PADEarly Phase 1EPRNCT03900832
Effects of Heating on Exercise Pressor Reflex in Peripheral Artery Disease: Exercise Ability
A Early Phase 1 study testing Without Heating, Warm Bath and Neutral Bath in people with PAD, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- PAD
- What is being tested?
- Without Heating, Warm Bath and Neutral Bath
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2019to 31 Jul 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- 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
Who cannot join
- For patients with PAD and Healthy subjects
- Age < 21 years
- Pregnant or nursing women
- Decisional impairment
- Prisoners
- For patients with PAD
Show all 10Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
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.
Read the 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.
- Conditions
- PAD
- Being tested
- Without Heating, Warm Bath, Neutral Bath, Heating Suit, Lower limb warm water immersion
- Keywords
- exercise, blood pressure response, heating
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Without HeatingOther
Subject will complete walking protocol without any heating procedure
Warm BathOther
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.
Neutral BathOther
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.
Heating SuitOther
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.
Lower limb warm water immersionOther
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.
Gardner walking protocolOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Lower limb warm water immersion; Other: Gardner walking protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Walking time in minutes
Walking time on treadmill using Gardner protocol
Measured: 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.
Measured: 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
Measured: Recorded continuously during the 3-4 hour study visit
Secondary outcomes (2)
Internal Temperature in degrees C
The internal temperature (Tcore) will be measured from the stomach/intestines via a telemetry pill swallowed by subjects.
Measured: Recorded continuously during the 3-4 hour study visit
Near infrared spectroscopy (NIRS) in arbitrary units
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).
Measured: Recorded continuously during the 3-4 hour study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start15 May 2019
- Primary completion31 Jul 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PADStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Cui, Milton S. Hershey Medical Center
- Investigators
- Jian Cui, Principal investigator, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03900832
- Sponsor's protocol ID
- STUDY00005798
- Acronym
- EPR
- Status last verified
- Sep 2025
- First submitted
- 29 Mar 2019
- Last updated
- 16 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27763873Cui 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.
PubMed 16873399Cui 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.
PubMed 28330967Cui 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.
PubMed 26265752
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Heating on Exercise Pressor Reflex in Peripheral Artery Disease: Exercise Ability
- ClinicalTrials.gov ID
- NCT03900832
- Acronym / sponsor ID
- EPR / STUDY00005798
- Conditions
- PAD
- Keywords
- exercise, blood pressure response, heating
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- 15 May 2019 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 3 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 10
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| PAD without heating | Placebo comparator | Other: Without Heating, Other: Gardner 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. |
| PAD warm bath | Experimental | Other: Warm Bath, Other: Gardner 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 bath | Placebo comparator | Other: Neutral Bath, Other: Gardner 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 suit | Experimental | Other: Heating Suit, Other: Gardner 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 immersion | Experimental | Other: Lower limb warm water immersion, Other: Gardner 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 without heating | Placebo comparator | Other: Without Heating, Other: Gardner 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 warm bath | Experimental | Other: Warm Bath, Other: Gardner 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 neutral bath | Placebo comparator | Other: Neutral Bath, Other: Gardner 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. |
| Healthy subjects heat suit | Experimental | Other: Heating Suit, Other: Gardner 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 immersion | Experimental | Other: Lower limb warm water immersion, Other: Gardner 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. |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (10 listed)
- For patients with PAD and Healthy subjects
- Age < 21 years
- Pregnant or nursing women
- Decisional impairment
- Prisoners
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Without HeatingSubject will complete walking protocol without any heating procedure | Other | Healthy subjects without heating, PAD without heating |
| Warm BathSubjects 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. | Other | Healthy subjects warm bath, PAD warm bath |
| Neutral BathSubjects 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. | Other | Healthy subjects neutral bath, PAD neutral bath |
| Heating SuitThe 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. | Other | Healthy subjects heat suit, PAD heating suit |
| Lower limb warm water immersionSubjects 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. | Other | Healthy subjects lower limb immersion, PAD lower limb warm water immersion |
| Gardner walking protocolThe 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. | Other | 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 |
Primary outcome
Walking time in minutes
Time frame: Recording walking time to fatigue (up to 22 minutes maximum) during of every 3-4 hour study visit.
Walking time on treadmill using Gardner protocol
Blood pressure in mmHg
Time frame: Recorded continuously during the 3-4 hour study visit
Cuffs placed on a finger and arm will monitor blood pressure.
Heart Rate in beats per minute
Time frame: Recorded continuously during the 3-4 hour study visit
Electrocardiogram (ECG) patches attached to a Cardiocap will monitor heart rat
2 secondary outcomes
Internal Temperature in degrees C
Time frame: Recorded continuously during the 3-4 hour study visit
Near infrared spectroscopy (NIRS) in arbitrary units
Time frame: Recorded continuously during the 3-4 hour study visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Background: PubMed 27763873Cui 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.
- Background: PubMed 16873399Cui 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.
- Background: PubMed 28330967Cui 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.
- Background: PubMed 26265752Cui 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jian Cui principal investigator
Penn State College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Without Heating, Warm Bath and Neutral Bath in people with PAD, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Walking time in minutes (time frame: Recording walking time to fatigue (up to 22 minutes maximum) during of every 3-4 hour study visit.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03900832, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.