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

32 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment for Peripheral Artery Disease?

Research shows that heat therapy, such as heated-water exercise and home-based leg heating, can improve walking distance and reduce blood pressure in patients with Peripheral Artery Disease (PAD). These therapies are well-tolerated and can enhance exercise tolerance and quality of life, making them a promising alternative or complement to traditional exercise programs. ^{1 2 3 4 5}

Is heat therapy safe for humans with peripheral artery disease?

Heat therapy, such as hot-water immersion and heated-water exercise, has been well tolerated and shown to be safe in studies involving patients with peripheral artery disease. Participants adhered well to the treatment, and no significant safety concerns were reported. ^{2 3 6 7 8}

How does the No Heat Treatment for Peripheral Artery Disease differ from other treatments?

The No Heat Treatment, or Standard Exercise Protocol, for Peripheral Artery Disease (PAD) involves supervised exercise without additional heating elements. Unlike heat therapies that use hot-water immersion or heated garments to improve blood flow and reduce symptoms, this approach focuses solely on traditional exercise to enhance walking ability and cardiovascular health. ^{1 2 3 7 8}

What is the purpose of this trial?

The study objectives of this projects are to examine the hypothesis that the sympathetic and blood pressure responses to exercise will be attenuated during and after heat exposure in patients with peripheral artery disease, via altering the sensitivity of the muscle afferent receptors.

Research Team

Jian Cui

Principal Investigator

Penn State College of Medicine

Eligibility Criteria

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 had heart issues like unstable angina or a heart attack in the last 6 months.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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 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]

References

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

Acute Lower Leg Heating Increases Exercise Capacity in Patients With Peripheral Artery Disease. [2020]

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

Heat therapy vs. supervised exercise therapy for peripheral arterial disease: a 12-wk randomized, controlled trial. [2020]

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

Effects of heated water-based versus land-based exercise training on vascular function in individuals with peripheral artery disease. [2022]

4. United States 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. [2023]

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

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

6. United States 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. [2022]

7. United States 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. [2021]

8. England 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. [2021]