Objectives: The Anti-Freaze-F trial will assess the feasibility of conducting a large randomised controlled trial to assess whether intra-articular injection of anti-TNF (adalimumab) can reduce pain and improve function in people with pain predominant early stage frozen shoulder.
Methods and analysis: We are conducting a multi-centre, randomised feasibility study, with an embedded qualitative sub-study. We will recruit adults ≥18 years with a new episode of shoulder pain attributable to early stage frozen shoulder, recruited from at least five UK NHS musculoskeletal and related physiotherapy services. Participants (n=84) will be randomised (centralised computer generated 1:1 allocation) to receive either: 1) intra-articular injection of anti-TNF (adalimumab 160mg) or 2) placebo injection (saline [0.9% sodium chloride]), both under ultrasound guidance. A second injection of the allocated treatment (adalimumab 80mg) or equivalent volume of placebo will be administered 2-3 weeks later. All participants will receive a physiotherapy advice leaflet providing education and advice about frozen shoulder and pain management. The primary feasibility objectives are: 1) the ability to screen and identify potential participants with pain predominant early stage frozen shoulder; 2) willingness of eligible participants to consent and be randomised to intervention; 3) practicalities of delivering the intervention, including time to first injection and number of participants receiving second injection; 4) standard deviation of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months (i.e. 12 weeks) post-randomisation in order to estimate the sample size for a definitive trial. We will also assess follow up rates and viability of patient-reported outcome measures and range of shoulder motion for a definitive trial. Research Ethics Committee approval (REC 21/NE/0214).
Trial registration number: ISRCTN 27075727; EudraCT number: 2021-003509-23; ClinicalTrials.gov NCT05299242.
Keywords: Adalimumab; Adhesive Capsulitis; Anti-TNF; Frozen Shoulder; Protocol; Randomised Controlled Trial.
Frozen shoulder is a common condition affecting approximately 9% of people aged 25–64 years. During the early phase the pain is usually unbearable and the later restriction in movement is severely limiting. It occurs when the flexible tissue (capsule) that surrounds the shoulder joint becomes inflamed, thickened and tight. It's not fully understood why this happens but it is more common in people with diabetes or Dupuytren's disease, which causes the fingers to curl into the palm. It can also occur following shoulder injury or surgery. The pain can be very severe and lasts 3–9 months, followed by a 4–12 month period of increasing stiffness, after which the condition usually improves. Frozen shoulder often affects a person’s ability to sleep, carry out everyday activities, and work. Current treatments include rest, painkillers, anti-inflammatories, physiotherapy and steroid injections. If stiffness persists, surgery is sometimes recommended. However, there is no evidence that any of these treatments lead to significant benefit in the long term, with many being ineffective. Steroid injections only help in the short term. Adalimumab has been used very successfully to treat other inflammatory diseases such as rheumatoid arthritis. More recently, adalimumab has also been used to treat Dupuytren’s disease, where we found it helps to stop the cells causing the disease and softening and shrinking the diseased diseased tissue. The biological processes underlying frozen shoulder are similar to those in Dupuytren’s disease. The aim of this study is to find out if it is possible to run a larger trial to test whether an injection of adalimumab can reduce pain and prevent the disease from getting worse, if given during the early painful phase of frozen shoulder. We need to conduct this smaller study first to be sure it’s possible to identify and treat people with early-stage frozen shoulder within the current NHS system, before we conduct a much larger trial to find out if this treatment works. In this study we will include 84 adults with painful early stage frozen shoulder who have not yet received treatment. People will be randomised to receive either an injection of the drug adalimumab or a dummy injection of saline (placebo) directly into the shoulder joint, both guided by ultrasound. All participants will also receive standardized advice on how to manage their shoulder pain. We will assess participants before treatment and three months later.
Copyright: © 2023 Hopewell S et al.