Peripheral Arterial Disease
Conditions
Brief summary
The purpose of this study is to investigate whether exposure to heat therapy improves calf muscle oxygenation and enhances walking tolerance in patients with symptomatic Peripheral Arterial Disease (PAD).
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 study is to establish evidence to support the validity of HT in improving walking tolerance on PAD patents. Subjects will complete baseline assessments for eligibility, including medical history and ankle-brachial measurement. Eligible participants will be asked to report to the laboratory on 4 different occasions. The purpose of visits 1 and 2 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. is to familiarize the participants with the treadmill walking test and assess the test-retest reliability of maximal walking time determination. On visits 3 and 4 participants will receive either heat treatment or a control treatment for 80 min prior to undergoing a symptom-limited incremental test on the treadmill.
Interventions
DEVICEControl/Sham Treatment
Water at 33ºC was circulated through water-circulating trousers.
DEVICEHeat Therapy (HT)
Water at 42-43ºC was circulated through the water-circulating trousers.
Sponsors
Roseguini, Bruno, PhD
Michael Emery, MD
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subjects will not be told outright which therapy there are receiving (thermoneutral or HT) and the Cardiologist supervising the exercise test will not be told which therapy was given.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Men and women with stable symptomatic leg claudication for 6 months or longer. * Ankle brachial index \< 0.9
Exclusion criteria
* Heart Failure * COPD * Critical limb ischemia * Prior amputation * Exercise-limiting co-morbidity * Recent infrainguinal revascularization or planned during study period * Plans to change medical therapy during duration of the study * Active cancer * Chronic kidney disease * HIV positive, active HBV or HCV disease * Presence of any unsuitable comorbid clinical condition in the opinion of the PI * Peripheral neuropathy, numbness or paresthesia in the legs * Morbid obesity, BMI \> 36 or unable to fit in water-circulating pants * Open wounds or ulcers on the extremity * Unable to walk on the treadmill
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Walking Time | Immediately after exposure to a single session of heat therapy or sham treatment, up to ~20 min | Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a thumbs up signal (defined as COT), and then give a thumbs down signal when they could no longer continue with the test (defined as PWT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Claudication Onset Time | The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min | Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a thumbs up signal (defined as COT), and then give a thumbs down signal when they could no longer continue with the test (defined as PWT). |
| Peak Systolic Blood Pressure | The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min | Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer during exercise. |
| Peak Diastolic Blood Pressure | The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min | Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer prior and during exercise |
| Peak Calf Tissue Saturation Index | The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min | The tissue saturation index (TSI%) of the most symptomatic leg was assessed with a commercially available NIRS system (Portamon, Artinis Medical Systems, The Netherlands). |
| Post-exercise Plasma Endothelin-1 Concentration | The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min. Ten minutes following completion of the incremental treadmill test, blood samples were obtained for the assessment of serum ET-1 | Commercially available enzyme-linked immunosorbent assay kits were used to measure the plasma concentrations of ET-1 (DET100, Endothelin-1 Quantikine ELISA Kit, R&D Systems, Minneapolis, MN, United States) |
Countries
United States
Participant flow
Recruitment details
Participants were identified and contacted by the Indiana Clinical and Translational Science Institute Research Network (ResNet) research assistants. After interest in participation was established, patients were contacted directly by the investigators. Additional study participants were identified by physicians from the Division of Vascular Surgery at Methodist Hospital.
Pre-assignment details
Nineteen participants were consented, but three were withdrawn before receiving an experimental treatment due to the inability to safely and consistently perform the treadmill exercise test. A total of 16 participants completed all study visits.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants were assigned, using a randomized, crossover design, to undergo a single session of either a sham treatment (sham) or heat therapy (HT) prior to a symptom-limited cardiopulmonary treadmill exercise test. In the sham treatment session, water at 33°C was circulated through the trousers for 90 min using a water pump (HTP-1500, Adroit Medical, Louden, Tennessee, United States). In the HT session, water at 43℃ was circulated through the tube-lined trousers using a heated bath circulator (HT; Aqua Relief Systems, Akron, Ohio, United States) with the goal of increasing leg skin temperature to 37-38ºC. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 5.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 1 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Peak Walking Time
Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a thumbs up signal (defined as COT), and then give a thumbs down signal when they could no longer continue with the test (defined as PWT).
Time frame: Immediately after exposure to a single session of heat therapy or sham treatment, up to ~20 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Peak Walking Time | 955.6 seconds | Standard Deviation 84.3 |
| Heat Therapy | Peak Walking Time | 947.7 seconds | Standard Deviation 88.1 |
Secondary
Claudication Onset Time
Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a thumbs up signal (defined as COT), and then give a thumbs down signal when they could no longer continue with the test (defined as PWT).
Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Claudication Onset Time | 452.6 Seconds | Standard Deviation 53.2 |
| Heat Therapy | Claudication Onset Time | 442.9 Seconds | Standard Deviation 65.1 |
Secondary
Peak Calf Tissue Saturation Index
The tissue saturation index (TSI%) of the most symptomatic leg was assessed with a commercially available NIRS system (Portamon, Artinis Medical Systems, The Netherlands).
Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Peak Calf Tissue Saturation Index | 43.9 % tissue saturation | Standard Deviation 7.6 |
| Heat Therapy | Peak Calf Tissue Saturation Index | 43.1 % tissue saturation | Standard Deviation 8.2 |
Secondary
Peak Diastolic Blood Pressure
Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer prior and during exercise
Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Peak Diastolic Blood Pressure | 74.2 mmHg | Standard Deviation 9.7 |
| Heat Therapy | Peak Diastolic Blood Pressure | 73.5 mmHg | Standard Deviation 11.6 |
Secondary
Peak Systolic Blood Pressure
Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer during exercise.
Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Peak Systolic Blood Pressure | 193.3 mmHg | Standard Deviation 23.2 |
| Heat Therapy | Peak Systolic Blood Pressure | 189.3 mmHg | Standard Deviation 31 |
Secondary
Post-exercise Plasma Endothelin-1 Concentration
Commercially available enzyme-linked immunosorbent assay kits were used to measure the plasma concentrations of ET-1 (DET100, Endothelin-1 Quantikine ELISA Kit, R&D Systems, Minneapolis, MN, United States)
Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min. Ten minutes following completion of the incremental treadmill test, blood samples were obtained for the assessment of serum ET-1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Treatment | Post-exercise Plasma Endothelin-1 Concentration | 2.0 pg/mL | Standard Deviation 0.6 |
| Heat Therapy | Post-exercise Plasma Endothelin-1 Concentration | 1.7 pg/mL | Standard Deviation 0.5 |