Heating Treatments for Peripheral Artery Disease

(EPR Trial)

Overseen By Kris Gray, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Disqualifiers: Pregnant, Decisional impairment, CAD, others

Compensation: Varies

Number of Visits: 1

Duration: 3-4 hours per visit

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether heat treatments can aid individuals with Peripheral Artery Disease (PAD) during exercise. PAD reduces blood flow to the limbs, often causing pain while walking. The trial includes different groups: some will use heat, such as warm baths or heating suits, while others will not. It seeks participants diagnosed with PAD who experience pain when walking but not at rest. Healthy individuals without chronic illnesses are also invited to participate. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking medical insights.

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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

Research has shown that heat therapy is generally safe for people with peripheral artery disease (PAD). Studies on the heating suit indicate it can improve heart and blood vessel function, performing as well as other treatments. No major safety issues have emerged.

For warm water immersion of the lower limbs, studies have demonstrated increased blood flow and good tolerance among participants. They experienced improved blood flow without significant side effects, suggesting relative safety.

Regarding warm baths, research indicates positive responses from participants. They reported better walking ability and improved blood vessel health without major side effects.

These treatments have shown potential in aiding PAD patients. As this study is in its early stages, the primary goal is to ensure safety, with any possible risks closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these heating treatments for Peripheral Artery Disease (PAD) because they explore alternative ways to improve blood flow and reduce symptoms without relying on medication or surgery. Unlike standard treatments that often involve drugs like antiplatelet agents and statins, these methods use external heat applications, such as warm baths, heating suits, and limb immersion, to increase blood circulation. This approach could offer a non-invasive option with fewer side effects, potentially improving patients' quality of life by enhancing exercise tolerance and reducing discomfort during activities.

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

Research has shown that heat therapy can benefit people with peripheral artery disease (PAD). In this trial, participants will be assigned to different treatment arms to evaluate the effects of various heat-based treatments. Some participants will use a heating suit, while others will soak their legs in hot water. Studies have demonstrated that these methods increase blood flow to the limbs, potentially easing symptoms like leg pain when walking. Additionally, heat therapy can help participants walk farther and lower resting blood pressure. While a warm bath, another treatment arm in this trial, can also lower blood pressure, it might not improve walking ability or overall blood vessel health. Overall, these heat-based treatments seem promising for managing PAD symptoms. ^{1 2 6 7 8}

Who Is on the Research Team?

Jian Cui

Principal Investigator

Penn State College of Medicine

Are You a Good Fit for This Trial?

This trial is for men and women aged 21-85 with Peripheral Artery Disease (PAD), specifically those who can consent, speak English, have an ankle-brachial index below 0.9 without rest pain, and are generally healthy otherwise. It excludes pregnant or nursing women, individuals under 21 or with decisional impairments, prisoners, and those with other chronic diseases or recent severe cardiac events.

Inclusion Criteria

I have been diagnosed with peripheral artery disease (PAD).

Any race or ethnicity

I do not have any current severe illnesses.

Exclusion Criteria

Pregnant or nursing women

I have difficulty making decisions due to a mental condition.

I have a chronic condition like heart, lung, muscle disease, or diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo various heating interventions followed by treadmill walking using the Gardner protocol. BP, HR, and NIRS are continuously measured.

3-4 hours per visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gardner walking protocol
• Heating Suit
• Lower limb warm water immersion
• Neutral Bath
• Warm Bath
• Without Heating

Trial Overview The study tests if heating methods like a heating suit or warm water immersion before exercise can reduce the sympathetic nervous system's response in PAD patients. The hypothesis suggests that heat may make muscle receptors less sensitive to stress from exercise.

How Is the Trial Designed?

Group I: PAD warm bath Experimental Treatment 2 Interventions

Subjects will take a warm bath. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group II: PAD lower limb warm water immersion Experimental Treatment 2 Interventions

Subjects will place their lower legs in warm water. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group III: PAD heating suit Experimental Treatment 2 Interventions

Whole body heating with the suit will be performed. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group IV: Healthy subjects warm bath Experimental Treatment 2 Interventions

Subjects will take a warm bath. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group V: Healthy subjects lower limb immersion Experimental Treatment 2 Interventions

Subjects will place their lower legs in warm water. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group VI: Healthy subjects heat suit Experimental Treatment 2 Interventions

Whole body heating with the suit will be performed. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group VII: Healthy subjects without heating Placebo Group 2 Interventions

Subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group VIII: Healthy subjects neutral bath Placebo Group 2 Interventions

Subjects will take a neutral bath. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group IX: PAD without heating Placebo Group 2 Interventions

Subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Group X: PAD neutral bath Placebo Group 2 Interventions

Subjects will take a neutral bath. Then, subjects will walk on a treadmill using the Gardner protocol until the patient says they want to stop. BP, HR and NIRS will be continuously measured during Gardner protocol. Skin blood flow, skin temperature and BP will be measured in the supine position before and after the Gardner protocol.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

Heat therapy, involving spa bathing and calisthenics, improved walking distance and resting blood pressure in patients with peripheral arterial disease (PAD) over 12 weeks, showing excellent adherence and tolerance among participants.

Both heat therapy and traditional exercise led to similar improvements in functional ability, suggesting that heat therapy could be a viable alternative for PAD patients who struggle with conventional exercise due to pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heat therapy vs. supervised exercise therapy for peripheral arterial disease: a 12-wk randomized, controlled trial. Akerman, AP., Thomas, KN., van Rij, AM., et al.[2020]

In a pilot study involving 6 patients with peripheral artery disease (PAD), acute lower leg heating significantly increased blood flow in the popliteal artery, demonstrating a duration-dependent effect after treatment.

The 6-minute walk distance improved by 10% and 12% following 15 and 45 minutes of heating, respectively, indicating that even short heating sessions can enhance exercise capacity in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Lower Leg Heating Increases Exercise Capacity in Patients With Peripheral Artery Disease. Pellinger, TK., Neighbors, CB., Simmons, GH.[2020]

Heat treatment (HT) significantly reduces the exaggerated blood pressure response during exercise in rats with peripheral artery disease (PAD), suggesting a potential therapeutic approach for managing this condition.

The beneficial effects of HT are linked to a reduction in the activity of the P2X receptor pathway, which is involved in the exaggerated exercise pressor reflex, indicating a specific mechanism through which HT operates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heat treatment improves the exaggerated exercise pressor reflex in rats with femoral artery occlusion via a reduction in the activity of the P2X receptor pathway. Qin, L., Li, Q., Li, J.[2021]

A pilot study involving 34 patients with symptomatic peripheral artery disease (PAD) found that unsupervised, home-based leg heat therapy significantly improved walking performance, with a notable increase in the 6-minute walk distance after 8 weeks compared to a sham treatment.

The leg heat therapy was shown to be safe and well-tolerated, suggesting it could be a practical and painless adjunctive treatment to enhance physical function in patients with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of home-based leg heat therapy on walking performance in patients with symptomatic peripheral artery disease: a pilot randomized trial. Monroe, JC., Pae, BJ., Kargl, C., et al.[2023]

Heated-water exercise therapy (HWET) showed significantly greater improvements in cardiovascular function, exercise tolerance, and body composition compared to land-based exercise therapy (LBET) in patients with peripheral artery disease (PAD), based on a study of 53 participants over 12 weeks.

Both HWET and LBET effectively reduced arterial stiffness and blood pressure, but HWET resulted in better outcomes for walking distance and claudication onset time, suggesting it may enhance quality of life more effectively for PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of heated water-based versus land-based exercise training on vascular function in individuals with peripheral artery disease. Park, SY., Wong, A., Son, WM., et al.[2022]

Supervised treadmill exercise significantly improves walking performance in patients with lower extremity peripheral artery disease (PAD), with a meta-analysis showing an average increase of 180 meters in maximal walking distance and 128 meters in pain-free walking distance compared to control groups.

Home-based walking exercise programs that include behavioral change techniques are also effective, improving walking ability even more than supervised treadmill exercise, providing a viable alternative for patients who cannot attend regular supervised sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Rehabilitation for Peripheral Artery Disease: A REVIEW. McDermott, MM.[2019]

A 6-week supervised leg heat therapy (HT) using water-circulating trousers did not improve walking distance or blood pressure in patients with peripheral artery disease (PAD), but it significantly enhanced perceived physical function and reduced serum endothelin-1 levels.

The study involved 32 PAD patients, with 30 completing the treatment, showing high adherence and good tolerance to HT, indicating its potential as a supportive therapy for improving quality of life in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease. Monroe, JC., Lin, C., Perkins, SM., et al.[2021]

Heat therapy (HT) significantly reduces fat accumulation and body mass in diet-induced obese mice with peripheral artery disease, showing a 25% to 29% decrease in fat mass after 2 to 3 weeks of treatment.

HT improves skeletal muscle function, specifically increasing muscle mass relative to body mass and enhancing the maximal force of certain muscles, which may benefit diabetic and obese patients with PAD who cannot engage in traditional exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heat therapy improves body composition and muscle function but does not affect capillary or collateral growth in a model of obesity and hindlimb ischemia. Kim, K., Ro, B., Damen, FW., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8358540/

A systematic review of the role of heat therapy for patients ... Results suggest that whole-body immersion and a lower-body heated garment increased limb blood flow. Pellinger et al. and Thomas et al. reported that blood flow ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468428724002600

Development and feasibility testing of a new device for ... Emerging evidence suggests that regular heat therapy (HT) may improve cardiovascular and physical function in patients with PAD. However, the lack of accessible ...

3. karger.com karger.com/jvr/article/62/4/219/926644/Heat-Therapy-as-a-Viable-Treatment-for-Peripheral

Heat Therapy as a Viable Treatment for Peripheral Artery ... Heat therapies have demonstrated similar or even superior outcomes compared to traditional exercise/walking therapies, with higher adherence ...

4. journals.physiology.org journals.physiology.org/doi/full/10.1152/ajpheart.00151.2019?doi=10.1152/ajpheart.00151.2019

Heat therapy vs. supervised exercise therapy for peripheral ... Heat therapy via hot-water immersion and supervised exercise both improved walking distance and resting blood pressure in peripheral arterial disease (PAD) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7792848/

Leg heat therapy improves perceived physical function but ... Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease.

6. karger.com karger.com/jvr/article/doi/10.1159/000546163/926644/Heat-Therapy-as-a-Viable-Treatment-for-Peripheral

Heat Therapy as a Viable Treatment for Peripheral Artery ... Heat therapy has emerged as a promising alternative, showing similar improvements in vascular and cardiovascular function, often with higher adherence rates.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12412206/

Feasibility of unsupervised, home-based leg heat therapy in ... Acute heat exposure in older adults has been shown to lower arterial blood pressure (14, 53), improve macrovascular and skeletal muscle ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06310928

The Effect of Thermal Blanket After Peripheral Artery Surgery Thermal blankets, a passive heating blanket, have a silver surface to prevent heat loss through radiation. Thermal insulation is achieved thanks to the fact ...