A New Heat Therapy Device for Home-based Leg Heating in Patients With Lower-extremity Peripheral Artery Disease: a Pilot Study
Phase: PHASE1
Conditions: Peripheral Arterial Disease, Intermittent Claudication
Sponsor: Purdue University

 
A New Heat Therapy Device for Home-based Leg Heating in Patients With Lower-
extremity Peripheral Artery Disease 
 
NCT05335161 
 
February 22, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

1. Background and Rationale 
 
Peripheral artery disease (PAD) is a chronic condition characterized by impaired blood flow to the 
lower extremities. It is prevalent in older adults and is associated with mobility impairment, pain, 
and increased risk of cardiovascular events. Previous studies have suggested that heat therapy may 
improve vascular function and limb perfusion in patients with PAD. This study aims to develop 
and test the feasibility of a novel home-based leg heat therapy system specifically designed for 
patients with lower extremity PAD. 
 
2. Objectives 
 
The primary goal of this study is to design a clinical-grade, easy-to-use leg HT system for elderly 
individuals suffering from PAD. Building on an existing cryotherapy water-circulating device 
designed for sports recovery, we will develop a new prototype system consisting of leg sleeves 
composed of an inner layer of polyurethane water-circulating pads and an outer layer of six 
inflatable bladders. The feasibility and safety of the prototype units will be evaluated in a single-
arm pilot trial involving six patients with symptomatic PAD. The primary outcomes are completion 
rates, safety, and device usability. Secondary outcomes included changes in 6-minute walk 
distance, calf strength, performance on the five times sit-to-stand test, and quality of life as 
measured by the Walking Impairment Questionnaire (WIQ). 
 
3. Participants 
 
Patients with symptomatic PAD will be recruited through flyers, online advertisements, and 
referrals from local peripheral vascular disease clinics. Men and women 60 years or older with a 
resting ABI of ≤0.90 in at least one leg were included in the study. Individuals with a resting ABI 
of >0.91 at baseline will be eligible if their ABI decreases by ≥20% after a heel-rise test. The 
exclusion criteria include the presence of critical limb ischemia (ischemic rest pain or ischemia-
related, nonhealing wounds, or tissue loss), prior leg amputation, exercise tolerance limited by 
factors other than leg pain (eg, angina, arthritis, severe lung disease, etc), recent lower extremity 
revascularization or orthopedic surgery, use of a walking aid other than a cane, active cancer, 
chronic kidney disease (estimated glomerular filtration rate of <30), inability to fit into water-
circulating trousers, a Mini-Mental Status Examination score of <23, and impaired thermal 
sensation in the leg. 
 
 
4. Experimental protocol 
 
Participants will attend two baseline laboratory visits. Before each session, they will be instructed 
to fast overnight, avoid exercise for 24 hours, and refrain from smoking for 4 hours. During the 
first visit, participants will receive informed consent, complete a medical history form, have their 
leg symptoms assessed using the San Diego Claudication Questionnaire, complete the Mini-
Mental Status Examination, and undergo a thermal sensation test with heating pads on their thighs 
and calves. The ABI will be assessed following American Heart Association guidelines. After a 
10-minute rest, a handheld Doppler ultrasound probe will be used to measure systolic pressures in 
the posterior tibial, dorsalis pedis, and brachial arteries. The ABI for each leg will be calculated 

by dividing the average dorsalis pedis and posterior tibial pressures by the average brachial 
pressures. Participants will then be familiarized with the 6-minute walk test, isokinetic calf strength 
testing, and the five-times sit-to-stand test. 
The second visit, conducted at least 48 hours later, will include (1) blood pressure 
measurement, (2) a 6-minute walk test, (3) torque assessments of the plantar flexors using an 
isokinetic dynamometer, (4) the five-times sit-to-stand test, and (5) quality of life assessment via 
the WIQ. After completing baseline tests, participants will undergo a supervised 90-minute 
treatment session with the prototype HT device to monitor acute changes in skin temperature and 
blood pressure. Thermocouples (MLT422; AD Instruments, Colorado Springs, CO) will be taped 
to the calf and thigh to measure leg skin temperature, and systolic and diastolic blood pressures 
will be recorded every 5 minutes. 
Participants will be given the prototype device for daily use while lying down or seated 
with legs extended. They will log therapy sessions and measure blood pressure before and after 
each session using a portable monitor (Omron 3 Series Upper arm, Omron Healthcare Co. Ltd., 
Kyoto, Japan). Weekly check-ins with the study coordinator will track therapy dates, times, blood 
pressure readings, and any adverse effects. Outcomes will be reassessed at the end of the 12-week 
intervention, with participants stopping treatment 48 hours before the final evaluations to isolate 
chronic effects. 
 
 
5. Outcome measures 
 
Feasibility end points (primary outcomes) 
 
The completion rate will be determined by monitoring the number of participants who finish the 
study protocol within the specified timeframe compared to the total number enrolled in the study. 
 
Safety: Safety will be evaluated by monitoring adverse events. The research coordinator will call 
patients weekly to record any adverse events during the intervention. 
 
Device usability: Participants will be asked to rate the device usability at the end of the experiment 
using the System Usability Scale. The psychometric properties of the System Usability Scale have 
been established, including its reliability and sensitivity. 
 
Secondary outcomes 
 
6-Minute walk test: Participants will receive standardized instructions and be asked to walk the 
greatest distance possible by walking back and forth along a 100-ft corridor for 6 minutes.  
 
Blood pressure: Blood pressure measurement will be conducted using an automated device 
(Tango+, Suntech Medical, Morrisville, NC), following the recommendations of the American 
Heart Association.  
 
Calf strength: Torque assessments of the plantar flexors of the most symptomatic leg or the leg 
with the lowest ABI will be conducted using an isokinetic dynamometer (Biodex System 4 Pro, 
Biodex Medical Systems, Shirley, NY). The participants will be positioned supine on the 

dynamometer chair with their knees flexed at 90°. Before maximal testing, they will complete a 
standardized warm-up consisting of three submaximal contractions, each held for 5 seconds at 
approximately 50% of perceived maximal effort. Following the warm-up, participants will perform 
three maximal voluntary isometric contractions, each lasting 5 seconds, with a 60-second rest 
period between attempts to minimize fatigue. Standardized verbal encouragement will be provided 
during each maximal voluntary isometric contraction to ensure maximal effort. The trial that 
produces the highest peak torque value (in N·m) will be selected for analysis. 
 
The Five Times Sit-to-Stand Test: Participants are asked to sit in a chair with arms folded across 
their chest and stand five times in a row as quickly as they can. The time it takes to complete five 
chair rises is recorded. 
 
WIQ: Patient-reported perceptions of walking ability will be assessed using the WIQ. This disease-
specific questionnaire assesses the ability of patients with PAD to walk defined distances and 
speeds and to climb stairs, with scores ranging from 0 to 100.30 Higher scores reflect better 
community-based walking ability. 
 
6. Statistical analysis 
This small pilot trial aims to test prototype HT devices and evaluate their safety and feasibility in 
patients with PAD. The main goal is to gather initial data to refine device design and guide the 
development of future large-scale studies. Due to the exploratory nature of this trial, no power 
analysis was performed. Changes in each outcome from baseline to the 12-week follow-up will be 
compared using paired two-sample t-tests. A two-sided P value of <.05 will be regarded as 
statistically significant. Before starting the intervention, participants will undergo a supervised HT 
session, during which skin temperature and blood pressure will be monitored every 5 minutes 
throughout the 90-minute session. Skin temperature and blood pressure responses during this 
session will be analyzed using repeated-measures analysis of variance. When a significant main 
effect is found, Sidak multiple comparisons tests will evaluate differences between time points 
relative to baseline. A P value of <.0028 will be considered statistically significant for the Sidak-
adjusted comparisons. All statistical analyses will be conducted using Prism 10 (Version 10.3.0 
(461)).