Pain Management and Patient Education for Physical Activity in Intermittent Claudication (PrEPAID)

Study Overview
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Brief Summary
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Peripheral Arterial disease is a common condition which causes narrowing of the arteries. The most common symptom that patients with PAD experience is Intermittent Claudication (IC), pain in the lower limb(s) on exertion, which is relieved by rest. IC reduces patients' quality of life (QoL) by limiting their ability to walk and engage in daily activities. Regular exercise and physical activity (PA) are central to the management of PAD and help to improve walking distances and reduce the risks associated with PAD such as heart attack and stroke. However, exercise and PA in this population is often limited due to pain. Investigators have shown that Transcutaneous Electrical Nerve Stimulation (TENS) can help to reduce pain and increase walking distance in patients with PAD. Investigators have also shown that educating patients about their condition and helping them to set goals has the potential to increase PA, and quality of life. This study will examine the feasibility of designing a definitive trial that investigates whether TENS can improve the physical activity of patients with PAD when delivered alone and/or alongside a patient education programme.

Detailed Description
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Peripheral Arterial disease (PAD) affects 2.7 million people in the United Kingdom (UK). The most common symptom that patients experience is Intermittent Claudication (IC), which is pain in the buttock, calf or thigh precipitated by exercise and relieved by rest. The underlying cause of PAD is atherosclerosis, which leads to arterial stenosis, inadequate blood flow and build-up of lactic acid during exercise. Patients with IC have impaired quality of life due to reduced physical capacity. Furthermore, due to the diffuse nature of atherosclerosis and the involvement of other arterial beds, they have 3-4 times increased mortality compared to age and sex matched controls. Patients with symptomatic PAD should receive the same secondary prevention management as patients with symptomatic coronary artery disease. Improving daily physical activity (PA) is particularly important in individuals with IC as lower PA levels have been recognised as a strong predictor of increased morbidity and mortality in this population. Current National Institute for Health and Care Excellence (NICE) guidelines recommend the use of supervised exercise programmes (SEPs), encouraging patients to exercise to the point of maximal pain, as first line treatment. SEPs has been shown to be cost-effective when compared to other treatment options such as endovascular intervention and surgical revascularisation. However, while systematic reviews show that SEPs lead to a significant improvement in the absolute walking distances of patients with IC on a treadmill, it is unclear if this is sustained or leads to improvement in daily PA. Furthermore, due to the considerable extra resources required to deliver the recommended 3 months exercise programme (30-45 minutes 3x weekly), SEPs are not always routinely available to National Health Service (NHS) patients, and time and travel costs tend to lead to low patient uptake and high attrition rates. Therefore, investigating the feasibility of using low-cost, patient-centred interventions that can support increased PA is warranted. Lack of self-efficacy, attributed to poor understanding of the disease and uncertainty regarding the importance of exercise, has been shown to be a major barrier to exercise uptake in this population. Educating patients with IC about their disease pathology and the benefits of walking is key to enhancing success of secondary prevention strategies for people with IC. Investigators recently piloted a structured, patient-centred education intervention (SEDRIC) with the specific aim of educating patients with IC about their condition, improving patient ownership, and promoting self-managed walking. In addition to improved treadmill walking distances, investigators found out that there was a trend for patients to increase their daily PA. For patients with IC to gain benefits of secondary prevention, exercising beyond the point when pain occurs is recommended, representing another barrier to engagement in PA. Despite this, investigators' systematic review found that pain management as a route to facilitate exercise and PA has rarely been explored. Recent interest has focused on the use of TENS (a low-cost, non-invasive pain management device) to improve angiogenesis, muscle function, pain and walking distances in patients with IC. TENS has a strong placebo effect in pain conditions, and testing effectiveness against placebo is advocated. In a proof-of-concept pilot study, Investigators demonstrated that TENS could significantly improve pain and increase treadmill walking distances above placebo levels. Our exploratory study also established that home use of TENS was both acceptable and provided self-reported improvement in PA in individuals with IC. Although patient-centred education (SEDRIC) and TENS have both demonstrated potential to improve daily PA in people with IC, the use of these components in combination has not previously been evaluated. Investigators therefore propose a 2 x 2 (TENS versus placebo TENS x SEDRIC versus no additional education) feasibility Randomised Controlled Trial (RCT) that will compare use of TENS against placebo TENS with and without a patient-centred education programme. Investigators have conducted a series of pilot studies underpinning both aspects of the intervention. Investigators have demonstrated in an experimental lower limb ischaemic pain model in healthy volunteers (n=28) that TENS significantly reduced onset of pain (by 29 seconds; 23%), tolerance of pain (by 203 seconds; 53%) and the pain endurance (by 173 seconds; 67%), compared to placebo TENS. Following this, in a proof-of-concept pilot study, investigators demonstrated that TENS when applied to patient with IC exercising on a treadmill (n=40) significantly improved absolute claudication distance (ACD) above placebo levels (approx. mean individual increase in ACD of 40%, p=.025, r= .53). Our phase 2 study also established that home use of TENS was both acceptable and provided self-reported improvement in PA in individuals with IC. Investigators have not assessed the ability of TENS to improve ACD when used during daily life. Similarly, this research group developed and piloted SEDRIC, a structured, patient-centred education intervention with the specific aim of educating patients about their condition, improving patient ownership, and promoting self-managed walking. Investigators found that in patients with PAD (n=14), treadmill walking distances (30%) and quality of life (32%) improved from baseline after 6 weeks of structured education, and there was a trend for patients to increase their daily PA (approx. 8% change from baseline). The aim is to determine the feasibility of electrical stimulation via a low-cost CE-marked device used within a patient centred education programme to improve walking distances in patients with PAD. The following research questions will be answered by this project: What is the feasibility (i.e. recruitment and retention rates, adherence, safety, sample size for a definitive trial, potential for effectiveness) of conducting a definitive RCT comparing TENS with and without patient-centred education? How acceptable are TENS and patient-centred education as interventions on their own or in combination in patients with IC?

Official Title
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Pain Management and Patient Education for Physical Activity in Intermittent Claudication (PrEPAID): Feasibility Randomised Controlled Trial

Conditions
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Peripheral Arterial Disease, Intermittent Claudication

Intervention / Treatment
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* Device: Active TENS
* Behavioral: Patient-Centred Education
* Device: Placebo TENS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of symptomatic Peripheral Arterial Disease (PAD) including resting Ankle Brachial Pressure Index (ABPI) <0.9 in at least one leg Stable IC for ≥3 months Walking limited primarily by claudication Able to exercise on a treadmill Able to read and speak English to a level allowing satisfactory completion of the study procedures Able to provide written informed consent for participation Exclusion Criteria: Planned surgical or endovascular intervention for PAD within the next 3 months Critical limb ischaemia The presence of any absolute contraindications to exercise testing/training as defined by the American College of Sports Medicine (ACSM) Previous experience of using TENS/ structured patient education for PAD Contraindications to TENS (including epilepsy, dermatological conditions, indwelling electrical pumps/pacemakers) and inability to apply TENS independently. Patients who require walking aids including artificial limbs Major surgery, myocardial infarction or stroke/ Transient Ischaemic Attack (TIA) in the previous 6 months Co-morbidities that cause pain or limit walking to a greater extent than IC (e.g. severe arthritis) >20% variation in baseline ACD on treadmill Severe peripheral neuropathies above the ankle. Participation in another research protocol

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2x2 randomised feasibility controlled trial blinded for primary outcome
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active TENS<br>Participants in the TENS groups will be provided with a TENS machine and training at the baseline visit to the Clinical research Facility (CRF). They will be instructed to use it daily as their symptoms require for 6 weeks. The active group will receive High Frequency-TENS (120 Hz, 200µs and a patient-determined intensity of ''strong but comfortable''). | Device: Active TENS<br>* TENS is a form of electrical stimulation that provides symptomatic pain relief that is used extensively within the health-care setting. It is a non-invasive modality; packaged in a small, portable unit that is easy to apply via small electrodes placed on the skin.<br>* Other names: Transcutaneous Electrical Nerve Stimulation;|
| Placebo Comparator: Placebo TENS<br>Placebo TENS : Participants will receive the same model, programmed settings and instructions for use as those in the active group except that the device will be set to an ineffective stimulation (120 Hz, 200µs and a patient-determined intensity of '6mA). For the purpose of blinding, participants will be told that different dosages of TENS are being tested, some of which where the stimulation might not be perceivable even though the device is working. | Device: Placebo TENS<br>* TENS device use with setting so that the stimulation delivered is ineffective<br>* Other names: Placebo Transcutaneous Electrical Nerve Stimulation;|
| Experimental: Patient-Centred Education<br>Patient-Centred Education : a one-off three-hour workshop of structured group education (4-5 persons in each group) and three 2-weekly phone calls. The aim will be to modify patients' illness beliefs and perceptions about IC/PAD by educating them on disease pathology and management philosophy. After the workshop, each patient will be supported to set goals for walking, develop an action plan regarding how these goals will be met and encouraged to repeat this process for each new walking goal. | Behavioral: Patient-Centred Education<br>* Group education for patients with peripheral arterial disease and intermittent claudication about their condition, improving patient ownership, and promoting self-managed walking<br>* Other names: Structured patient-centred education intervention;|
| Experimental: Patient-Centred Education + Active TENS<br>Combination of Patient-Centred Education arm and Active TENS arm. | Device: Active TENS<br>* TENS is a form of electrical stimulation that provides symptomatic pain relief that is used extensively within the health-care setting. It is a non-invasive modality; packaged in a small, portable unit that is easy to apply via small electrodes placed on the skin.<br>* Other names: Transcutaneous Electrical Nerve Stimulation;Behavioral: Patient-Centred Education<br>* Group education for patients with peripheral arterial disease and intermittent claudication about their condition, improving patient ownership, and promoting self-managed walking<br>* Other names: Structured patient-centred education intervention;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Absolute Claudication Distance (ACD) in meters from baseline | Maximal walking distance on graded treadmill test | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Recruitment rates | Measure recruitment rates (ratio of patients who consent to participate to potentially eligible patient recorded via the study screening log | End of study (18 weeks) | 
| Participant retention rate | Ratio of patients who completed the intervention and outcome assessment to the patient who consented | End of study (18 weeks) | 
| Adverse events | Record defined adverse events in all groups | End of study (18 weeks) | 
| Uptake of interventions | Measure uptake of intervention via log of TENS use and attendance at education session and follow up phone calls | End of study (18 weeks) | 
| Qualitative analysis of participant experience of trial | Analysis of focus group discussions with participants regarding experience of trial and interventions | End of study (18 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Initial Claudication Distance (ICD) in meters from baseline | Onset distance of claudication pain on graded treadmill test | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Change in daily physical activity | Total number of steps (activpal step counts) | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Change in daily physical activity | Total number of upright events (activpal upright even count) | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Change in daily physical activity | Total number of walking events (activpal walking event counts) | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Change in daily physical activity | Event-based claudication index (ratio of walking events to upright events) participants undertake in a day. | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Intermittent Claudication Questionnaire (ICQ) | Disease specific quality of life questionnaire | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Short-Form 36 Questionnaire | Generic quality of life questionnaire | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| McGill Pain Questionnaire (MPQ) | Pain quality questionnaire | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Visual Analogue Scale (VAS) | Average Pain intensity in the past 7 days | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Illness Perception Questionnaire (IPQ) | Illness beliefs questionnaire | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Geriatric Depression Scale (Short Form) (GDS-SF) | Depression questionnaire | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Pain Self-Efficacy Questionnaire (PSEQ) | Measure of pain intensity | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 
| Blood biomarkers (optional) | 20mls of blood will be taken from rested subjects, spun and stored for future analysis of markers of angiogenesis and inflammatory response. | Baseline, 6 weeks (post-intervention), 18 weeks (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patient education, Transcutaneous electrical nerve stimulation, Physical activity, Feasibility, Pain management