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

NCT03900832 | Completed Early Phase 1

• 1 other identifier: STUDY00005798
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

PAD

Keywords

exercise; blood pressure response; heating

Outcome Measures

Primary Outcomes (3)

• Walking time in minutes

  Walking time on treadmill using Gardner protocol

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

• Blood pressure in mmHg

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

  Recorded continuously during the 3-4 hour study visit

• Heart Rate in beats per minute

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

  Recorded continuously during the 3-4 hour study visit

Secondary Outcomes (2)

• Internal Temperature in degrees C

  Recorded continuously during the 3-4 hour study visit

• Near infrared spectroscopy (NIRS) in arbitrary units

  Recorded continuously during the 3-4 hour study visit

Study Arms (10)

PAD without heating

PLACEBO COMPARATOR

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.

Other: Without Heating; Other: Gardner walking protocol

PAD warm bath

EXPERIMENTAL

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.

Other: Warm Bath; Other: Gardner walking protocol

PAD neutral bath

PLACEBO COMPARATOR

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.

Other: Neutral Bath; Other: Gardner walking protocol

PAD heating suit

EXPERIMENTAL

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.

Other: Heating Suit; Other: Gardner walking protocol

PAD lower limb warm water immersion

EXPERIMENTAL

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.

Other: Lower limb warm water immersion; Other: Gardner walking protocol

Healthy subjects without heating

PLACEBO COMPARATOR

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.

Other: Without Heating; Other: Gardner walking protocol

Healthy subjects warm bath

EXPERIMENTAL

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.

Other: Warm Bath; Other: Gardner walking protocol

Healthy subjects neutral bath

PLACEBO COMPARATOR

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.

Other: Neutral Bath; Other: Gardner walking protocol

Healthy subjects heat suit

EXPERIMENTAL

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.

Other: Heating Suit; Other: Gardner walking protocol

Healthy subjects lower limb immersion

EXPERIMENTAL

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.

Other: Lower limb warm water immersion; Other: Gardner walking protocol

Interventions

Without Heating OTHER

Subject will complete walking protocol without any heating procedure

Healthy subjects without heating; PAD without heating

Warm Bath OTHER

Subjects will sit in a warm bathtub with water up to their shoulders, while one arm will be out of water for BP and HR measurement. The water temperature and internal temperature (Tcore), BP and HR will be measured throughout the bath. The water temperature will be controlled between 38-41°C. Subjects will remain in the tub for ≤ 30 minutes. If the HR increases more than 15 -20 bpm, or a significant BP drop occurs (e.g. BP \>20 mmHg), the subject will be removed from the bath even if the time is \<30 min.

Healthy subjects warm bath; PAD warm bath

Neutral Bath OTHER

Subjects will sit in a warm bathtub with water up to their shoulders, while one arm will be out of water for BP and HR measurement. The water temperature and internal temperature (Tcore), BP and HR will be measured throughout the bath. The water temperature will be controlled between 35 - 37°C. Subjects will remain in the tub for ≤ 30 minutes.

Healthy subjects neutral bath; PAD neutral bath

Heating Suit OTHER

The mean skin temperature Tsk will be controlled with a water-perfused suit worn by subjects. Whole-body heating will be accomplished by perfusing warm water (\~ 45 - 50 °C) through the suit to elevate the Tsk to ≤ 38 °C (100 oF). Warm water is through plastic tubes, and subjects' skin will not directly touch warm water. The heating will be continued until the ∆Tcore reaches \~ 0. 6 - 1.0 °C. This may take approximately 60 - 90 min.

Healthy subjects heat suit; PAD heating suit

Lower limb warm water immersion OTHER

Subjects will sit on a chair and put their lower legs and feet in a bucket with warm water. The water level will be just below the knees (depth of approximately 40 cm). The water temperature will be monitored and controlled at \~38 - 42 °C throughout the 30 minutes. BP, HR, Tcore, the skin temperature and skin blood flow (e.g. on a thigh and/or forearm) will be measured before, during and after the lower limbs warm water immersion.

Healthy subjects lower limb immersion; PAD lower limb warm water immersion

Gardner walking protocol OTHER

The Gardner protocol begins at 2 mph and 0% grade for 2 minutes. The grade increases by 2% every 2 minutes (the speed remains 2 mph) until the subject says they want to stop or 22 minutes maximum. BP and HR will also be measured throughout the protocol.

Healthy subjects heat suit; Healthy subjects lower limb immersion; Healthy subjects neutral bath; Healthy subjects warm bath; Healthy subjects without heating; PAD heating suit; PAD lower limb warm water immersion; PAD neutral bath; PAD warm bath; PAD without heating

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (4)

• Cui J, Blaha C, Sinoway LI. Whole body heat stress attenuates the pressure response to muscle metaboreceptor stimulation in humans. J Appl Physiol (1985). 2016 Nov 1;121(5):1178-1186. doi: 10.1152/japplphysiol.00212.2016. Epub 2016 Oct 7.

  PMID: 27763873 BACKGROUND

• Cui J, Blaha C, Moradkhan R, Gray KS, Sinoway LI. Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans. J Physiol. 2006 Oct 15;576(Pt 2):625-34. doi: 10.1113/jphysiol.2006.116640. Epub 2006 Jul 27.

  PMID: 16873399 BACKGROUND

• Cui J, Boehmer J, Blaha C, Sinoway LI. Muscle sympathetic nerve activity response to heat stress is attenuated in chronic heart failure patients. Am J Physiol Regul Integr Comp Physiol. 2017 Jun 1;312(6):R873-R882. doi: 10.1152/ajpregu.00355.2016. Epub 2017 Mar 22.

  PMID: 28330967 BACKGROUND

• Cui J, Muller MD, Blaha C, Kunselman AR, Sinoway LI. Seasonal variation in muscle sympathetic nerve activity. Physiol Rep. 2015 Aug;3(8):e12492. doi: 10.14814/phy2.12492.

  PMID: 26265752 BACKGROUND

MeSH Terms

Conditions

Motor Activity

Interventions

Heating

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Environment, Controlled; Environment; Environment and Public Health

Study Officials

• Jian Cui

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Subjects will be aware if they are being heated or not, but data analysis process is blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: The investigators will examine (using a prospective observational design) if heating will affect walking ability, blood pressure and heart rate responses in PAD patients. Each subject will serve as their own control. Additionally, we will compare these responses between PAD patients and healthy controls subjects.

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 3, 2019
• Study Start: May 15, 2019
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)