Title: Development Of a haemophiLia PHysiotherapy INtervention for optimum musculoskeletal health (DOLPHIN) - feasibility of a randomised controlled trial
Funder: Department of Health and Social Care

Abstract: Background: Haemophilia is a rare inherited disorder affecting 1:10,000 of the population, in which the blood does not clot normally, leading to repeated bleeding into joints (haemarthroses) and muscles (haematomas).1 Recurrent haemarthroses trigger a degenerative irreversible process of synovial hypertrophy, articular cartilage and chondral bone erosion. As a result of bleeding during childhood, joints and muscles become painful, swollen and difficult to move (haemophilic arthropathy).2 Health-related quality of life and academic achievement are reduced and are closely associated with the number of bleeding episodes.3-4 Prevention of arthropathy is the major goal of haemophilia treatment and regular prophylactic treatment with missing coagulation factors at an estimated cost per child of &pound;60,000 per annum, has significantly reduced, but not alleviated all joint bleeding. Evidence indicates that children still bleed 1-2 times per year, and the potential for disabling arthropathy remains.5-6 Exercise to increase muscle strength is recommended to improve joint health but there is a lack of robust evidence that this has a significant effect on progression of synovitis and haemophilic arthropathy, or the children's participation in physical activities. Aims and research question: Our aim is to develop a muscle strengthening exercise intervention with potential to improve musculoskeletal health and determine if it is feasible to conduct a clinical trial to test its effectiveness in comparison to usual physiotherapy practice on musculoskeletal health and the progression of haemophilic arthropathy in children with haemophilia. We will carry out a feasibility study to assess key features of study design and project management, including; recruitment and retention rate, willingness of participants to be randomised, exercise adherence, safety and training needs, appropriateness of the outcome measures and explore factors that influence acceptability of the trial and intervention. Plan of investigation: In 3 interlinked studies we will; Develop a muscle strengthening intervention aimed at improving musculoskeletal health and reducing progression of haemophilic arthropathy by systematically reviewing current evidence, consulting clinicians experienced in haemophilia care and children with haemophilia and their families. Conduct a feasibility trial at two UK Haemophilia Centres of the muscle strengthening exercise intervention to usual physiotherapy care. Determine the relevant costs associated with this study in order to carry out an economic evaluation of the exercise intervention. Benefits to patients and the NHS: Disabling physical limitation and pain are the main co-morbidity of haemophilia. One of the important issues for children with haemophilia is participating in games and activities with their friends and for parents of the children it is being able to make informed decisions regarding their child's condition. This research will allow us to design a robust clinical trial of a low cost age-appropriate intervention that enhances musculoskeletal health and minimises bleeding episodes enabling safe participation in games and activities and in the long term improve their well being, quality of life and lessen disability later in life. Information about whether muscle strengthening exercise is safe and beneficial for optimum musculoskeletal health will enable parents to make informed decisions about their child's condition. With treatment costs exceeding &pound;60,000 per year per child and an almost three-fold increase in overall healthcare costs in those with signs of joint arthropathy, by enhancing musculoskeletal health we expect to reduce the individual, medical and societal cost and burden of haemophilia.

Lay abstract: Children are born with haemophilia and only boys are affected. It is a disorder affecting 1:10000 people where the blood does not clot normally, leading to bleeding into muscles and joints. As a result, muscles become weak. Joints become painful and difficult to move. Our recent work shows performance of everyday tasks such as walking, going up and down stairs and balancing on one leg are negatively affected and depend on muscle strength. &ldquo;Being able to participate in games and activities with their friends&rdquo; is one of the things that matters most to boys with haemophilia. At present, there is a lack of evidence that muscle strengthening will have any effect on pain and movement in their joints or help them participate in games and activities with their friends. To evaluate the effectiveness of a muscle strengthening exercise intervention with a randomised controlled trial (RCT) we currently estimate that 104 children would need to be recruited, requiring a large multi-centre trial. The aim of this project is to determine if it is feasible to conduct a full RCT. Firstly, we will develop an optimum exercise intervention by consulting experienced clinicians together with haemophiliac boys and their families. Once developed, we will conduct a feasibility study of 20 boys at 2 sites to assess recruitment potential and retention, exercise adherence, safety and appropriateness of tests to measure outcomes. In addition, we will derive precise estimates of the sample size required and the relevant costs associated with delivering the intervention prior to conducting a clinical trial to test its effectiveness.

Research activity codes: 6.7 PHYSICAL
Health categories: BLOOD