Title: Evaluating Shockwave therapy Of Lower Extremity diabetic Foot ULcers (SOLEFUL)
Funder: Department of Health and Social Care

Abstract: Background:Diabetes affects over 4.5 million people in the UK, a quarter of whom develop a diabetic foot ulcer (DFU). 40% of DFU take over 3 months to heal and 20% more than a year, resulting in poor patient quality of life and costs the NHS 1 billion/year(1). Extracorporeal Shockwave Therapy (ESWT) is a potentially efficacious, non-invasive novel intervention to augment DFU healing compared to current care. However, the clinical effectiveness and optimum dose are unknown(2). This fellowship programme will address the knowledge gap and equip me with the expertise to progress towards becoming a leader in diabetic foot research. Aims Critically evaluate the evidence of ESWT for DFU healing to identify knowledge gaps Pilot the proposed randomised controlled trial (RCT) of ESWT for DFU healing Understand patient and clinician perceptions and experience of the trial and ESWT Develop a model-based cost utility analysisMethodsSystematic ReviewI will update my systemic review and meta-analysis of randomised control trials comparing to ESWT to standard ulcer care +/- sham ESWT for DFU healing, including Synder et al trial and my own findings. The primary outcome will be time to healing. Secondary outcomes will be any other ulcer related parameters. I will combine results of the latest studies in a meta-analysis. I will undertake subgroup analysis to investigate the effect of shockwave dosage on healing. This will identify the current gaps in the literature and increase my experience/expertise in conducting systematic reviews and meta-analyses. Pilot TrialI will undertake a pilot RCT to assess scalability and cohesivity of the planned trial elements, co-designed by the PPI group. This single centre trial will recruit 90 participants who will be randomised to 1 of 3 intervention arms (sham, low dose or high dose ESWT), in addition to standard care. The primary outcome is workability of trial elements. Secondary outcomes include time to healing, number of ulcers healed at 6 months, change in patient-reported quality of life and adverse events. Qualitative InterviewsI will conduct semi-structured in-depth interviews with 3 groups: Participants who have undergone ESWT to explore their trial/ESWT experience and opinions Eligible patients who did not take participate in the trial to explore reasons for declining. Clinicians to explore their perceptions towards ESWT.Economic ModelI will produce an economic model that can estimate resource use and quality adjusted survival associated with ESWT for DFU. Timeline for Delivery This programme of work is vital to progress the evidence base of ESWT for DFU and once the completed will support undertaking the main trial. The outcomes will be presented to clinicians and policymakers to influence clinical guidelines to recommend use of ESWT as an adjunct to DFU healing in routine care. I aim to be in position to support its use in routine care, and therefore deliver patient benefit, in 5 years. Anticipated Impact and DisseminationOutputs will be presented scientific conferences, published in peer review journals and disseminated to the public and patients via newsletters and posters, as guided by the PPI group.

Lay abstract: Summary of the problem:Diabetes has been described as the fastest growing health crisis of our time. It currently affects more than 4.5million people in the UK. The direct cost to the NHS is already over 1 billion per year. One of the commonest complications of diabetes are foot ulcers. Despite current best treatment, these ulcers can be very difficult to heal, often taking months to heal and some never do. Even after healing ulcers return in up to 60% of people. In England someone undergoes an amputation of part of their foot every 2 hours and every 4 hours someone loses their leg due to diabetic foot ulcers. People are rarely able to be as active as before. This seriously affects their work, finances and quality of life.Research into improved treatments are a national priority. These treatments need to be safe, effective, tolerable for patients and value for money.My preliminary research has identified shockwave therapy as a promising new treatment in which high-power soundwaves (similar to ultrasound) are delivered to the ulcer. This may make ulcers heal faster. However, the effectiveness of shockwave therapy and the optimum dose is unknown. What I aim to do: To review the scientific literature for the available evidence regarding shockwave therapy in diabetic foot ulcers To carry out a preliminary (pilot) trial comparing sham (not active) shockwaves, low number of shockwaves and high number of shockwaves on diabetic foot ulcer healing To understand beliefs, concerns, ideas and experience of shockwave therapy amongst patients and clinicians To investigate the cost effectiveness (value for money) of shockwave therapy Methods Literature review:I will systematically summarise and critically appraise the current evidence on shockwave therapy for diabetic foot ulcers by searching the research databases, journals and contacting shockwave companies. This will identify gaps in the research. Pilot Trial:Ninety patients with DFU will be randomly assigned to one of three treatment groups:1. High dose shockwave treatment2. Low dose shockwave treatment3. 'Sham' shockwave treatmentEach treatment will be delivered in 3x30minute sessions in a 7-day period.Face-to-face follow up appointments will take place 1, 2, 3 and 6 months after treatment to measure ulcer healing and changes in quality-of-life. Interviews:I will undertake interviews to explore patient opinion of shockwave therapy, experience in taking part in the trial, reasons patients do not want to take part and clinician attitudes to shockwave therapy.12 patients and 8 clinicians will be invited to take part. Value for MoneyI will evaluate if shockwave therapy for DFU represents value for money using results from the trial and the existing evidence. Who has been involved so far:Co-design and co-production are central to the design of this fellowship. Patients with diabetes from the Hull Diabetic Foot Research Advisory Group have directly informed the design of the proposed research, prioritised the importance of different outcomes, how often to give shockwave therapy and provided feedback about managing appointments. They will continue to be actively involved throughout the proposed research, specifically developing information of patients, helping to manage the trial, interpreting results from the interviews and devising an impactful dissemination plan. Experts in research design from the York Trials Unit have advised extensively on my research plans. Plans to publicise my research findings:Informed by our patient group, initial ideas include:1. A newsletter for participants and their medical practitioners2. Posters in waiting areas of vascular and diabetic foot clinics3. A summary of results for charity and support group websites and newsletters4. Presentation at medical conferences and publication in medical journals.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: METABOLIC AND ENDOCRINE;SKIN