Leg Thermotherapy for Intermittent Claudication

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02770547
• Collaborator: American Heart Association (Other)
• Enrollment: 32
• Locations: 2
• Arms: 2
• Actual Duration (Months): 30.5
• Patients Per Site: 16
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study proposes to evaluate the potential of leg thermotherapy as a non-pharmacological intervention that could improve the mobility and exercise tolerance of patients with intermittent claudication. Thermotherapy is a simple, easily applicable therapy that enhances exercise tolerance in patients with chronic heart failure by improving peripheral vascular endothelial function.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Artery Disease	Device: Low Heat Thermotherapy; Device: High Heat Thermotherapy	N/A

Detailed Description

Peripheral arterial disease is characterized by atherosclerotic obstruction of the arteries in the lower extremities and affects approximately 10% of individuals older than 65 years. The most common clinical presentation of peripheral arterial disease is intermittent claudication, defined as leg pain caused by insufficient blood flow during walking. Individuals with intermittent claudication have severe exercise intolerance and markedly reduced levels of daily ambulatory activity. It is estimated that up to 40 million people worldwide suffer from intermittent claudication. Despite the increasing prevalence of this condition, few medical therapies improve mobility and exercise tolerance in these patients. An urgent need remains for the development of novel, non-invasive strategies that are more widely accessible and eliminate the need for supervision and frequent traveling to a clinical facility. The study proposes to evaluate the potential of leg thermotherapy as a non-pharmacological intervention that could improve the mobility and exercise tolerance of patients with intermittent claudication.

Subjects will complete baseline assessments for eligibility and ability to do study, including medical history, quality of life assessment, ankle-brachial measurement, leg MRI, venous blood draw, assessment of vascular function, and 6-minute walk test. Treatment consists of 3 treatment sessions per week for six consecutive weeks. Subjects will be randomized to low-heat therapy or high-heat therapy. Subjects will wear water-circulating pants through which the heat therapy will be administered during the treatment sessions. Outcome measurements (same as baseline assessments) will be repeated after 9 treatment sessions and after 18 treatment sessions (at the end of the treatment period).

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Leg Thermotherapy for Intermittent Claudication
• Actual Study Start Date: May 30, 2016
• Actual Primary Completion Date: Dec 14, 2018
• Actual Study Completion Date: Dec 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low Heat Thermotherapy Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg.	Device: Low Heat Thermotherapy; Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.
Experimental: High Heat Thermotherapy High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg.	Device: High Heat Thermotherapy; Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.

Outcome Measures

Primary Outcome Measures

1. Exercise Tolerance Assessed by Measuring Distance (m) Walked in 6-minutes [Maximal walking distances on a 6mwt were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   6-minutes walk test

2. Blood Pressure [Average blood pressure taken every 5 minutes for 70 minutes was obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Participants have systolic, diastolic and mean blood pressure recording 14 times during baseline, week 3 and week 6 experimental sessions.

3. Circulating Levels of Endothelin-1 (pg/mL) [Serum endothelin-1 levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Blood draw

4. Circulating Total Nitrate Levels (mmol) [Serum total nitrate levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Blood Draw

Secondary Outcome Measures

1. Vascular Function Assessed by Leg MRI to Measure Peak Blood Flow in Popliteal Artery (ml/s) [Peak flows after post-occlusive reactive hyperemia were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Phase contrast magnetic resonance imaging was performed on the leg that the patient indicated to have the most severe claudication. An inflation cuff was placed around the thigh and inflated to 75 mmHg above resting brachial systolic pressure for 5 minutes. After 5 minutes of inflation, the cuff was release and an additional 10 minutes of imaging took place.

2. Vascular Function Measured by Ankle-brachial Index - Calculated by Dividing Higher of Posterior Tibial or Dorsalis Pedis Blood Pressure (mmHg) by Higher of Right or Left Arm Systolic Blood Pressure (mmHg) [Ankle-brachial index measures were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Ankle-brachial Index

3. Vascular Function Measuring Leg Cutaneous Vascular Conductance - Measured by Laser-doppler Flowmetry of the Skin [Maximal cutaneous vascular conductance values after 40 minutes of localized heating were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   Laser-Doppler flowmetry of skin included placement of two heating probes on the anterior portion of the lower leg. The participant sat in a semi-recumbent position for 70 minutes while the temperature of the probe progressed from 33C to 39C at minute 10 and then to 43C at minute 50. Cutaneous vascular conductance was calculated at the average red blood cell flux during the final 2 minutes of the 39C heating portion divided by the mean arterial pressure taken at that time.

4. Patient Reported Functional Health and Well-being Using 36-item Short Form Health Survey [SF-36 questionnaires were administered at weeks 3/6 and 6/6 of the study and compared to baseline values.]

   36-item Short Form Health Survey. All scales are scored 1-100, with 1 being the poorest rating and 100 being the most optimal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women with a stable symptomatic claudication for ≥6 months

• Ankle brachial index <0.9

Exclusion Criteria:

• Uncontrolled Diabetes (HbA1C > 8.5 measured within 3 months prior to date of consent)

• Heart Failure

• Chronic Obstructive Pulmonary Disease

• Critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or tissue loss

• Prior amputation

• Exercise-limiting comorbidity (i.e., angina, chronic lung disease, or arthritis)

• Recent (<3 months) infrainguinal revascularization (surgery or endovascular revascularization) or revascularization planned during study period.

• Plans to change medical therapy during the duration of the study

• Active cancer

• Chronic kidney disease (eGFR <30 by Modification of Diet in Renal Disease or Mayo or Cockcroft-Gault formula).

• HIV positive, active hepatitis B virus (HBV) or hepatitis C virus (HCV) disease.

• Presence of any clinical condition that in the opinion of the principal investigator makes the patient not suitable to participate in the trial.

• Peripheral neuropathy, numbness, or paresthesia in the legs.

• Morbid obesity BMI > 35.

• Open wounds or ulcers on the extremity.

MRI Exclusions:

• Cardiac pacemaker

• Implanted cardiac defibrillator

• Aneurysm clips

• Carotid artery vascular clamp

• Neurostimulator

• Insulin or infusion pump

• Implanted drug infusion device

• Bone growth/fusion stimulator

• Cochlear, otologic, or ear implant

• History of claustrophobia or who are unable to lie flat or who do not fit inside the bore of the scanner

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Health Methodist Hospital	Indianapolis	Indiana	United States	46202
2	Richard L. Roudebush VA Medical Center	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University
• American Heart Association

Investigators

• Study Director: Bruno Tesini Roseguini, PhD, Purdue University

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 11, 2019
• Study Protocol - Mar 30, 2018

More Information

Publications

None provided.

• Responsible Party: Raghu Motaganahalli, Associate Professor, Indiana University
• ClinicalTrials.gov Identifier: NCT02770547
• Other Study ID Numbers: 1601589496
• First Posted: May 12, 2016
• Last Update Posted: Feb 10, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Peripheral Arterial Disease; Intermittent Claudication

Study Results

Participant Flow

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Period Title: Overall Study
STARTED	16	16
COMPLETED	15	15
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy	Total
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.00 (7.80)	68.73 (8.99)	68.87 (8.27)
Sex: Female, Male (Count of Participants)
Female	3 20%	1 6.7%	4 13.3%
Male	12 80%	14 93.3%	26 86.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 13.3%	4 26.7%	6 20%
White	13 86.7%	11 73.3%	24 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.45 (7.09)	175.20 (6.71)	174.30 (6.84)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	81.38 (15.83)	85.67 (15.77)	83.45 (15.67)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.93 (4.21)	27.81 (4.11)	27.36 (4.11)
Ankle-Brachial Index (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	0.64 (0.11)	0.70 (0.11)	0.67 (0.11)
Number of Participants with Lower Limb Stents (Count of Participants)
Count of Participants [Participants]	6 40%	7 46.7%	13 43.3%
Number of Participants with Type II Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	3 20%	8 53.3%	11 36.7%
Smoker (Count of Participants)
Count of Participants [Participants]	7 46.7%	6 40%	13 43.3%
6 minute walk test distance (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	386.38 (85.08)	414.12 (109.23)	400.25 (97.23)
Maximum absolute peak blood flow (ml/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/s]	3.87 (1.89)	5.73 (3.30)	4.80 (2.78)
Serum Endothelin-1 (pg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/ml]	2.44 (0.51)	2.30 (0.49)	2.37 (0.50)
Serum Total Nitrate (uM) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [uM]	64.32 (66.33)	42.19 (25.74)	53.64 (51.32)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	149.13 (12.45)	153.54 (12.22)	151.34 (12.33)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	80.82 (10.37)	82.24 (8.85)	81.53 (9.50)
Mean Arterial Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	103.59 (9.83)	106.01 (8.82)	104.80 (9.26)
Cutaneous Vascular Conductance (Percentage of maximum conductance) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of maximum conductance]	51.91 (4.23)	56.33 (2.78)	54.12 (2.52)
SF-36 (units on a scale) [Mean (Standard Deviation) ]
Phyiscal Functioning	45.00 (26.02)	42.14 (16.14)	43.57 (21.29)
Role Physical	45.09 (30.54)	41.96 (21.01)	43.53 (25.77)
Bodily Pain	49.57 (29.87)	44.93 (14.98)	47.17 (23.07)
General Health	54.81 (20.78)	58.93 (17.85)	56.94 (19.08)
Vitality	45.54 (26.34)	50.83 (19.75)	48.28 (22.90)
Social Functioning	67.86 (26.73)	65.00 (26.81)	66.38 (26.33)
Role Emotional	70.24 (31.98)	60.71 (33.40)	65.48 (32.45)
Mental Health	77.86 (17.40)	72.00 (19.16)	74.83 (18.25)

Outcome Measures

1. Primary Outcome

Title	Exercise Tolerance Assessed by Measuring Distance (m) Walked in 6-minutes
Description	6-minutes walk test
Time Frame	Maximal walking distances on a 6mwt were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

Included all participants that completed the study.

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	15	15
Week 3	388.75 (85.08)	414.96 (109.23)
Week 6	404.29 (83.05)	419.73 (113.83)

2. Primary Outcome

Title	Blood Pressure
Description	Participants have systolic, diastolic and mean blood pressure recording 14 times during baseline, week 3 and week 6 experimental sessions.
Time Frame	Average blood pressure taken every 5 minutes for 70 minutes was obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

Includes all participants that completed the study.

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	15	15
Systolic BP Week 3	146.29 (17.08)	148.97 (12.51)
Systolic BP Week 6	149.84 (9.61)	150.21 (15.38)
Diastolic BP Week 3	79.38 (10.74)	79.72 (9.42)
Diastolic BP Week 6	80.31 (8.98)	81.44 (8.64)
Mean Arterial Pressure Week 3	101.69 (12.18)	102.81 (9.33)
Mean Arterial Pressure Week 6	103.48 (7.90)	104.36 (9.39)

3. Primary Outcome

Title	Circulating Levels of Endothelin-1 (pg/mL)
Description	Blood draw
Time Frame	Serum endothelin-1 levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

One participant was excluded as an outlier from the low heat group. One participant in the high heat group did not have blood draws

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	14	14
Endothelin-1 Week 3	2.44 (0.66)	2.11 (0.37)
Endothelin-1 Week 6	2.60 (0.69)	2.00 (0.35)

4. Primary Outcome

Title	Circulating Total Nitrate Levels (mmol)
Description	Blood Draw
Time Frame	Serum total nitrate levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

One participant was excluded as an outlier from the low heat group. One participant in the high heat group did not have blood draws

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	14	14
Total Nitrate Levels Week 3	63.62 (30.60)	47.61 (21.31)
Total Nitrate Levels Week 6	58.31 (29.30)	42.95 (19.57)

5. Secondary Outcome

Title	Vascular Function Assessed by Leg MRI to Measure Peak Blood Flow in Popliteal Artery (ml/s)
Description	Phase contrast magnetic resonance imaging was performed on the leg that the patient indicated to have the most severe claudication. An inflation cuff was placed around the thigh and inflated to 75 mmHg above resting brachial systolic pressure for 5 minutes. After 5 minutes of inflation, the cuff was release and an additional 10 minutes of imaging took place.
Time Frame	Peak flows after post-occlusive reactive hyperemia were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	7	5
Week 3	4.25 (2.54)	4.85 (1.94)
Week 6	4.49 (2.51)	5.49 (2.43)

6. Secondary Outcome

Title	Vascular Function Measured by Ankle-brachial Index - Calculated by Dividing Higher of Posterior Tibial or Dorsalis Pedis Blood Pressure (mmHg) by Higher of Right or Left Arm Systolic Blood Pressure (mmHg)
Description	Ankle-brachial Index
Time Frame	Ankle-brachial index measures were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

Includes all participants that completed the study.

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	15	15
Week 3	0.64 (0.14)	0.71 (0.13)
Week 6	0.64 (0.12)	0.71 (0.11)

7. Secondary Outcome

Title	Vascular Function Measuring Leg Cutaneous Vascular Conductance - Measured by Laser-doppler Flowmetry of the Skin
Description	Laser-Doppler flowmetry of skin included placement of two heating probes on the anterior portion of the lower leg. The participant sat in a semi-recumbent position for 70 minutes while the temperature of the probe progressed from 33C to 39C at minute 10 and then to 43C at minute 50. Cutaneous vascular conductance was calculated at the average red blood cell flux during the final 2 minutes of the 39C heating portion divided by the mean arterial pressure taken at that time.
Time Frame	Maximal cutaneous vascular conductance values after 40 minutes of localized heating were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

Includes all participants that completed the study.

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	15	15
Week 3	55.08 (3.691)	56.09 (4.892)
Week 6	54.29 (4.077)	52.66 (3.806)

8. Secondary Outcome

Title	Patient Reported Functional Health and Well-being Using 36-item Short Form Health Survey
Description	36-item Short Form Health Survey. All scales are scored 1-100, with 1 being the poorest rating and 100 being the most optimal.
Time Frame	SF-36 questionnaires were administered at weeks 3/6 and 6/6 of the study and compared to baseline values.

Outcome Measure Data

Analysis Population Description

Includes all participants that completed the study.

Arm/Group Title	Low Heat Thermotherapy	High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.	High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
Measure Participants	15	15
Physical Functioning Week 3	48.08 (27.27)	45.05 (16.59)
Physical Functioning Week 6	42.67 (29.43)	49.26 (20.20)
Role Physical Week 3	50.00 (33.46)	50.00 (24.55)
Role Physical Week 6	50.42 (31.65)	56.25 (28.84)
Bodily Pain Week 3	45.85 (21.25)	49.29 (20.60)
Bodily Pain Week 6	50.33 (22.40)	51.87 (18.28)
General Health Week 3	54.92 (13.82)	61.47 (20.20)
General Health Week 6	55.33 (18.48)	59.40 (21.67)
Vitality Week 3	50.00 (21.95)	52.08 (20.41)
Vitality Week 6	55.00 (21.80)	55.00 (22.19)
Social Functioning Week 3	79.81 (30.85)	75.00 (24.02)
Social Functioning Week 6	75.83 (27.33)	72.50 (24.64)
Role Emotinoal Week 3	80.77 (27.51)	65.00 (30.57)
Role Emotional Week 6	71.67 (29.18)	64.44 (30.12)
Mental Health Week 3	81.92 (16.90)	72.33 (16.99)
Mental Health Week 6	79.67 (14.33)	71.33 (22.71)

Adverse Events

Time Frame	Adverse event data was collected for each participant over the course of 6 weeks of treatment.
Arm/Group Title	Low Heat Thermotherapy		High Heat Thermotherapy
Arm/Group Description	Low heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies low heat to the subject's leg. Low Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies low heat to the subject's leg.		High heat thermotherapy will be applied to subject's leg. Subject will wear a garment through which heated water is circulated which in turn supplies high heat to the subject's leg. High Heat Thermotherapy: Subject will wear a High Density LCG (Liquid Circulating Garment). Water will be heated and circulated through the garment, which in turn supplies high heat to the subject's leg.
All Cause Mortality
	Low Heat Thermotherapy		High Heat Thermotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Low Heat Thermotherapy		High Heat Thermotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Surface level burn	0/16 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Low Heat Thermotherapy		High Heat Thermotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

Some PC-MRI data was unreliable or lost due to errors in the scanning HR monitor. Erroneous data sets were removed, which reduced the power for PC-MRI flow-related variables.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.