Randomized clinical trial

Effect of footplate neuromuscular electrical stimulation on

functional and quality-of-life parameters in patients with
peripheral artery disease: pilot, and subsequent randomized
clinical trial
A. Babber1 , R. Ravikumar1 , S. Onida1,2 , T. R. A. Lane1,2 and A. H. Davies1,2
1
Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, and 2 Department of Vascular Surgery, Imperial College
Healthcare NHS Trust, London, UK

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Correspondence to: Professor A. H. Davies, Department of Vascular Surgery, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Floor 4
East, Room 04, Fulham Palace Road, London W6 8RF, UK (e-mail: a.h.davies@imperial.ac.uk)

Background: Supervised exercise programmes for intermittent claudication have poor access and lim-
ited compliance. Neuromuscular electrical stimulation (NMES) may be an effective alternative. A
proof-of-concept study and RCT were conducted.
Methods: In study 1, eligible patients underwent baseline assessment; treadmill testing for initial
(ICD) and maximum (MCD) claudication distance; EuroQoL Five Dimensions five-level instrument
(EQ-5D-5L™) and Intermittent Claudication Questionnaire (ICQ) assessment; and measurement of
ultrasound haemodynamics of the superficial femoral artery. After familiarization with the NMES device,
participants underwent a 30-min session of stimulation with concomitant recording of haemodynamic
measures at 15 min, and after device cessation. Measurements were repeated after 6 weeks of daily use
of NMES. In study 2, consecutive patients underwent baseline assessment before online randomization
to a supervised exercise programme only, or adjunctive NMES treatment for 6 weeks, followed by repeat
measurements.
Results: Study 1 (20 patients) showed a significant improvement in MCD (46 per cent; P < 0⋅001) and
ICD (71 per cent; P < 0⋅001). The RCT (42 patients) showed a significant adjunctive benefit of NMES in
ICD (46 per cent; P = 0⋅014). Improvements were seen in the ICQ (9 points; P = 0⋅009) and EQ-5D-5L™
(P = 0⋅007) in study 1, and there was a significant adjunctive benefit of NMES on the ICQ score in patients
who did supervised exercise (11⋅2 points; P = 0⋅031). Blood volume flow and time-adjusted mean velocity
increased significantly with the device on (P < 0⋅050). Overall, NMES compliance exceeded 95 per cent.
Conclusion: Footplate NMES significantly improved walking distance in patients with intermittent
claudication when used independently and also as an adjunct to supervised exercise. Registration number:
trial 1, NCT02436200; trial 2, NCT02429310 (http://www.clinicaltrials.gov).

Paper accepted 18 September 2019

Published online 7 January 2020 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.11398

Introduction the UK population are estimated to be suffering from IC4 ,

Peripheral artery disease (PAD) has a significant global
health and economic impact, with a worldwide estimate of
200 million people affected1 . In the USA, annual healthcare
expenditure on management is US $4⋅37 billion (€3⋅90
billion; exchange rate 2 November 2019)2 . The average
annual prevalence in high-income countries is 5 per cent
for those aged 45–49 years, rising to over 18 per cent in
85–89-year-olds3 .
Intermittent claudication (IC) is the most common clin-
ical manifestation of PAD; between 5 and 10 per cent of
a functionally debilitating symptom with significant detri-
ment to quality of life (QoL).
International guidelines5 – 7 advise initial management
with lifestyle and risk factor modification, and best med-
ical therapy to prevent progression of PAD. Strong evi-
dence exists for the benefit of exercise therapy, particularly
in the form of a supervised exercise programme (SEP), in
improving walking distances8 – 10 . The National Institute
for Health and Care Excellence (NICE) guidance6 recom-
mends 2 h of supervised exercise per week for 3 months

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Published by John Wiley & Sons Ltd
356
as first-line management of PAD. However, this resource
is underutilized and frequently inaccessible in the UK
and worldwide, largely owing to a lack of funding and
patient compliance11 – 13 . Alternative management strate-
gies that are clinically effective, non-invasive and accessible
are therefore needed.
Neuromuscular electrical stimulation (NMES) is an
emerging technology that may fulfil this role. NMES uses
electrical energy applied externally, sufficient to stimulate
nerve conduction, resulting in active muscle contrac-
tion. In the leg, this contraction actions the calf muscle
pump, potentially aiding lower limb circulation. Current
literature suggests that using NMES within sufficient
parameters can improve lower limb arterial and venous
haemodynamics in healthy individuals14 . There remains a
paucity of good evidence-based literature concerning the
use of NMES in PAD and, more so, comparing any effect
with a SEP.
Therefore, the aim of this study was twofold. First, a
pilot proof-of-concept experiment was done to assess func-
tional or QoL changes exclusively using an NMES medical
device; second, a powered RCT was undertaken to ascer-
tain any adjunctive benefit of using the NMES device with
a SEP compared with a SEP in isolation for IC.
Methods
Patient selection
IC was diagnosed using the Edinburgh Claudication Ques-
tionnaire, which has a sensitivity of 91⋅3 per cent and a
specificity of 99⋅3 per cent15 .
According to Inter-Society Consensus for the Manage-
ment of Peripheral Arterial Disease (TASC II) guidance5 ,
people with an ankle : brachial pressure index (ABPI) mea-
surement of less than 0⋅90 have PAD. This has a sensitiv-
ity of 97 per cent and specificity of 100 per cent in this
context16 , and was used as baseline marker for identifying
patients with IC.
Outcomes
Treadmill walking distance
Treadmill tests have been recommended and used exten-
sively in measuring objective walking capacity, and changes
following intervention, in patients with PAD5,17 . A con-
stant load treadmill test was used to measure both the pri-
mary outcome, maximum claudication distance (MCD),
and the initial claudication distance (ICD). The former
is defined as the walking distance at which the patient is
forced to stop exercising because of IC, and the latter is
the distance walked before the onset of symptoms. The
© 2020 BJS Society Ltd
Published by John Wiley & Sons Ltd
A. Babber, R. Ravikumar, S. Onida, T. R. A. Lane and A. H. Davies
treadmill test was carried out at 3⋅5 km/h with a 10 per cent
gradient. This test was used because of its reproducibility,
acceptable reliability18 and similarity to the testing proto-
col used during a SEP.
Quality-of-life questionnaires
QoL assessment was done using the validated generic
EuroQoL Five Dimensions five-level instrument
(EQ-5D-5L™; EuroQol Group, Rotterdam, the Nether-
lands) and the disease-specific Intermittent Claudication
Questionnaire (ICQ). The ICQ has a reliability index of
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0⋅94 and correlates well with the EQ-5D-5L™ (r = 0⋅57)19 .
Ultrasound haemodynamic assessment
A Philips iU22 ultrasound machine (Philips Electronics
UK, Guildford, UK) with the vascular measurement pro-
tocol and an L12-5 transducer probe was used to assess
the superficial femoral artery diameter (cm), time-adjusted
mean velocity (TAMV, cm/s) and blood volume flow
(ml/min) in the leg in the seated position. Blood flow
comprises the volume of blood crossing a single point of
the superficial femoral artery, whereas TAMV is the rate
of change of blood flow at this point. An area 10–15 cm
below the mid-inguinal point of the more symptomatic leg
with the best view of the longitudinal cross-section of the
superficial femoral artery was marked with a pen and used
for all ultrasound haemodynamic measures. A transducer
angle correction of 60∘ was adopted for optimal blood flow
assessment in the femoral artery. As ultrasound haemody-
namic measures are known to be user-dependent, to main-
tain reliability, the measurements were carried out by the
same author in all patients. A reliability assessment showed
all intrarater indices to fall within the acceptable range of
95 per cent confidence intervals.
Tissue oxygenation
Laser wavelength technology in the form of a laser Doppler
flowmeter (LDF) was used to assess the skin temperature
and microcirculation (measured in arbitrary units, AU) as
measures of blood flux. A dual-channel moorVMS-LDF
device (Moor Instruments, Axminster, UK) was used with
two optical probes, one each attached with custom adhe-
sive tape to the back of the hand and the dorsum of the
foot. Patients had rested for at least 15 min before use of
the LDF.
Neuromuscular electrical stimulation medical device
The Revitive™ IX NMES device (Actegy, Bracknell, UK)
is a class II, CE-certified medical device that provides elec-
trical stimulation via footplate electrodes on a rocking base;
it maintains full contact with the soles of the feet while
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Footplate neuromuscular electrical stimulation in peripheral artery disease
calf muscle contraction occurs. On activation, the device
cycles twice through 15 preprogrammed stimulation pat-
terns, each lasting approximately 1 min, for a total session
duration of 30 min. The stimulation parameters for the
device include a frequency of 1–50 Hz and a maximum out-
put current of 15 mA applied in quasi-symmetrical biphasic
rectangular or bipolar waveforms. The pulse duration is
370 or 940 μs with 11–256 pulses per burst, 0⋅1–0⋅3 bursts
per s, and a burst duration of 1⋅9–8⋅4 s depending on the
stimulation pattern. Direct skin contact with the soles of
both feet is required.
The intensity of stimulation is user-defined between 0
and 99, and controlled from the device display directly or
by remote control. The most appropriate intensity level
is established by ascertaining the sensory threshold (min-
imum intensity level of sensory stimulation) and then the
motor threshold (minimum intensity for visible calf muscle
contraction). The ideal therapeutic intensity is then calcu-
lated as being twice the motor threshold level, but adjusted
according to user comfort. The device display shows a
countdown of session duration.
Study 1
The aim of this proof-of-concept study was to ascertain
whether a change in function and QoL would occur when
the NMES medical device was used in patients with IC.
This was a prospective, observational cohort study that
included all non-diabetic patients with IC of the legs with
no tissue loss. Patients were excluded if the ABPI was
0⋅90 or higher, or they were unable to comply with the
study protocol, had any implanted electrical or defibrillator
device, or recent leg injury.
Ethical approval for this study was obtained from the
National Research Ethics Service (NRES) Committee
East of England – Cambridge Central (REC refer-
ence 14/EE/0086). Approval was also gained from the
Medicines and Healthcare products Regulatory Authority
(MHRA). The trial was registered at ClinicalTrials.gov
(registration number NCT02436200).
Sample size
The target study sample size was 20 patients, which was
considered a plausible, realistic number to achieve the
study aims. Owing to limited previous research in this area,
a formal sample size calculation was not possible.
Study protocol
Patients meeting the inclusion criteria were screened
prospectively, provided study information, consented and
recruited from the vascular outpatient clinic at Charing
Cross Hospital, Imperial College Healthcare National
© 2020 BJS Society Ltd
Published by John Wiley & Sons Ltd
357
Health Service (NHS) Trust, London, UK. A baseline
appointment was arranged during which demographic and
anthropometric data were collected, including a medical
history, peripheral artery examination and baseline ABPI
measurement. A treadmill test was carried out to measure
the ICD and MCD. Patients were then rested for 15 min
during which they completed the generic EQ-5D-5L™
and disease-specific ICQ QoL questionnaires.
After the rest, a brief induction was provided to familiar-
ize the patients with the NMES device and establish the
appropriate therapeutic stimulation threshold. Following
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the induction, patients had the opportunity to ask ques-
tions and the NMES intervention session started approxi-
mately 15 min later after setting up the recording devices.
Before starting this session, baseline ultrasound haemo-
dynamic parameters were recorded from the superficial
femoral artery after marking the chosen recording area
with a marker pen. Optical probes from the LDF machine
were attached to the dorsum of the hand and ipsilateral
foot, recording the skin temperature and blood flux at each
site continuously. Patients then set the NMES intensity
level at the predefined therapeutic motor threshold level
and remained seated during the 30-min session. Further
ultrasound haemodynamic data were collected 15 min into
device use, and then within 1 min after cessation of NMES.
Each patient was supplied with a device to use at home
for 30 min daily for a total of 6 weeks. A compliance diary
was provided to note the frequency of device use and inten-
sity parameters used. A follow-up appointment was made
for 6 weeks, at which the treadmill test, QoL question-
naires, haemodynamic measures and LDF assessment were
repeated. The study protocol is shown in Fig. 1a.
Outcomes
The primary outcome measure for study 1 was MCD.
Secondary outcome measures included: ICD; QoL scores
from the EQ-5D-5L™ and ICQ questionnaires; ultra-
sound haemodynamic measures, including superficial
femoral artery diameter, TAMV and blood flow; and tissue
oxygenation measured using the LDF.
Study 2
The aim was to assess the adjunctive functional and QoL
benefit of NMES over SEP in the management of IC.
This RCT included all patients with IC who were able
to complete a SEP. Patients were excluded if the ABPI
was 0⋅90 or over, they were unable to comply with the
study protocol, had any implanted electrical or defibrillator
device, or recent leg injury.
Ethical approval for this study was obtained from the
Cambridge Central NRES (REC reference 14/EE/0193).
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358
Fig. 1 Study protocols
a Study 1
Patient screening
Outpatient clinic
Inclusion/exclusion criteria
Patient information sheet provided
Baseline appointment
Consent
Full history and examination
Baseline ABPI, treadmill test
Quality of life (ICQ, EQ-5D-5LTM)
NMES device orientation
NMES device use
Ultrasound haemodynamics
Laser Doppler flowmetry
Home intervention Group A
NMES SEP only
Compliance diary
Follow-up week 6
Treadmill test
Quality of life (ICQ, EQ-5D-5LTM)
NMES device use
Ultrasound haemodynamics
Laser Doppler flowmetry
a Study 1 and b study 2. ABPI, ankle : brachial pressure index; ICQ, Intermittent Claudication Questionnaire; EQ-5D-5L™, EuroQoL Five Dimensions
five-level instrument; NMES, neuromuscular electrical stimulation; SEP, supervised exercise programme.
The MHRA also approved the study. The trial was
registered at ClinicalTrials.gov (registration number
NCT02429310).
Sample size
The total sample size for study 2 was calculated to be 45
patients, based on data from a previous study20 considering
the change in primary outcome with a SEP in patients with
IC. This represented a 60-m change in walking distance,
assuming a standard deviation of 120 m, with 90 per cent
power and a 5 per cent significance level. The sample
size for this study was calculated using an online software
tool from the Massachusetts General Hospital Biostatistics
Center (http://hedwig.mgh.harvard.edu/biostatistics/).
Supervised exercise programme
All patients in this RCT attended a SEP at Charing Cross
Hospital. All eligible patients with IC normally had a SEP
booked in within 2–3 weeks of referral from the vascular
outpatient clinic, and attended the baseline clinical trial
appointment within a week of the SEP date.
© 2020 BJS Society Ltd
Published by John Wiley & Sons Ltd
A. Babber, R. Ravikumar, S. Onida, T. R. A. Lane and A. H. Davies
b Study 2
Patient screening
Outpatient clinic
Inclusion/exclusion criteria
Patient information sheet provided
Baseline appointment
Consent
Full history and examination
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Baseline ABPI, treadmill test
Quality of life (ICQ, EQ-5D-5LTM)
NMES device orientation
Randomization
NMES device use (group B only)
Ultrasound haemodynamics
Laser Doppler flowmetry
Group B
NMES and SEP for 6 weeks
Follow-up week 6
Treadmill test
Quality of life (ICQ, EQ-5D-5LTM)
NMES device use (group B only)
Ultrasound haemodynamics
Laser Doppler flowmetry
The SEP took place in an open gym facility in the physio-
therapy department, led by a fully trained physiotherapist
and physiotherapy assistant. The programme consisted of
a 1-h session weekly for a total of 6 months, during which
a circuit of lower limb-specific exercises were carried out
including walking, steps, treadmill, exercise bike, obstacle
walk and passive stretching. The class size limit was approx-
imately eight participants to ensure sufficient access to all
gym equipment and exercises.
Study protocol
This study followed the same protocol as the pilot study,
except that eligible patients had to be able to complete a
concurrent SEP during the 6-week study (Fig. 1b). Patients
were randomized with an allocation ratio of 1 : 1 to either
SEP only (group A) or SEP and NMES (group B). Ran-
domization was undertaken using an online randomization
protocol (https://www.sealedenvelope.com) during the
patient appointment, with no previous knowledge of the
online sequence and full concealment.
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Footplate neuromuscular electrical stimulation in peripheral artery disease
Outcomes
The primary and secondary outcome measures were the
same as those in study 1. Compliance with the NEMS
device was measured using a diary completed by each
patient.
Statistical analysis
All raw and scored data were transcribed on to a database in
Excel® (Microsoft, Redmond, Washington, USA), where
basic statistical analyses were done. Further statistical
analysis was completed using GraphPad Prism® version
5.0–7.0 (GraphPad Software, La Jolla, California, USA).
Where appropriate, following visual assessment, confir-
matory normality testing of data was undertaken using the
D’Agostino and Pearson formula and the Shapiro–Wilk
test. Paired t test was used for analysis of paired nor-
mal data and the Wilcoxon matched-pairs signed-rank
test if the paired data had a non-normal distribution.
Unpaired, non-normal data underwent Mann–Whitney
analysis. If normality tests revealed a mixture of normal and
non-normal data sets, further statistical analysis was car-
ried out by non-parametric methods. Repeated-measures
data collected over three time points of each NMES ses-
sion (ultrasound haemodynamic data) were subjected to
one-way ANOVA, with Bonferroni correction when multi-
ple t tests were used to compare data sets. The significance
level was set at P < 0⋅050.
Results
Study 1
Twenty consecutive patients, with a mean age of 70 years,
completed the study protocol successfully (Fig. S1, sup-
porting information); there were 16 men. The majority (16)
were ex-smokers, and treated with best medical therapy
for control of hypertension (16) and hypercholesterolaemia
(18). Eleven patients had superficial femoral artery disease.
Mean cohort ABPI measurements were 0⋅71 on the right
and 0⋅69 on the left (Table S1, supporting information).
Walking distance
After 6 weeks of NMES, there was a significant increase in
MCD of 40⋅7 m (46 per cent; P < 0⋅001) (Fig. 2a). During
the same interval, the median ICD increased significantly
by 26⋅6 m (71 per cent; P < 0⋅001) (Fig. 2b).
Quality of life
The disease-specific ICQ scores showed a significant
improvement, from a mean of 44⋅0 to 35⋅2, a 20 per cent
reduction over the 6-week NMES (P = 0⋅009) (Fig. S2a,
supporting information). Generic EQ-5D-5L™ scores
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Published by John Wiley & Sons Ltd
359
Fig. 2 Walking distances at week 0 and week 6 following use of
neuromuscular electrical stimulation in study 1
a Initial claudication distance
*
250
200
Distance (m)
150
100
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50
0
Week 0 Week 6
b Maximum claudication distance
*
800
600
Distance (m)
400
200
0
Week 0 Week 6
a Initial claudication distance and b maximum claudication distance. Indi-
vidual and median (i.q.r.) values are shown. *P < 0⋅001 (paired t test).
improved significantly from a median of 0⋅63 to 0⋅70
in the same interval (P = 0⋅007) (Fig. S2b, supporting
information).
Ultrasound measurements
The superficial femoral artery diameter did not differ sig-
nificantly over the three time points measured at week 0
(F = 2⋅63, P = 0⋅160) or at week 6 (F = 0⋅286, P = 0⋅642)
after NMES use. No significant difference was found
between measurements taken at each time point at week
0 versus week 6 (Table S2, supporting information).
Blood volume flow increased significantly after 15 min of
device use compared with baseline at week 0 (P = 0⋅013),
but this was not replicated at week 6 (P = 0⋅151). There was
a significant decrease in blood volume flow from 15 min
of device use compared with measurements taken 1 min
after device cessation both at week 0 (P = 0⋅001) and week
6 (P = 0⋅007). There was no difference between measure-
ments taken at the same time point at week 0 and week 6
(Table S2, supporting information).
TAMV showed a significant increase between baseline
and after 15 min of device use at week 0 (P = 0⋅011) and
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360 A. Babber, R. Ravikumar, S. Onida, T. R. A. Lane and A. H. Davies

Fig. 3 Walking distances at week 0 and week 6 in study 2

a ICD and MCD in group A b ICD and MCD in group B

†
500 800 †

400 †
600

Distance (m)
Distance (m)

300 †
400
200
200

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100

0 0
Week 0 Week 6 Week 0 Week 6 Week 0 Week 6 Week 0 Week 6
ICD MCD ICD MCD

c Change in ICD over 6 weeks in groups A and B

*
200

150
ICD (m)

100

50

–50
Group A Group B

Initial claudication distance (ICD) and maximum claudication distance (MCD) at 0 and 6 weeks in a group A (supervised exercise programme, SEP) and
b group B (SEP and neuromuscular electrical stimulation), and c change in ICD over 6 weeks in groups A and B. Individual and median (i.q.r.) values are
shown. *P < 0⋅050, †P < 0⋅010 (a,b Wilcoxon test, c Mann–Whitney U test).

week 6 (P = 0⋅021). There was a significant reduction in
TAMV on completion of the NMES session compared
with after 15 min of device use at week 0 (P = 0⋅004) and
week 6 (P < 0⋅001). Comparison of measurements taken
at the same time point at week 0 and week 6 revealed no
difference (Table S2, supporting information).
Laser Doppler flowmetry
There was no significant difference in temperature or
blood flux either relating to device status (baseline, on or
cessation) or over the 6-week intervention.
Compliance
Analysis of compliance diaries, completed by all patients,
showed a mean adherence rate of 97 (range 81–100) per
cent over the 6-week intervention. Patients reported good
ability to tolerate the device and ease of incorporation into
daily routine.
Study 2
Seventy-five patients from the vascular outpatient clinic
were screened, of whom 42 eligible patients were recruited
to start the trial. Of these, 22 were randomized to SEP only
(group A) and 20 to SEP with adjunctive NMES (group
B). One patient from each group was excluded during the
baseline appointment owing to inability to carry out the
treadmill test. Of the patients initially recruited, baseline
measurements were taken for 21 in group A and 19 in group
B. One patient from each group did not attend the 6-week
follow-up, and there was a further exclusion from group B
as one patient was unable to continue the study following
a motorcycle accident. Twenty patients from group A and
17 from group B completed the study protocol (Fig. S3,
supporting information).
There was no significant difference in demographic vari-
ables between the groups; there were 15 men in group A
and 14 in group B, and the mean age was 68 and 66 years
respectively (Table S3, supporting information).
Walking distances
The MCD and ICD both increased significantly over
6 weeks in group A (64 and 41 per cent respectively)
(Fig. 3a) and group B (40 and 41 per cent) (Fig. 3b). At week
6, the ICD was 46 per cent greater in group B than group A

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Footplate neuromuscular electrical stimulation in peripheral artery disease
(P = 0⋅014) but there was no significant difference between
groups in MCD (14 per cent; P = 0⋅283). The change in
ICD in group B over 6 weeks was significantly greater than
that in group A (40⋅4 versus 7⋅5 m respectively; P = 0⋅012)
(Fig. 3c).
Quality of life
Group A showed no difference from baseline to 6 weeks in
disease-specific ICQ scores (9 per cent improvement, 4⋅2
points; P = 0⋅413). Group B showed a significant improve-
ment in ICQ scores of 23 per cent (11⋅2 points; P = 0⋅031).
There was no significant difference in absolute scores
between groups at week 6 (group A 43⋅7 versus group B
37⋅1; P = 0⋅174) (Table 1). However, comparison of the
score change between groups showed a significant differ-
ence in favour of group B (−4⋅2 versus −11⋅2; P = 0⋅037)
(Fig. 4).
There was no significant difference in generic
EQ-5D-5L™ scores between groups at week 6 (Table 1).
However, there was a significant improvement from base-
line of 14 per cent in group A (P = 0⋅048) but no difference
in Group B (11 per cent improvement; P = 0⋅298).
Table 1 Quality-of-life scores in randomized groups
ICQ score EQ-5D-5L™ score
Group A Group B P* Group A Group B P*
Week 0 47⋅9(16⋅4) 48⋅3(15⋅4) 0⋅942 0⋅56(0⋅16) 0⋅56(0⋅19) 0⋅918
Week 6 43⋅7(15⋅47) 37⋅1(12⋅3) 0⋅174 0⋅64(0⋅14) 0⋅62(0⋅11) 0⋅258
P† 0⋅413 0⋅031 0⋅048 0⋅298
Values are mean(s.d.). Group A, supervised exercise programme (SEP);
group B, SEP and neuromuscular electrical stimulation. ICQ, Intermittent
Claudication Questionnaire; EQ-5D-5L™, EuroQoL Five Dimensions
five-level instrument. *Paired t test; †unpaired t test.
Fig. 4 Change in disease-specific Intermittent Claudication
Questionnaire scores over 6 weeks in groups A and B
*
10
0 the 17 patients who completed the study protocol; they
ICQ score
–10
–20
–30
–40
Group A Group B
Individual and mean(s.d.) values are shown. ICQ, Intermittent Claudica-
tion Questionnaire. *P = 0⋅037 (unpaired t test).
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Published by John Wiley & Sons Ltd
361
Ultrasound measurements
There were no significant changes in superficial femoral
artery diameter within or between groups at week 0 or week
6 (Table S4, supporting information).
Resting blood volume flow assessment did not show any
significant difference within groups, or between group A
and group B from week 0 to week 6 (Table S4, support-
ing information). However, at week 6, group B showed
a significant increase in blood volume flow after 15 min
of device use (device on) compared with rest (control)
(P = 0⋅002) and subsequently the opposite on device ces-
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sation (P = 0⋅014).
TAMV increased significantly in group A at rest between
week 0 and week 6 (1⋅84 cm/s; P = 0⋅025), whereas there
was no significant change in group B. There was a sig-
nificant difference in the change in TAMV at rest over
6 weeks between groups (–3⋅77 cm/s; P = 0⋅022). Six-week
analysis in group B showed that TAMV increased sig-
nificantly with the device on at 15 min compared with
rest (control) (4⋅52 cm/s; P < 0⋅001) (Table S5, support-
ing information). Subsequently, there was a significant
decrease in TAMV on device cessation (–3⋅25 cm/s;
P = 0⋅018).
Laser Doppler flowmetry
Group A showed significant improvements in resting blood
flux after 6 weeks of SEP only in the hand (median differ-
ence 21⋅30 AU; P = 0⋅024) and foot (10⋅60 AU; P = 0⋅026),
but this was not the case for temperature measurements
(Table S6, supporting information).
In group B, there was a significant improvement in blood
flux at the foot while the device was on between week 0
and week 6 (45⋅70 AU; P = 0⋅022) (Table S7, supporting
information). However, resting temperature and blood flux
in the hand and foot were not significantly different at rest
over 6 weeks.
Compliance
Analysis of the NMES device use compliance diary in
group B showed 96 (range 90–100) per cent adherence in
reported good tolerance of device use within their daily
routine.
Discussion
This article describes a pilot study and then an RCT assess-
ing the impact of NMES on IC. The pilot study showed
that a footplate NMES device can improve functional
capacity for both MCD and ICD in patients with IC. The
www.bjs.co.uk BJS 2020; 107: 355–363
362
RCT found a significant adjunctive benefit of NMES to
SEP alone for ICD.
Both generic and disease-specific QoL scores improved
significantly in the proof-of-concept study, and ICQ
also improved significantly in the NMES group of the
RCT. After 6 weeks there was a significant difference in
disease-specific QoL improvement between the groups,
with a 23 per cent improvement in ICQ score when addi-
tional NMES was used, compared with 9 per cent in the
SEP-only group.
Although limited by incomplete recruitment to the RCT,
considering both studies together, NMES as a management
strategy for patients with IC can improve both functional
capabilities and QoL that is limited by IC, beyond that of
standard SEP therapy.
Haemodynamic studies were performed as a mecha-
nistic evaluation of changes attributable to the footplate
NMES device. In each of the studies there was a sig-
nificant increase in blood volume flow and TAMV with
the device on at both week 0 and week 6, but this was
not maintained when the device was turned off. This sup-
ports a direct relationship between the NMES-triggered
calf muscle contraction and improved arterial flow to
the leg.
Over the past 30 years there has been limited research
regarding NMES for PAD, with a heterogeneity of proto-
cols, lack of standardization of electrical parameters and use
of different medical devices. Inferences from these studies,
however, suggested beneficial functional and haemody-
namic effects of lower limb NMES in patients with IC. In
1994, Tsang and colleagues21 showed significant improve-
ments in ICD and MCD in 13 patients with stable claudi-
cation with use of a Medi-compex device (Medi-compex,
Switzerland) stimulating the popliteal and anterior tibial
nerve directly for 20 min, three times daily for 4 weeks.
More recently, Ellul and co-workers22 reported a 137-m
(141 per cent; P < 0⋅001) improvement in absolute clau-
dication distance in a prospective pretest–post-test study
of 40 diabetic patients with claudication using direct calf
muscle stimulation with the Veinoplus® device (Ad Rem
Technology, Paris, France) for 60 min daily over 12 weeks.
Abraham et al.23 found a 240 per cent increase (P < 0⋅010)
in lower limb femoral arterial blood flow measured by
duplex ultrasonography in 15 patients with stable IC using
the directly stimulating Veinoplus® device over the calf
muscle mass.
Supervised exercise is clinically effective, but inacces-
sible to many patients, and poor adherence is a com-
mon drawback8,9,11 – 13 . Compliance with intervention is an
important aspect of the successful management of PAD;
in the present studies, compliance with NMES device use
© 2020 BJS Society Ltd
Published by John Wiley & Sons Ltd
A. Babber, R. Ravikumar, S. Onida, T. R. A. Lane and A. H. Davies
was 97 and 96 per cent, with good ability to tolerate
the device.
With the significant changes demonstrated with
once-daily use of NMES for a 30-min session over
6 weeks, a dosing study to assess the impact of a longer
duration or more daily NMES sessions would be reason-
able. This would allow direct comparisons to be made
with the functional changes seen following SEP for 2 h
weekly for a total duration of 3 months, as recommended
by NICE6 .
The main limitation of the RCT was that the target sam-
Downloaded from https://academic.oup.com/bjs/article/107/4/355/6120903 by guest on 29 March 2021
ple size was not achieved because of the limited recruitment
period. A large proportion of patients were ineligible owing
to diabetes, an initial exclusion criterion. After amend-
ment of the inclusion criteria with ethical approval, dia-
betic patients were included in the study, with recruit-
ment of three patients before the study closed. In addi-
tion, three patients (1 from group A, 2 from group B) did
not attend the 6-week follow-up appointment. No adverse
events were reported. A further limitation was an absolute
reliance on patient diaries to record device use and fre-
quency. Unfortunately, an electronic data logger for this
device was not available. This is a consideration for change
for future studies.
Despite the limitations of this study, the positive func-
tional and QoL changes were both statistically and
clinically significant. The improved lower limb arterial
haemodynamics with a footplate NMES device warrants
investigation. NMES could become a viable alternative
to the current clinically effective but underfunded and
underutilized SEPs.
Acknowledgements
The authors thank physiotherapy department staff, Char-
ing Cross Hospital, Imperial College Healthcare Foun-
dation NHS Trust, London, UK, for coordinating the
SEPs and appointments for study participants to ensure
completion of the study protocol. Actegy, UK, provided
footplate NMES device units, and study funding via an
unrestricted educational grant. The research was further
supported by the National Institute for Health Research
(NIHR) Biomedical Research Centre based at Imperial
College Healthcare NHS Trust and Imperial College
London. S.O. and T.R.A.L. are supported by an NIHR
Clinical Lectureship and acknowledge support from the
NIHR Imperial Biomedical Research Centre. The views
expressed are those of the authors, and not necessar-
ily those of the NHS, NIHR or the Department of
Health.
www.bjs.co.uk BJS 2020; 107: 355–363
Footplate neuromuscular electrical stimulation in peripheral artery disease
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