Clinical trial NCT03204825: Pain Management and Patient Education for Physical Activity in Intermittent Claudication (PrEPAID)
Official title: Pain Management and Patient Education for Physical Activity in Intermittent Claudication (PrEPAID): Feasibility Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Arterial Disease
Intermittent Claudication
Keywords: Patient education
Pain management
Transcutaneous electrical nerve stimulation
Physical activity
Feasibility
Lead sponsor: Glasgow Caledonian University
Sponsor class: OTHER
Collaborators: name: NHS Greater Glasgow and Clyde
name: University of Glasgow
name: Northumbria University
name: Chief Scientist Office of the Scottish Government
First posted: 2017-07-02
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2x2 randomised feasibility controlled trial blinded for primary outcome
Primary purpose: OTHER

Brief summary: 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: 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:

1. 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?
2. How acceptable are TENS and patient-centred education as interventions on their own or in combination in patients with IC?

Eligibility criteria: 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

Primary outcomes:
measure: Change in Absolute Claudication Distance (ACD) in meters from baseline
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Recruitment rates
timeFrame: End of study (18 weeks)
measure: Participant retention rate
timeFrame: End of study (18 weeks)
measure: Adverse events
timeFrame: End of study (18 weeks)
measure: Uptake of interventions
timeFrame: End of study (18 weeks)
measure: Qualitative analysis of participant experience of trial
timeFrame: End of study (18 weeks)
Secondary outcomes:
measure: Change in Initial Claudication Distance (ICD) in meters from baseline
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Change in daily physical activity
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Change in daily physical activity
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Change in daily physical activity
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Change in daily physical activity
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Intermittent Claudication Questionnaire (ICQ)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Short-Form 36 Questionnaire
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: McGill Pain Questionnaire (MPQ)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Visual Analogue Scale (VAS)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Illness Perception Questionnaire (IPQ)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Geriatric Depression Scale (Short Form) (GDS-SF)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Pain Self-Efficacy Questionnaire (PSEQ)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
measure: Blood biomarkers (optional)
timeFrame: Baseline, 6 weeks (post-intervention), 18 weeks (follow-up)
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility, Queen Elizabeth University Hospital
state: Strathcylde
Study officials:
affiliation: Glasgow Caledonian University
name: Chris Seenan, PT, PhD
role: STUDY_DIRECTOR
affiliation: Glasgow Caledonian University
name: UKACHUKWU ABARAOGU, MSc, PT
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth University Hospital/University of Glasgow
name: Julie Brittenden, MD, FRCS
role: STUDY_CHAIR
References:
citation: Abaraogu UO, Dall PM, Seenan CA. Patient education interventions to improve physical activity in patients with intermittent claudication: a protocol for a systematic mixed-studies review. BMJ Open. 2016 May 20;6(5):e011405. doi: 10.1136/bmjopen-2016-011405.
citation: Tew GA, Humphreys L, Crank H, Hewitt C, Nawaz S, Al-Jundi W, Trender H, Michaels J, Gorely T. The development and pilot randomised controlled trial of a group education programme for promoting walking in people with intermittent claudication. Vasc Med. 2015 Aug;20(4):348-57. doi: 10.1177/1358863X15577857. Epub 2015 Apr 9.
citation: Abaraogu UO, Ezenwankwo EF, Dall PM, Seenan CA. Living a burdensome and demanding life: A qualitative systematic review of the patients experiences of peripheral arterial disease. PLoS One. 2018 Nov 15;13(11):e0207456. doi: 10.1371/journal.pone.0207456. eCollection 2018.
citation: Abaraogu U, Ezenwankwo E, Dall P, Tew G, Stuart W, Brittenden J, Seenan C. Barriers and enablers to walking in individuals with intermittent claudication: A systematic review to conceptualize a relevant and patient-centered program. PLoS One. 2018 Jul 26;13(7):e0201095. doi: 10.1371/journal.pone.0201095. eCollection 2018.
citation: Abaraogu UO, Dall PM, Seenan CA. The Effect of Structured Patient Education on Physical Activity in Patients with Peripheral Arterial Disease and Intermittent Claudication: A Systematic Review. Eur J Vasc Endovasc Surg. 2017 Jul;54(1):58-68. doi: 10.1016/j.ejvs.2017.04.003. Epub 2017 May 18.
citation: Abaraogu UO, Dall PM, Brittenden J, Stuart W, Tew GA, Godwin J, Seenan CA. Efficacy and Feasibility of Pain management and Patient Education for Physical Activity in Intermittent claudication (PrEPAID): protocol for a randomised controlled trial. Trials. 2019 Apr 16;20(1):222. doi: 10.1186/s13063-019-3307-6.