Clinical trial NCT02770547: Leg Thermotherapy for Intermittent Claudication
Official title: Leg Thermotherapy for Intermittent Claudication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Artery Disease
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2016-05-12
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Exercise Tolerance Assessed by Measuring Distance (m) Walked in 6-minutes
timeFrame: Maximal walking distances on a 6mwt were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.
measure: Blood Pressure
timeFrame: 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.
measure: Circulating Levels of Endothelin-1 (pg/mL)
timeFrame: Serum endothelin-1 levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.
measure: Circulating Total Nitrate Levels (mmol)
timeFrame: Serum total nitrate levels were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.
Secondary outcomes:
measure: Vascular Function Assessed by Leg MRI to Measure Peak Blood Flow in Popliteal Artery (ml/s)
timeFrame: Peak flows after post-occlusive reactive hyperemia were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.
measure: 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)
timeFrame: Ankle-brachial index measures were obtained at weeks 3/6 and 6/6 of the study and compared to baseline values.
measure: Vascular Function Measuring Leg Cutaneous Vascular Conductance - Measured by Laser-doppler Flowmetry of the Skin
timeFrame: 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.
measure: Patient Reported Functional Health and Well-being Using 36-item Short Form Health Survey
timeFrame: SF-36 questionnaires were administered at weeks 3/6 and 6/6 of the study and compared to baseline values.
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center
state: Indiana
Study officials:
affiliation: Purdue University
name: Bruno Tesini Roseguini, PhD
role: STUDY_DIRECTOR
References: