Does Neuromuscular Electrical Stimulation Improve the Absolute Walking Distance in Patients With Intermittent Claudication Compared to Best Available Treatment?

Study Overview
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Brief Summary
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Intermittent claudication (IC) is caused by a blockage in the artery of the leg, causing muscle pain. Although some evidence of the efficacy of neuromuscular electrical stimulation (NMES) in the management of patients with IC exists, further high quality research is required. This proposed study is vital to identify the contribution of clinical change using NMES, compared to the current gold standard recommended practice of supervised exercise therapy (SET) and, actual standard of care offered in the majority of the UK and Ireland, including best medical therapy (BMT). The device is expected to increase the walking distance in patients with intermittent claudication (IC), and therefore have a benefit on the same when provided in addition to supervised exercise programmes. It is also expected to cause a reduction in pain symptoms and reduced likelihood of major intervention in late stage peripheral arterial disease (PAD). The principal research objective is to assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device as an adjunct to the local standard care that is available at the study randomisation sites, in order to improve walking distance in patients with intermittent claudication (IC).

Official Title
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A Multicenter Randomised Controlled Study: Does Neuromuscular Electrical Stimulation Improve the Absolute Walking Distance in Patients With Intermittent Claudication (NESIC) Compared to Best Available Treatment?

Conditions
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Intermittent Claudication, Peripheral Vascular Diseases

Intervention / Treatment
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* Device: NMES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capacity to provide informed consent Aged 18 or above Positive Edinburgh Claudication Questionnaire ABPI <0.9 OR positive stress test (fall in ankle pressure >30mmHg, 40 secs post 1 min treadmill at 10% gradient, 4 km/h) Exclusion Criteria: Severe IC requiring invasive intervention as determined by the treating clinician Critical limb Ischaemia as defined by the European Consensus Document Co-morbid disease prohibiting walking on a treadmill or taking part in supervised exercise therapy. Popliteal entrapment syndrome Commenced vascular symptom specific medication in previous 6 months e.g. naftidrofuryl oxalate, cilostazol Pregnancy Any implanted electronic, cardiac or defibrillator device Acute deep vein thrombosis Broken or bleeding skin including leg ulceration Peripheral neuropathy Recent lower limb injury or lower back pain

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>There will be no change to the local site standard of care for patients with IC attributed to participation in this trial. Those sites with Supervised Exercise Therapy (SET) will continue to provide this intervention as per their normal standard of care and locally agreed protocol. | |
| Experimental: Device<br>Local therapy + Neuromuscular Electrical Stimulation (NMES) | Device: NMES<br>* NMES device to be used for up to 3 hours daily in 30 minute sessions for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute walking distance (AWD) | measured by treadmill testing | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial claudication distance (ICD) | measured by treadmill testing | 3 months | 
| Quality of life - Intermittent Claudication Questionnaire (ICQ) | Patient questionnaire. Used to assess change in disease-specific QoL. | Baseline, 3 month, 6 month and 12 months | 
| Quality of life - EuroQoL 5D (EQ5D) | Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement. | Baseline, 3 month, 6 month and 12 months | 
| Quality of life Short Form 36 (SF-36) | Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement. | Baseline, 3 month, 6 month and 12 months | 
| Haemodynamic assessment - Duplex ultrasonography | Using an arterial ultrasound probe and pre-set volume flow algorithms on a duplex ultrasound machine, flow within the common femoral artery (CFA), of the most affected limb, will be measured, approximately 5cm below the mid-inguinal point at the groin. Measures include volume flow (VF, cc/min) and time-averaged mean volume (TAMV, cm/s) to assess whether using the device increases these measurements. | Baseline, 3 month, 6 month and 12 months | 
| Haemodynamic assessment - Laser Doppler Flowmetry (LDF) | The single fibre laser optical probe of the LDF machine will be positioned on the dorsal aspect of the foot using single use adhesive pads. Flux, as a measure of superficial skin blood flow will be measured to assess whether using the device increases this measurement. | Baseline, 3 month, 6 month and 12 months | 
| Haemodynamic assessment - Laser Doppler Flowmetry (LDF) | The single fibre laser optical probe of the LDF machine will be positioned on the dorsal aspect of the foot using single use adhesive pads. Skin surface temperature will be measured to assess whether using the device increases this measurement. | Baseline, 3 month, 6 month and 12 months | 
| Haemodynamic assessment - Ankle Brachial Pressure Index (ABPI) | The brachial blood pressure from the right arm using a manual blood pressure monitor cuff and Doppler will be recorded after 5 minutes of resting supine on a couch. The systolic blood pressure of the anterior tibial artery and posterior tibial artery at the ankle will also be recorded using the cuff and Dopplermethod. The ratio of the systolic brachial and ankle pressures will form the ABPI measurement. | Baseline, 3 month, 6 month and 12 months | 
| Health economic assessment | The economic analyses will compare local therapy (SET or EA only) versus the intervention (local therapy + Neuromuscular Electrical Stimulation, NMES) in patients with Intermittent Claudication. The analyses will be based on a (i) patient level in-trial cost-effectiveness analysis, (ii) a decision model and (iii) budget impact assessment. The in-trial analysis will calculate quality-adjusted life years (QALYs) over the one year time horizon of the trial. | Baseline, 3 month, 6 month and 12 months | 
| Compliance with interventions | Comparison of compliance with NMES device compared to SET classes. NMES compliance data collected from the data logger fitted to device and patient diary will be combined to report overall compliance. | 3 months | 
| Device experience questionnaire | To report ease of device use and suggest any developments. | 3 months |