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

Early Phase 1
Recruiting
Conditions
PAD
Interventions
Other: Without Heating
Other: Warm Bath
Other: Heating Suit
Other: Lower limb warm water immersion
Other: Neutral Bath
Other: Gardner walking protocol
Registration Number
NCT03900832
Lead Sponsor
Milton S. Hershey Medical Center
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
32
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PAD without heatingWithout HeatingSubjects 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.
PAD without heatingGardner walking protocolSubjects 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.
Healthy subjects without heatingWithout HeatingSubjects 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.
Healthy subjects warm bathWarm BathSubjects 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.
PAD warm bathWarm BathSubjects 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.
PAD warm bathGardner walking protocolSubjects 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.
PAD neutral bathGardner walking protocolSubjects 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.
PAD heating suitHeating SuitWhole 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.
PAD heating suitGardner walking protocolWhole 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.
PAD lower limb warm water immersionLower limb warm water immersionSubjects 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.
PAD neutral bathNeutral BathSubjects 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.
Healthy subjects warm bathGardner walking protocolSubjects 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.
Healthy subjects heat suitHeating SuitWhole 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.
Healthy subjects without heatingGardner walking protocolSubjects 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.
Healthy subjects neutral bathGardner walking protocolSubjects 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.
PAD lower limb warm water immersionGardner walking protocolSubjects 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.
Healthy subjects neutral bathNeutral BathSubjects 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.
Healthy subjects lower limb immersionGardner walking protocolSubjects 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.
Healthy subjects heat suitGardner walking protocolWhole 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.
Healthy subjects lower limb immersionLower limb warm water immersionSubjects 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.
Primary Outcome Measures
NameTimeMethod
Heart Rate in beats per minuteRecorded continuously during the 3-4 hour study visit

Electrocardiogram (ECG) patches attached to a Cardiocap will monitor heart rat

Blood pressure in mmHgRecorded continuously during the 3-4 hour study visit

Cuffs placed on a finger and arm will monitor blood pressure.

Walking time in minutesRecording walking time to fatigue (up to 22 minutes maximum) during of every 3-4 hour study visit.

Walking time on treadmill using Gardner protocol

Secondary Outcome Measures
NameTimeMethod
Near infrared spectroscopy (NIRS) in arbitrary unitsRecorded continuously during the 3-4 hour study visit

This system is designed specifically for non-invasive measurements of muscle tissue. The system measures the tissue saturation of the investigated muscle, called the 'tissue saturation index' (TSI).

Internal Temperature in degrees CRecorded continuously during the 3-4 hour study visit

The internal temperature (Tcore) will be measured from the stomach/intestines via a telemetry pill swallowed by subjects.

Trial Locations

Locations (1)

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

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