Title: SPiRIT (Shoulder Pain: Randomised trial of Injectable Treatments)A randomised feasibility and pilot study of Autologous Protein Solution (APS) vs Corticosteroids for treating subacromial shoulder pain
Funder: Department of Health and Social Care

Abstract: Research question Is it feasible to conduct a definitive randomised controlled trial to assess the clinical and cost-effectiveness of an Autologous Protein Solution (APS) injection into the subacromial space compared to corticosteroid injections, to manage subacromial pain symptoms? Background Shoulder pain is very common and may be disabling in terms of the patient`s ability to carry out daily activities at home and at the workplace, resulting in time off work. This poses a substantial burden to the individual and society. Shoulder pain does not always have a favourable outcome with current treatments. Evidence for the efficacy of both surgical and non-surgical treatments of shoulder pain is limited. British Elbow and Shoulder Society/British Orthopaedic Association guidelines recommends research into the clinical and cost-effectiveness of injectable treatments for subacromial shoulder pain. Currently, Corticosteroid injections remain the mainstay of initial treatment in the majority of cases of shoulder pain. However, in addition to the lack of strong evidence towards the efficacy of Corticosteroid injections there have also been reports of deleterious effects of corticosteroids on tendon biology. In light of these potential harmful effects, health researchers have been considering alternative pharmacological or bioactive therapies to replace Corticosteroid injections. One such of these is the injection of an Autologous Protein Solution. Autologous Protein Solution is prepared using a single-use device that produces a cell concentrate from autologous blood. The Autologous Protein Solution production process preferentially concentrates anti-inflammatory cytokines production by white blood cells, including IL-1 receptor antagonist and TNF receptor inhibitor. No work currently exists to assess the efficacy of Autologous Protein Solution in treating shoulder pain. Objectives &bull; Record and report recruitment and retention rates from study participants &bull; Obtain estimates for a sample size calculation for a definitive trial &bull; Ensure it is possible to collect appropriate outcomes measures to allow a comprehensive efficacy assessment in a fully powered trial &bull; Ensure it is possible to collect data to furnish a robust cost-effectiveness assessment in a fully powered study Methods Fifty eligible adult patients will be recruited from NHS musculoskeletal-triage centres in England. Patients will be randomised (1:1) and will undergo physiotherapy and ultra-sound guided injection of either Corticosteroid injections or Autologous Protein Solution. Blood collection and preparation of the injections (both Autologous Protein Solution and Corticosteroid injections) will be performed by an independent clinician. The injectable solution will be provided to the radiologist in an opaque syringe to ensure blinding. Timelines for delivery This trial will commence in autumn 2020 and will be conducted over a 25 months period. Anticipated Impact and Dissemination Dissemination will be via conference presentations and publication in high-impact journals. Further, we will ensure links with NICE are established to contribute to NICE recommendations on treatment options for shoulder pain at their scheduled update. We will also ensure a broad public dissemination through use of social media outlets (e.g. twitter) with an explainer video and infographics.

Lay abstract: Shoulder pain is very common, and accounts for thousands of appointments in general practice and hospitals each year in the UK. The most common reason for this pain is inflammation to the tissues just below the outside of the shoulder. Over the years, many different treatments have been tried to treat this pain. The most common treatments that we use currently are steroid injections combined with physiotherapy, or keyhole surgery. Recently, there have been questions about whether using steroid injections is actually safe in the long term. There are concerns that they may affect tendons (the tissue that connect muscles to your bones) or contribute to the development of arthritis. At the same time, some research suggests that our operations may also not be as effective for shoulder pain as previously thought. As such, healthcare workers have to look for other safe and effective treatment options for this painful condition. Laboratory studies have shown that painful shoulders often go together with poor tendon health and inflammation. This had led to recent improvements in injection treatments. These new injections aim to help tendons repair themselves and so reduce inflammation and pain. These are termed 'biologic' injections. Whilst the theory behind these injections is good, and they have been found to be safe, no one has conducted a trial to see if the treatments are more or less effective than steroid injections. We would like to perform a trial to compare one of these biologic-injection treatments against steroid injections. The injection we aim to test involves us taking a sample of the person s blood. We would then take out some of the most useful parts of the blood and inject it back into the shoulder to aid healing. The patient will then receive physiotherapy as normal, regardless of what injection they have. Before we can conduct a full large study, we need to do this smaller study to see how quickly we can recruit patients and whether the patients and doctors are happy with the how the trial works. In this trial we will recruit 50 patients. We will ask patients to join the trial who have already been referred to us for shoulder pain and are about to start normal treatment for this. If they decide to join the trial the only change in their treatment will be the difference in the type of injection they receive. If our study is successful we will then conduct a larger trial to see whether the new type of injection is better than steroids for shoulder pain. If this turns out to be the case then our trials could help large numbers of patients in the NHS with this painful condition.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL