Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001383853
Ethics application status
Approved
Date submitted
30/08/2021
Date registered
14/10/2021
Date last updated
27/10/2024
Date data sharing statement initially provided
14/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Foot-PAD trial: Effect of a footplate muscle stimulation program on walking capacity in people with Peripheral Artery Disease.
Scientific title
A single-centre, double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based program of footplate neuromuscular electrical stimulation on walking capacity in people with peripheral artery disease.
Secondary ID [1] 305513 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Foot-PAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
peripheral artery disease 323450 0
intermittent claudication 323451 0
Condition category
Condition code
Cardiovascular 321001 321001 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Footplate-NMES (intervention condition). 12-week home-based program using a footplate-NMES device (Revitive® Medic Coach). Participants will experience a range of sensations from light tingling and feelings of pins and needles, to noticeable muscle twitches and contractions in the muscles of the feet and legs. The active device is used 2x30 min periods each day to deliver stimulation sufficient to induce contraction of the leg (calf) muscles.
The Revitive® Medic Coach is a disc-shaped footplate NMES device that provides pre-programmed electrical stimulation to the plantar aspect of the feet to activate the muscles of the feet and calf. The device is designed to be used whilst in a seated position, with the device placed on the floor. The intensity of electrical stimulus can be varied from 0 to 99. Participants will initially complete a 45 min familiarisation session with an unblinded member of the study team (participant support assistant). When first using the NMES device at the familiarisation visit, baseline sensory and motor thresholds will be established by systematically increasing the stimulation intensity in increments of one unit whilst the participant provides verbal sensory feedback. The minimal intensity, at which the participant is able to clearly feel electrical stimulation, will be recorded as the sensory threshold; and that producing visible muscle twitches will be the motor threshold. The stimulation intensity will be adjusted to produce visible but non-painful contraction of the lower limb musculature at twice the individual motor threshold or as much as the participant can tolerate as comfortable, whichever is greater (i.e. the therapy target threshold). Participants will be encouraged increase the intensity of the NMES intervention as tolerated throughout the intervention period. Compliance with intervention device use will be assessed with daily diary and automated device data logging via a smart-phone App.
Intervention code [1] 321576 0
Treatment: Devices
Intervention code [2] 321577 0
Rehabilitation
Comparator / control treatment
Footplate-PLACEBO (control condition). 12-week home-based program using a placebo control footplate device. The placebo device is used 2x30 min periods each day to deliver a transient stimulation which starts at a low intensity and titrates to zero. Participants will experience the same range of sensations as the active arm of the trial, from light tingling and feelings of pins and needles, to noticeable muscle twitches, except that the control stimulus is not sufficient to induce contraction of the leg (calf) muscles.
Control group
Placebo

Outcomes
Primary outcome [1] 328782 0
Six-minute walk test (6MWT). Change in maximum walking distance (MWD) during the 6MWT.
Timepoint [1] 328782 0
Week 0 (baseline), week 6, week 12 (primary), and week 18.
Secondary outcome [1] 400308 0
Change in pain-free walking distance (PFWD) during the 6MWT.
Timepoint [1] 400308 0
Week 0 (baseline), week 6, week 12, and week 18.
Secondary outcome [2] 400309 0
Self reported walking capacity measured using the Walking Impairment Questionnaire (WIQ)
Timepoint [2] 400309 0
Weeks 0 (baseline), 6, 12, and 18.
Secondary outcome [3] 400310 0
Disease specific quality of life assessed using the Intermittent Claudication Questionnaire.
Timepoint [3] 400310 0
Weeks 0 (baseline), 6, 12, and 18.
Secondary outcome [4] 400311 0
Maximum walk time (MWT) measured during a graded treadmill walking test (Gardner-Skinner protocol).
Timepoint [4] 400311 0
Weeks 0 (baseline), 12, and 18
Secondary outcome [5] 400312 0
Physical activity levels objectively assessed using an activPAL accelerometer (PAL Technologies Ltd, Glasgow, United Kingdom).
Timepoint [5] 400312 0
Weeks 0 (baseline), 12 and 18.
Secondary outcome [6] 400313 0
Ankle to brachial systolic blood pressure index (ABI) of both legs (exploratory outcome).
Timepoint [6] 400313 0
Weeks 0 (baseline), 12, and 18.
Secondary outcome [7] 400314 0
Limb blood flow (measured with strain gauge plethysmography) measured at rest and during reactive hyperaemia in both legs (exploratory outcome).
Timepoint [7] 400314 0
Weeks 0 (baseline), 12, and 18.
Secondary outcome [8] 400315 0
Symptom severity and impact measured with the claudication symptom instrument (CSI) (exploratory outcome).
Timepoint [8] 400315 0
Weeks 0 (baseline), 1, 3, 6, 9, 12, and 18.
Secondary outcome [9] 400316 0
Symptom impact measured using the Revitive® smart-phone App. This question will be presented to participants every two weeks during the intervention period (exploratory outcome).
Timepoint [9] 400316 0
Weeks 0 (baseline),2,4,6,8,10, and 12.
Secondary outcome [10] 400317 0
Device experience questionnaire to determine the ease of using the device and perceived device efficacy. Tool designed for this trial. (exploratory outcome). This tool will be completed at the end of weeks 1 and 12 only.
Timepoint [10] 400317 0
Weeks 1 and 12.
Secondary outcome [11] 400318 0
Compliance with intervention device use. Participants will be asked to maintain a diary of device use where they record the date, time, duration, intensity range, and any relevant comments for each session of device use. Device use data will also be automatically captured and logged by the Revitive® smart-phone App,
Timepoint [11] 400318 0
Weeks 0 (baseline), 6, 12.
Secondary outcome [12] 400319 0
Safety. Serious adverse events (SAEs) and adverse events of special interest (i.e. where there may be a causal association with the study intervention or the disease being studied) will be assessed using a study-specific grading form based on cTCAE v5.
Timepoint [12] 400319 0
Weeks 0 (baseline), 6, 12, 18.
Secondary outcome [13] 401012 0
Initial claudication time (pain-free walking time, PFWT) measured during a graded treadmill walking test (Gardner-Skinner protocol).
Timepoint [13] 401012 0
Weeks 0 (baseline), 12, and 18.
Secondary outcome [14] 401013 0
Tissue oxygenation (measured with near infrared spectroscopy) measured at rest and during reactive hyperaemia in both legs (exploratory outcome).
Timepoint [14] 401013 0
Weeks 0 (baseline), 12, and 18.
Secondary outcome [15] 401014 0
Symptom severity and impact measured with a visual analogue scale (exploratory outcome).
Timepoint [15] 401014 0
Weeks 0 (baseline), 1, 3, 6, 9, 12, and 18.

Eligibility
Key inclusion criteria
1. Clinical diagnosis of PAD with intermittent claudication by a vascular surgeon, confirmed with 1) positive Edinburgh Claudication Questionnaire; and 2) resting ABI less than 0.9; OR positive walking claudication test (fall in ankle pressure greater than 30mmHg (or 20%), following treadmill walking test).
2. 18 years of age or older.
3. Able to understand and communicate in English sufficient to complete the informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Walking distance limited by symptoms other than claudication / leg discomfort during initial treadmill screening walking test.
2. Critical limb ischaemia including rest-pain, arterial ulcers (tissue loss) or gangrene.
3. Severe disease requiring surgical or endovascular intervention.
4. Previous lower limb or foot amputation.
5. Plantar wounds, including broken or bleeding skin, or ulcers.
6. Any implanted electronic, cardiac or defibrillator device.
7. Being treated for lower limb deep vein thrombosis (DVT) or potential presence of DVT based on presentation.
8. Pregnant or intending to become pregnant during trial period.
9. Has participated in a supervised exercise program within the previous three-month period.
10. Has used any form of lower limb neuromuscular electrical stimulation therapy within the previous three-month period.
11. Has previously used at any time a Revitive footplate neuromuscular stimulation device.
12. Unwilling or unable to engage with the technology required for the intervention, inc. the need for WiFi internet access.
13. Terminal illness or other medical condition that may affect the ability to complete the trial, or deemed unfit to undertake the trial procedures by the trial medical practitioner (e.g. where walking tests may be contraindicated because of existing or unstable medical condition that may be made worse or exacerbated by participation).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be ensured using a centralised computer allocation service (SealedEnvelope.com).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur when the participant has completed all baseline measurements (week 4). Randomisation will be conducted using a secure, independent web-based randomisation system (SealedEnvelope.com) without stratification. Randomisation will be in a 1:1 ratio and randomisation blocks of 4-8 participants will be used to ensure equal group numbers throughout the recruitment and enrolment period.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
The Foot-PAD trial is a single centre, parallel group, double-blind, randomised placebo-controlled study that compares the effectiveness of a daily home program of footplate neuromuscular stimulation (Revitive® Medic Coach, Footplate-NMES) with a placebo-control intervention (Footplate-PCON). All eligible participants will continue to receive usual care and medical advice from their local doctor and vascular surgeon, and they will be randomly allocated to the NMES (intervention) or PCON (placebo control) programs for 12 weeks. Outcome measures will be assessed at baseline (week 0), midway through (week 6) and at the end of the intervention period (week 12), and again at the end of the 6-week off-intervention phase (week 18).
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Previous trials in this area indicate a potential effect of 30m with a standard deviation of 90m for six-minute walk test distance. This provides a small effect size of 0.33. With a required power of 80%, alpha of 0.05, measurements at 2 time points (Baseline and week 12) an expected correlation over time of 0.7, and an expected effect size of 0.33, and based on a linear mixed effects model, 74 participants would be required in each group. Allowing for ~18% dropout, 90 participants will be recruited in each group.

Data will be analysed using Stata 16 software. The change from baseline in walk distance will be analysed using a linear mixed model with factors for treatment group (2 levels: NMES, PCON), time (2 levels: week 6, week 12), treatment-by-group interaction term, and subject as a random effect. Baseline walk distance will be included as a covariate, as will a term for the baseline-by-time interaction so that the stronger correlation between baseline and the earlier timepoint (Week 6) does not over-emphasise the baseline covariate and then over-correct at Week 12. Inclusion of the treatment-by-time interaction gives full flexibility in having different treatment effects at 6-weeks and 12-weeks and thus enable estimates of active vs sham to be obtained at both the 6-week and 12-week timepoints. The primary comparison will be NMES vs PCON at the 12-week timepoint. The comparison of NMES vs PCOON at the 6-week timepoint is a secondary endpoint.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/02/2022
Actual
23/02/2022
Date of last participant enrolment
Anticipated
1/10/2024
Actual
31/05/2024
Date of last data collection
Anticipated
1/11/2024
Actual
16/10/2024
Sample size
Target
180
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 20434 0
The Sunshine Coast Private Hospital - Buderim
Recruitment hospital [2] 20435 0
University of the Sunshine Coast Clinical Trials Centre - Sippy Downs - Sippy Downs
Recruitment hospital [3] 20436 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment hospital [4] 25087 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 35201 0
4556 - Buderim
Recruitment postcode(s) [2] 35202 0
4556 - Sippy Downs
Recruitment postcode(s) [3] 40756 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 309562 0
Commercial sector/Industry
Name [1] 309562 0
Actegy Pty Ltd
Country [1] 309562 0
Australia
Primary sponsor type
University
Name
University of the Sunshine Coast
Address
90 Sippy Downs Drive, Sippy Downs QLD 4556 Australia.
Country
Australia
Secondary sponsor category [1] 310563 0
None
Name [1] 310563 0
Address [1] 310563 0
Country [1] 310563 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309342 0
The Prince Charles Hospital (TPCH HREC)
Ethics committee address [1] 309342 0
Ethics committee country [1] 309342 0
Australia
Date submitted for ethics approval [1] 309342 0
08/09/2021
Approval date [1] 309342 0
05/10/2021
Ethics approval number [1] 309342 0
78962
Ethics committee name [2] 309612 0
University of the Sunshine Coast (USC HREC)
Ethics committee address [2] 309612 0
Ethics committee country [2] 309612 0
Australia
Date submitted for ethics approval [2] 309612 0
13/10/2021
Approval date [2] 309612 0
Ethics approval number [2] 309612 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113834 0
Prof Christopher Askew
Address 113834 0
University of the Sunshine Coast, School of Health and Behavioural Sciences.
90 Sippy Downs Drive, Sippy Downs QLD 4556 Australia.
Country 113834 0
Australia
Phone 113834 0
+61 412 332 987
Fax 113834 0
Email 113834 0
[email protected]
Contact person for public queries
Name 113835 0
Mark Windsor
Address 113835 0
University of the Sunshine Coast, School of Health and Behavioural Sciences.
90 Sippy Downs Drive, Sippy Downs QLD 4556 Australia.
Country 113835 0
Australia
Phone 113835 0
+61 413 827 628
Fax 113835 0
Email 113835 0
[email protected]
Contact person for scientific queries
Name 113836 0
Christopher Askew
Address 113836 0
University of the Sunshine Coast, School of Health and Behavioural Sciences.
90 Sippy Downs Drive, Sippy Downs QLD 4556 Australia.
Country 113836 0
Australia
Phone 113836 0
+61 412 332 987
Fax 113836 0
Email 113836 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Commercial research funding agreement does not permit data sharing.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13026Study protocol  [email protected]
23962Statistical analysis plan https://doi.org/10.25907/00855[email protected]



Results publications and other study-related documents

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