Peripheral Arterial Disease
Conditions
Brief summary
The objective of this study is to evaluate the benefits of participating for 8 weeks in a home-based daily treatment with heat therapy (HT) or a thermoneutral control intervention, as assessed by vascular function, walking tolerance and quality of life.
Detailed description
Heat therapy (HT) is an emerging non-invasive approach that has been shown to enhance vascular function of the leg in old individuals. The objective of this randomized, controlled study is to evaluate the benefits of participating for 8 weeks in a home-based daily treatment with heat therapy (HT) or a thermoneutral control intervention, as assessed by vascular function, walking tolerance and quality of life. The central hypothesis of this study, based on preliminary data, is that exposure to HT will enhance the oxygenation of calf muscles during exercise and as a result, the onset of pain will be delayed and walking performance will be enhanced. The duration (8 weeks) was chosen based on the recent report of Brunt and co-workers that the improvement in endothelial function promoted by repeat HT in sedentary individuals peaks at 8 weeks following the onset of treatment. Heat Therapy will be applied daily for 90 minutes using water-circulating 'pants' connected to a water pump. Outcomes will be assessed at the halfway point (end of week 4), at the completion of the intervention (end of week 8) and 4 weeks after the end of the intervention (week 12).
Interventions
DEVICEControl/Sham Treatment
Thermoneutral water will be circulated through water-circulating trousers to maintain skin temperature at baselines levels daily for 90 minutes for 8 weeks.
DEVICEHeat Therapy
Water at 110 degrees F will be circulated through water-circulating trousers daily for 90 minutes for 8 weeks.
Sponsors
Roseguini, Bruno, PhD
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants were informed that there were two different categories of heat therapy, low heat and high heat, and that both might be beneficial for claudication symptoms.
Intervention model description
Patients were randomized (blocked and stratified by sex) using assignments generated from PROC PLAN in SAS Version 9.4 by the study statistician into one of two groups: those receiving leg heat therapy or those receiving the sham treatment.
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men and women with a stable symptomatic PAD for ≥6 months * Ankle brachial index \<0.9 in at least one leg * Age between 40 and 80 years
Exclusion criteria
* Uncontrolled Diabetes (HbA1C \> 8.5 measured within 3 months prior to date of consent) * Wheelchair bound * Use of a walking aid (i.e. cane, crutches, walker, motorized chair) * Critical limb ischemia (ischemic rest pain or ischemia-related non healing wounds or tissue loss * Impaired thermal sensation in the legs * Exercise-limiting comorbidity * Chronic Heart Failure stages C and stage D (Stage C: structural heart disease is present and symptoms have occurred; Stage D: presence of advanced heart disease with continued heart failure symptoms requiring aggressive medical therapy) * Morbid obesity BMI \> 35 or unable to fit into water-circulating pants * Open wounds or ulcers on the extremity * Prior amputation * Lower extremity revascularization, major orthopedic surgery, cardiovascular event, or coronary revascularization in the previous three months * Planned revascularization or major surgery during the next six months * Plans to change medical therapy during the duration of the study * Active treatment for cancer * Chronic kidney disease (eGFR \<30 by MDRD or Mayo or Cockcroft-Gault formula). * HIV positive, active HBV or HCV disease. * Presence of any clinical condition that makes the patient not suitable to participate in the trial. * Unable to walk on the treadmill
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-min Walk Distance | 8 weeks | Change in 6-min walk distance from baseline to the 8-week follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Treadmill Peak Walking Time | 8 weeks | Change in treadmill peak walking time from baseline to 8-week follow-up |
| Change in Peak Calf Blood Flow | 8 weeks | Change in peak calf blood flow during reactive hyperemia from baseline to the 8-week follow-up |
| Change in Leg Cutaneous Vascular Conductance | 8 weeks | Change in cutaneous vascular conductance from baseline to the 8-week follow-up |
| Change in the Vascular Quality of Life Questionnaire-6 Score | 8 weeks | Change in Vascular Quality of Life Questionnaire-6 score from baseline to the 8-week follow-up. The total VASCUQOL score is the average score of questions answered and ranges from 1 (worst QOL) to 7 (best QOL) |
| Change in the Short Form 36 Physical Functioning Score | 8 weeks | Change in the physical functioning subscale score from baseline to the 8-week follow-up. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. A high score defines a more favorable health state. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited by referral from the peripheral vascular disease clinic at the Department of Vascular Surgery at Indiana University's Methodist Hospital, the Non-Invasive Vascular Laboratory at Methodist Hospital, and direct participant contact by the Indiana CTSI Research Network (ResNet) office. The first participant was randomized on January 14, 2019. Final follow-up occurred on June 21, 2021.
Pre-assignment details
A total of 542 patients were referred and screened for the study. Four hundred and twenty-eight participants were deemed ineligible and 80 refused to participate. The remaining 34 patients were randomly allocated to receive HT (n = 18) or the control treatment (n = 16).
Participants by arm
| Arm | Count |
|---|---|
| Sham Participants will be dressed in water-circulating trousers that are connected to a pump. Water at 33 degrees Celsius will be circulated through the pants for 90 minutes daily for 8 weeks. | 15 |
| Heat Therapy Participants will be dressed in water-circulating trousers that are connected to a pump. Water at 43 degrees Celsius will be circulated through the pants for 90 minutes daily for 8 weeks. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance | 0 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Heat Therapy | Total | Sham |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.9 | 65.9 years STANDARD_DEVIATION 7.99 | 68.9 years STANDARD_DEVIATION 5.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 22 Participants | 12 Participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 18 |
| other Total, other adverse events | 0 / 16 | 4 / 18 |
| serious Total, serious adverse events | 0 / 16 | 0 / 18 |
Outcome results
Primary
Change in 6-min Walk Distance
Change in 6-min walk distance from baseline to the 8-week follow-up
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham | Change in 6-min Walk Distance | -0.9 meters |
| Heat Therapy | Change in 6-min Walk Distance | 21.3 meters |
Secondary
Change in Leg Cutaneous Vascular Conductance
Change in cutaneous vascular conductance from baseline to the 8-week follow-up
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham | Change in Leg Cutaneous Vascular Conductance | -2.6 percentage of maximal cutaneous vascular | Standard Deviation 13.9 |
| Heat Therapy | Change in Leg Cutaneous Vascular Conductance | -0.7 percentage of maximal cutaneous vascular | Standard Deviation 16.3 |
Secondary
Change in Peak Calf Blood Flow
Change in peak calf blood flow during reactive hyperemia from baseline to the 8-week follow-up
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham | Change in Peak Calf Blood Flow | -4.8 mL/min/100 g | Standard Deviation 21.9 |
| Heat Therapy | Change in Peak Calf Blood Flow | -2.8 mL/min/100 g | Standard Deviation 11 |
Secondary
Change in the Short Form 36 Physical Functioning Score
Change in the physical functioning subscale score from baseline to the 8-week follow-up. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. A high score defines a more favorable health state.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham | Change in the Short Form 36 Physical Functioning Score | 4.5 score on a scale | Standard Deviation 10.8 |
| Heat Therapy | Change in the Short Form 36 Physical Functioning Score | 4.5 score on a scale | Standard Deviation 15.9 |
Secondary
Change in the Vascular Quality of Life Questionnaire-6 Score
Change in Vascular Quality of Life Questionnaire-6 score from baseline to the 8-week follow-up. The total VASCUQOL score is the average score of questions answered and ranges from 1 (worst QOL) to 7 (best QOL)
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham | Change in the Vascular Quality of Life Questionnaire-6 Score | 0.6 score on a scale | Standard Deviation 0.8 |
| Heat Therapy | Change in the Vascular Quality of Life Questionnaire-6 Score | 0.5 score on a scale | Standard Deviation 0.6 |
Secondary
Change in Treadmill Peak Walking Time
Change in treadmill peak walking time from baseline to 8-week follow-up
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham | Change in Treadmill Peak Walking Time | 61.5 seconds | Standard Deviation 111.2 |
| Heat Therapy | Change in Treadmill Peak Walking Time | 109.5 seconds | Standard Deviation 85.4 |