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

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Intermittent Claudication
• Intervention / Treatment: Device: Active TENS; Device: Placebo TENS; Behavioral: Patient-Centred Education

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?

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Strathcylde
    • Glasgow, Strathcylde, United Kingdom, G51 4TF
      • Clinical Research Facility, Queen Elizabeth University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active TENS; 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; 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.; Other Names: TENS; TNS; Transcutaneous Electrical Nerve Stimulation; Transcutaneous Nerve Stimulation
PLACEBO_COMPARATOR: Placebo TENS; 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; TENS device use with setting so that the stimulation delivered is ineffective; Other Names: P-TENS; Placebo Transcutaneous Electrical Nerve Stimulation
EXPERIMENTAL: Patient-Centred Education; 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; Group education for patients with peripheral arterial disease and intermittent claudication about their condition, improving patient ownership, and promoting self-managed walking; Other Names: Education; SEDRIC; Structured patient-centred education intervention
EXPERIMENTAL: Patient-Centred Education + Active TENS; Combination of Patient-Centred Education arm and Active TENS arm.	Device: Active TENS; 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.; Other Names: TENS; TNS; Transcutaneous Electrical Nerve Stimulation; Transcutaneous Nerve Stimulation; Behavioral: Patient-Centred Education; Group education for patients with peripheral arterial disease and intermittent claudication about their condition, improving patient ownership, and promoting self-managed walking; Other Names: Education; SEDRIC; Structured patient-centred education intervention

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Glasgow Caledonian University
• Collaborators: Northumbria University; NHS Greater Glasgow and Clyde; University of Glasgow; Chief Scientist Office of the Scottish Government
• Investigators: Study Director: Chris Seenan, PT, PhD, Glasgow Caledonian University; Principal Investigator: UKACHUKWU ABARAOGU, MSc, PT, Glasgow Caledonian University; Study Chair: Julie Brittenden, MD, FRCS, Queen Elizabeth University Hospital/University of Glasgow

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2017
• Primary Completion (ACTUAL): March 24, 2020
• Study Completion (ACTUAL): March 24, 2020

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (ACTUAL): July 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Feasibility; Physical activity; Pain management; Patient education; Transcutaneous electrical nerve stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication
• Other Study ID Numbers: 16 044

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