Effects of Heating on Exercise Pressor Reflex in Peripheral Artery Disease: Exercise Ability (EPR)

Penn State Health

Status and phase: Completed; Early Phase 1

Conditions: PAD

Treatments: Other: Heating Suit; Other: Gardner walking protocol; Other: Warm Bath; Other: Lower limb warm water immersion; Other: Neutral Bath; Other: Without Heating

Study type: Interventional

Funder types: Other

Identifiers

NCT03900832

STUDY00005798

Details and patient eligibility

About

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.

Full description

Peripheral arterial disease (PAD) affects 8-12 million Americans and its cardinal symptom is leg pain during exercise, termed "intermittent claudication". The diagnosis of PAD involves measuring the ankle-brachial index (ABI, i.e. the systolic pressure in the ankle divided by the systolic pressure in the arm); values below 0.9 are indicative of large vessel obstruction. Intermittent claudication is the most common symptom of this disease and it regularly occurs during exercise/physical activity but is relieved promptly by rest. Previous studies suggest that as the exercise pressor reflex is activated in patients with PAD, BP and heart rate (HR) are exaggerated. The BP rises during walking in the PAD patients were significantly greater than that seen in healthy control subjects. A recent human study from our group further indicates that an early BP response occurred during plantar flexion exercise before claudication was noted by the subjects, which may suggest that the accentuated BP response was due to an augmented muscle mechanoreflex in PAD. Moreover, another recent study from our group also showed that PAD patients have augmented renal vasoconstriction during plantar flexion exercise.

It has been shown that exercise has benefits for patients with PAD. However, exercise becomes limited due to the pain and fatigue associated with the disease. Moreover, the augmented pressor response to exercise in PAD may increase the risk for the end organ damage (e.g. brain and/or heart). Thus, finding alternate/complimentary interventions that modulate the cardiovascular system and autonomic nervous system, and can be tolerated by the patients, would be beneficial.

One possible intervention is heat exposure, since acute bouts of exercise and acute heat exposure have similar acute effects on both the autonomic and cardiovascular systems. For example, both exercise and heat exposure increase body temperature, increase HR, increase cardiac output (CO), increase left ventricular ejection fraction (EF), and enhance myocardial function. In the peripheral circulation, both exercise and heat exposure increase limb blood flow , muscle blood flow, and skin blood flow. Moreover, recent studies suggest that whole body exposure improves the endothelium function in PAD patients (e.g. activates endothelial progenitor cells CD34+).

However, the effect of heat treatment on the ability of walking of PAD patients has not been examined. Moreover, it is unknown if heating can normalize/decrease the accentuated the pressor responses to exercise in PAD patients.

Enrollment: 33 patients

Sex: All

Ages: 21 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

All subjects

• Capable of giving informed consent
• Any race or ethnicity
• Men and women age 21- 85 years (inclusive)
• Fluent in written and spoken English

Patients with peripheral arterial disease (PAD)

• Diagnosed with PAD (i.e., ankle-brachial index below 0.9)
• Fontaine stage II or less - no pain while resting
• Satisfactory history and physical exam

Healthy subjects

• Satisfactory history and physical examination
• Free of acute medical conditions

Exclusion criteria

For patients with PAD and Healthy subjects

• Age < 21 years
• Pregnant or nursing women
• Decisional impairment
• Prisoners

For patients with PAD

• History of CAD with symptoms of unstable angina or myocardial infarction (<6 months)
• History of epilepsy or seizure disorders

For healthy subjects

• Any other chronic diseases (heart, lung, neuromuscular disease or diabetes)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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33 participants in 10 patient groups, including a placebo group

PAD without heating

Placebo Comparator group

Description:

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.

Treatment:

Other: Without Heating

Other: Gardner walking protocol

PAD warm bath

Experimental group

Description:

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.

Treatment:

Other: Warm Bath

Other: Gardner walking protocol

PAD neutral bath

Placebo Comparator group

Description:

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.

Treatment:

Other: Neutral Bath

Other: Gardner walking protocol

PAD heating suit

Experimental group

Description:

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.

Treatment:

Other: Gardner walking protocol

Other: Heating Suit

PAD lower limb warm water immersion

Experimental group

Description:

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.

Treatment:

Other: Lower limb warm water immersion

Other: Gardner walking protocol

Healthy subjects without heating

Placebo Comparator group

Description:

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.

Treatment:

Other: Without Heating

Other: Gardner walking protocol

Healthy subjects warm bath

Experimental group

Description:

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.

Treatment:

Other: Warm Bath

Other: Gardner walking protocol

Healthy subjects neutral bath

Placebo Comparator group

Description:

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.

Treatment:

Other: Neutral Bath

Other: Gardner walking protocol

Healthy subjects heat suit

Experimental group

Description:

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.

Treatment:

Other: Gardner walking protocol

Other: Heating Suit

Healthy subjects lower limb immersion

Experimental group

Description:

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.

Treatment:

Other: Lower limb warm water immersion

Other: Gardner walking protocol