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

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?

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).

Study Overview

• Status: Completed
• Conditions: Peripheral Vascular Diseases; Intermittent Claudication
• Intervention / Treatment: Device: NMES

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom
    • The Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust
  • Bristol, United Kingdom, BS10 5NB
    • North Bristol NHS Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Dorchester, United Kingdom
    • Dorset County Hospital Nhs Foundation Trust
  • Hull, United Kingdom, HU3 2JZ
    • Hull and East Yorkshire Hospitals NHS Foundation Trust
  • London, United Kingdom
    • St George's University Hospitals NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust
  • Newcastle, United Kingdom, NE7 7DN
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom, NG7 2RD
    • Nottingham University Hospitals NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust
  • Taunton, United Kingdom, TA1 5DA
    • Taunton and Somerset NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; 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; Local therapy + Neuromuscular Electrical Stimulation (NMES)	Device: NMES; NMES device to be used for up to 3 hours daily in 30 minute sessions for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	Measured by treadmill testing. Absolute walking distance in meters at baseline and 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the Initial Claudication Distance (ICD) at 3 Months Between the Two Treatment Groups	Measured by treadmill testing. ICD in meters at baseline and 3 months	3 months
Quality of Life - Intermittent Claudication Questionnaire (ICQ)	Patient questionnaire. Used to assess change in disease-specific QoL.	Baseline, 3 months, 6 months, 12 months
Quality of Life - EuroQoL 5D (EQ5D) Health Scale	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) Physical Component Summary	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 - Difference in Volume Flow Between Baseline and 3 Months	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) to assess whether using the device increases this measurement.	3 months
Haemodynamic Assessment - Laser Doppler Flowmetry (LDF) - Difference in Blood Flux Between Baseline and 12 Months	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 - Difference in Ankle Brachial Pressure Index (ABPI) - Left - Between Baseline and 12 Months	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 (supervised exercise therapy (SET) or exercise advice (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 - Exercise Advice (EA)	Comparison of compliance with exercise advice as per local standard of care.	3 months
Device Experience Questionnaire - Ease of Use	To report ease of device use and suggest any developments.	3 months
Quality of Life - EuroQoL 5D (EQ5D) Health Index	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.	Baseline, 3 months, 6 months, 12 months
Quality of Life Short Form 36 (SF-36) Mental Component Summary	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.	Baseline, 3 months, 6 months, 12 months
Haemodynamic Assessment - Duplex Ultrasonography - Difference in Time Average Mean Velocity Between Baseline and 3 Months	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 time-averaged mean volume (TAMV, cm/s) to assess whether using the device increases this measurement.	3 months
Haemodynamic Assessment - Difference in Ankle Brachial Pressure Index (ABPI) - Right - Between Baseline and 12 Months	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 months, 6 months and 12 months
Compliance With Interventions - Supervised Exercise Therapy (SET)	Comparison of compliance with SET classes.	3 months
Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)	Compliance with NMES device. 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 - Reduces Leg Pain	To report ease of device use and suggest any developments.	3 months
Device Experience Questionnaire - Increased Walk Distance	To report ease of device use and suggest any developments.	3 months
Device Experience Questionnaire - Used as Instructed	To report ease of device use and suggest any developments.	3 months
Device Experience Questionnaire - Could Have Used More	To report ease of device use and suggest any developments.	3 months
Device Experience Questionnaire - Used After Treatment	To report ease of device use and suggest any developments.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sub-group Analysis 1 - Difference in Absolute Walking Difference Between Baseline and 3 Months SET Sites vs Non-SET Sites	Subgroup analysis 1: Right censored Tobit regression model for AWD at 3 months to assess the effects SET sites vs non-SET sites (NMES+SET+BMT & SET+BMT vs NMES+BMT & BMT).	3 months
Sub-group Analysis 2 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+SET+BMT vs SET+BMT)	Subgroup analysis 2: Right censored Tobit Regression model for AWD at 3 months to assess the effects of NMES in the SET sites (NMES+SET+BMT vs SET+BMT).	3 months
Sub-group Analysis 3 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+BMT vs BMT)	Subgroup analysis 3: Right censored Tobit regression model for the AWD at 3 months to assess the effects of NMES in the non-SET sites (NMES+BMT vs BMT).	3 months
Sub-group Analysis 4 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+BMT vs. SET+BMT)	Subgroup analysis 4: Right censored Tobit regression model for AWD at 3 months to assess the effects of (NMES+BMT) has a similar effect as (SET+BMT).	3 months
Sub-group Analysis 5 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+SET+BMT vs. NMES+BMT)	Subgroup analysis 5: Determine if (NMES+SET+BMT) is more effective than (NMES+BMT).	3 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Professor Davies, Chief Investigator

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: February 19, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication
• Other Study ID Numbers: 17HH4216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No