Clinical trial NCT03795103: Effect of a Neuromuscular Electrical Stimulation Program on Walking Capacity in Peripheral Artery Disease Patients
Official title: Effect of a Neuromuscular Electrical Stimulation Program on Walking Capacity in Peripheral Artery Disease Patients: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Arteriopathy
Keywords: Lower Extremity Peripheral Arterial Disease
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: AD REM TECHNOLOGY
name: Ecole Normale Supérieure de Rennes
First posted: 2019-01-07
Enrollment: 120
Sex: ALL
Minimum age (years): 41
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lower extremity peripheral arterial disease (LEPAD) is a highly prevalent chronic disease. Cardiovascular mortality of LEPAD patients at five years ranges between 18 to 30%. LEPAD is primarily caused by atherosclerosis that induces an inadequate blood flow to meet the tissues demand due to the narrowing of the arteries. An aggravation of the arterial lesions in LEPAD patients induces a worsening of patients' symptoms and a severe limitation of their walking capacity, contributing to an impairment of their quality of life.

Interventions designed to improve walking impairment may have a significant impact on the functional capacity in LEPAD patients. Lower extremity electrical stimulation is an older technique that relies on different types of electrical stimulations with different expected physiological effects on hemodynamics, skeletal muscle functions or pain pathway. The aim of the ELECTRO-PAD study is to assess the effect of a 12 weeks program of neuromuscular electrical stimulation (NMES) on the absolute walking distance (AWD) measured during a treadmill test in peripheral artery disease patients.

Detailed description: The aim of the ELECTRO-PAD study is to assess the effect of a 12 weeks program of neuromuscular electrical stimulation (NMES) on the absolute walking distance (AWD) measured during a treadmill test in peripheral artery disease patients.

Arteriopatic patients will be randomized in 2 groups :

* patients submitted to a 12 weeks program of neuromuscular electrical stimulation (NMES group)
* patients without any program (control group) All patients will also receive a study participation guide that will include an information leaflet outlining tips for active living and walking.

After eligibility criteria will be assessed, patient will be included and randomized (visit 1). A second visit will be performed after 12 weeks (visit 2).

In parallel, 2 ancillary studies will be performed :

* Among Rennes' arteriopatic patients, endothelial function will be assessed using measures from 40 patients. Assessment will be done between 1 and 14 days after visit 1 (visit 1')
* The second ancillary study concerns 40 volunteers with no cardiac or vascular pathology, only in the coordinating center Rennes. The same measures will be performed for these volunteers and for arteriopatic patients.

Eligibility criteria: Inclusion Criteria:

Arteriopatic patients :

* Age \> 40 years old.
* Subjects with Lower Extremity Peripheral Artery disease (LEPAD). LEPAD is defined by the presence of at least one of the following criteria:

  * History of revascularization in the lower limbs due to LEPAD; OR
  * Ankle brachial index (ABI) of ≤ 0.90; OR
  * ABI or ankle systolic blood pressure decrease during recovery from treadmill walking test \> 20 % or \> 30 mmHg, respectively; OR
  * Toe-brachial index ≤0.70 if ABI cannot be measured and if incompressible arteries are suspected.
* Complain of exertional calf pain (fatigue, discomfort or cramping) that can begin or not at rest, causes the participant to stop walking and relieves or lessens within 10 minutes of rest (assessed using the San Diego questionnaire AND confirmed during treadmill testing);
* Pain (fatigue, discomfort or cramping) is mainly located at the calves' level.
* Maximal walking distance on treadmill \< 300 m (treadmill protocol 3.2 km/h, 10% grade);
* Subject receiving from at least one month the recommend medical therapy for LEPAD management (antiplatelet therapy and statin medication).
* Obtained informed consent.

Healthy volunteers

* Age \> 50 years old;
* Absence of pain reported in the lower limbs during walking as supported by a negative score in the San Diego Questionnaire;
* Absence of any functional limitation during the treadmill walking test: 15 min of walking at 3.2 km/h and 10% slope;
* ABI ≥1.00 and ≤1.40.
* Obtained informed consent.

Exclusion Criteria:

Arteriopatic patients :

* Patients with a pacemaker or defibrillator;
* Patients with acute or critical limb ischemia;
* Ambulation limited by exertional symptoms other than intermittent claudication (e.g., dyspnea or angina pectoris);
* Ambulation limited by exertional symptoms indicative of intermittent claudication but affecting muscles in the lower extremities other than the calves;
* Contraindication to exercise testing according to the American Heart Association and the American College of Sports Medicine;
* Major cardiovascular event (myocardial infarction or stroke) or major surgery within the previous three months before inclusion;
* Female patients who are pregnant, planning to become pregnant, or lactating;
* Known presence of an aneurysm of the abdominal aorta \> 4cm or an aneurysm of the iliac artery \>1.5cm;
* Patient subject to legal protection (guardianship or tutelage measure) and persons deprived from their liberty (according to French law);
* Simultaneous participation to another ongoing clinical research protocol;
* Unwilling or unable to engage in the completion of a 12 week programme;
* Any planned event(s) that could interfere with the completion of the protocol: e.g., extended holidays preventing the completion of the intervention or planned hospitalization for a prolonged period of time.
* Body mass \> 160 kg (may exceed treadmill limit).
* Inability to understand and sign informed consent forms due to cognitive or language barriers
* LEPAD due to other causes than atherosclerosis.

Healthy volunteers :

* Contraindication to walking;
* ABI \<1.00 or \>1.40;
* Inability to obtain a measure of ABI due to uncompressible arteries;
* Limitation(s) and/or symptoms during the treadmill walking test;
* Treadmill walking test uncompleted.
* Presence of hypertension, heart failure, angina pectoris, diabetes, chronic obstructive pulmonary disease, supported by the presence of a medical treatment and the medical history.
* Presence of conditions likely to cause a functional limitation in walking and/or significant modification of physiological responses to the exercise: current or former smoker from less than 6 months, cancer (ongoing), Parkinson's disease, renal failure (ongoing), supported by the presence of a medical treatment and the medical history.
* History of cardiovascular disease (heart failure, stroke, myocardial infarction) reported by the patient.
* Female volunteers who are pregnant, planning to become pregnant, or lactating;
* Volunteers subject to legal protection (guardianship or tutelage measure) and persons deprived from their liberty (according to French law).
* Simultaneous participation to another ongoing clinical research protocol.

Secondary exclusion criteria for patients :

1. Patients requiring a pacemaker or defibrillator within the first three months.
2. For the primary endpoint, patients who underwent revascularisation (surgical or endovascular) in the first three months.

   revascularisation (surgical or endovascular) in the first three months.
3. 3. Any health events during the first three months that no longer allow the patient to follow the protocol.
4. Burning during the electrostimulation sessions;
5. Skin allergy due to the placement of the electro-stimulation electrodes

Primary outcomes:
measure: Change in treadmill walking distance to maximal leg pain (absolute walking distance)
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in treadmill walking distance to onset of leg pain
timeFrame: 12 weeks
measure: Change in 6-minute total walk distance
timeFrame: 12 weeks
measure: Change in maximal walking distance and medium walking speed under natural outdoor conditions
timeFrame: 12 weeks
measure: Change in the Walking Impairment Questionnaire score
timeFrame: 12 weeks
measure: Change in the Short Form (36) Health Survey (SF36) score
timeFrame: 12 weeks
measure: Change in the Peripheral Artery Questionnaire (PAQ) score
timeFrame: 12 weeks
measure: Change in in actigraphy measures
timeFrame: 12 weeks
measure: Change in ankle brachial index
timeFrame: 12 weeks
measure: Change in TcPO2 DROP during treadmill walking test
timeFrame: 12 weeks
measure: Number of patients submitted to a revascularization procedure
timeFrame: 12 weeks
measure: Change in results of Contrast imaging with laser granularity
timeFrame: 12 weeks
measure: Percentage of physiological response achieved by patients
timeFrame: 12 weeks
measure: Change in maximum walking distance according to the location of the arterial obstruction
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHU Brest
city: Caen
country: France
facility: CHU Caen
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: Hôpital de Rangueil
Study officials:
affiliation: Rennes University Hospital
name: Guillaume Mahe, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jehannin P, Craughwell M, Omarjee L, Donnelly A, Jaquinandi V, Mahe G, Le Faucheur A. A systematic review of lower extremity electrical stimulation for treatment of walking impairment in peripheral artery disease. Vasc Med. 2020 Aug;25(4):354-363. doi: 10.1177/1358863X20902272. Epub 2020 Apr 17.