARRATIVE The NICE program, in which people with peripheral artery disease walk slower and for shorter periods of intermittent pain-free walking ...

2. withpower.com withpower.com/trial/phase-peripheral-arterial-disease-5-2023-c6c4f

Exercise Program for Peripheral Arterial Disease (NICE Trial) Both low-intensity and high-intensity exercise rehabilitation programs significantly improved physical function and health-related quality of life in patients ...

3. acc.org acc.org/Latest-in-Cardiology/Articles/2025/04/02/13/44/Exercise-Therapy-in-Symptomatic-Peripheral-Artery-Disease

Exercise Therapy in Symptomatic Peripheral Artery Disease Structured exercise programs have been shown to improve walking performance, functional status, and QOL in patients with symptomatic PAD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02462824

Patient Centered Home Exercise Program for Peripheral ... 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.

5. cms.gov cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=287

NCA - Supervised Exercise Therapy (SET) for Symptomatic ... Initial results of a 12-week, institution-based, supervised exercise rehabilitation program for the management of peripheral arterial disease. Vascular 2010 ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000000623

Optimal Exercise Programs for Patients With Peripheral ... 6 months of unsupervised intermittent walking exercise was demonstrated to improve time walked to onset of pain and peak walking time (PWT).