Title: Mechanisms of action study: plantar heel pain
Funder: Health Education England

Abstract: Background PHP is a prevalent and painful condition affecting 1 in 10 people aged over 50. Around half of sufferers will still have symptoms 10 years after they started and so it has a significant health and socio-economic impact. While several treatment options are currently used including exercises and orthothes, no one intervention demonstrates significant superiority in improving pain and function.The need to find the best treatments for PHP has been identified as a priority for the National Institute for Health Research (NIHR) who have funded TREADON, a multi-centre randomised controlled trial to evaluate the comparative treatment effects in PHP between four treatment arms: (i) self-management and advice (SMA); (ii) exercises; (iii) shoe insoles; and (iv) a combination of exercises and insoles. Mechanistic theory underpinning exercise and orthotic devices includes altered muscle function, biomechanics, foot posture and soft tissue structures, however, the exact mechanism is unclear. This additional knowledge would help us better evaluate the treatment effects in the TREADON trial and facilitate future evaluation of more precise treatments. Aim To describe the mechanisms of action of the TREADON trial treatments . The secondary aim is to explore the correlation between the mechanisms and treatment outcomes. Objectives In the four treatment arms we will describe changes in: muscle strength; calf, great toe, lesser toes ankle range of motion gait parameters; heel pressure and gait speed foot posture; navicular height and Foot Posture Index (FPI) imaging features; bone marrow oedema, soft tissue inflammation and plantar fascia thicknessWe will also explore the relationship between mechanisms of action and treatment outcomes through mediation analysis.Methods/timelines for deliveryThis project consists of two work packages. Work package 1: Mechanisms of action nested study. (Months 3-33) We will recruit 120 participants from the TREADON trial (30 participants from each of the four treatment arms) and conduct clinical assessment, gait analysis and MRIs at baseline and at 12 weeks. From this data, we will explore the hypotheses of how each treatment arm achieves its affect. Work package 2: Mediation Analysis(Month 33-39) By pooling the data across all treatment arms, we will undertake causal mediation analysis using structural equational modelling (SEM) to establish direct and indirect effects of gait, muscle and mechanical variables on pain. We will explore if the treatment effect on pain is mediated by any of these factors across treatments, in order to provide more targeted treatments.Anticipated impactUnderstanding the mechanism of action of common PHP treatments, is an important step in understanding this condition. It has the potential to inform a more cost-effective and precise approach to treatment, not only for PHP, but other conditions treated with exercise and orthoses. Dissemination The dissemination strategy will be finalised in collaboration with PPIE representatives, academic supervisors and our communications team. It will be developed to target the different audiences, including patients and the public, academic community, relevant professional and special interest groups, conferences and social media.

Lay abstract: Background Plantar heel pain (PHP)- often called plantar fasciitis, is one of the most common causes of foot pain, affecting one in ten people over the age of 50. People with PHP pain often report pain on taking their first steps after getting out of bed in the morning. While this pain may reduce after getting up and walking around, for many people with PHP the pain remains, limiting their physical activity and impacting on their quality of life. There are a number of treatments for PHP but no single treatment has been shown to be more effective than the others. The need to find the best treatments for PHP has been identified as a priority for the National Institute for Health Research (NIHR) who have funded TREADON (TReatments of Exercise AnD Orthotic devices for plaNtar heel pain), a large UK wide study to compare the effect of commonly used PHP treatments: (i) self-management and advice (SMA); (ii) exercises; (iii) shoe insoles; and (iv) a combination of exercises and insoles. TREADON will recruit up to 696 people with PHP who will be randomly assigned to one of the treatment groups: this means that everyone have an equal chance to be selected into each group. It would be useful to understand how these treatments actually work- this is known as a 'mechanism of action' (MOA) study. These studies are important as through understanding how pain is reduced be it through strengthening the muscles, taking strain off the arch, reducing pressure on the heel bone or improving how people walk (gait), we will be able to develop more effective treatments for PHP. AimThe aim of this research is to describe the mechanisms by which common treatments used in PHP work using muscle strength testing, gait assessment and magnetic resonance imaging (MRI). Design and methodsThis research consists of two work packages Work package 1 (WP1): Mechanism of action study.People who have been recruited into TREADON in the Yorkshire region will be invited to participate in the mechanism of action study. It will be completely voluntary. For those who agree, they will be invited to Chapel Allerton Hospital in Leeds, before receiving treatment in NHS physiotherapy/podiatry services within six weeks of randomisation, to undergo a gait and muscle assessment and also have an MRI (lasting two hours in total) and undergo the same assessments 12 weeks after they receive their treatment. Given our previous experience in undertaking similar studies, we aim to recruit 120 people.Work package 2 (WP2): Factors that affect all treatments Once we obtain all data from WP1, we will be able to combine the data to explore if there are any factors which are important across all treatments that improve pain. Patient and public involvement and engagement (PPIE)This application has been developed in partnership with two PPIE groups: TREADON: co-designed the trial and have been instrumental in study design, recruitment and dissemination strategies Leeds BRC: co-designed the Yorkshire sub study Activities included in the Fellowship will be overseen by a Patient Advisory Group (PAG). Dissemination The public and academic dissemination strategy will be finalised in collaboration with PAG and my supervisors and will include: Regular newsletter to inform participants of study progress Participant thank you letter Presentations in public and community events Presentation at academic, professional, public and patient conferences Public and community facing study website, containing sections for patients, healthcare practitioners and links to appropriate evidence-based treatment resources Publish results in appropriate peer-reviewed journals Working with BRC communications officer to develop a wide public dissemination strategy Utilise social media to promote research progress and results

Research activity codes: 6.3 MEDICAL DEVICES;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL