Title: Understanding clinical and patient reported response of children and young people with Cerebral Palsy to Botulinum Toxin A: a longitudinal observational study
Funder: Health Education England

Abstract: Background Cerebral Palsy (CP) is the most common cause of physical disability in childhood. Increased tone (hypertonia) is a significant contributor to secondary impairments impacting on activity and participation. Over the last 20 years intramuscular Botulinum Toxin A (BoNT-A) has become an international standard treatment in the management of increased tone in CP. However, evidence is based largely on short term outcome and is often related to impairment level (restriction of body functions and structures) rather than measures of activity and participation as defined in the WHO's International Classification of Functioning, Disability and Health (ICF). Current research highlights that evaluation of adaptive skills (i.e. activities and participation) and quality of life are essential to assess outcome and target intervention that is meaningful to children and young people (CYP) with CP and their families. Experience in an established tertiary referral motor disorder service suggests that repeated BoNT-A injections can be beneficial for ambulant CYP with CP (Gross Motor Function Classification System (GMFCS I-III)) with careful patient selection, goal setting and evaluation of response. However, there remain many unanswered questions regarding BoNT-A's impact on activity ,participation and quality of life, together with uncertainty about the duration of response and possible adverse effects both in the short and long-term. This study aims to determine the factors associated with a response to Botulinum Toxin A injections in CYP with CP in terms of body structures and function, activity, participation and quality of life and investigate how these changes in outcome relate over time. Research questions What are the factors (i.e. age, GMFCS level, number of previous treatments) associated with change in impairment activity, participation and quality of life in ambulant CYP with CP at 6 weeks, 6 months and up to 12 months following lower limb BoNT-A treatment. How do any observed changes in clinical and patient reported outcome measures relate over time? Do standardised clinical and patient reported outcome measures relate to CYP and carer perceptions of response? Plan of investigation A sample size of 90 CYP (30 in each GMFCS levels I-III).will be recruited from the BoNT-A clinic at a tertiary motor disorders service Data Collection will take place for all participants recruited using repeated standardised clinical and patient reported outcome measures. Primary outcomes will be the 'Quality Function Measure' and goal scores as measured by Canadian Occupational Performance Measure with a range of secondary outcomes across the domains of the ICF and a quality of life measure. Assessments will be performed pre-injection, 6 weeks, 6 months and up to 12 months post injection. A subgroup of CYP and their carers (representative of GMFCS levels I-III) will participate in a qualitative component exploring their experience of BoNT-A. Descriptive analysis of the prospective study will provide information on baseline characteristics of impairment, activity, participation and quality of life. Use of multilevel models will be used to investigate change post BoNT-A use. Summary of Potential Benefits Identifying patterns of response to BoNT-A in key aspects of health across the ICF, including activity and participation, not just at impairment level will provide clinicians and families with more meaningful information to inform future treatment planning and optimise the use of BoNT-A. This study will provide information about the appropriateness of outcome measures used as well as their acceptability to CYP. Nationally, there is a drive to optimise the use of BoNT-A in CYP with CP; we anticipate that the results of this study could go on to inform a larger multicentre trial with a view to developing a robust treatment algorithm to encourage optimal use of BoNT-A injections in this cohort of patients.

Lay abstract: Some children and young people (CYP) with cerebral palsy (CP) have difficulty moving and taking part in activities because of tightness (spasticity) in their muscles. Botulinum Toxin A is a drug (often known as botox' or toxin') that can be injected into muscles to reduce tightness and make movement easier. The effect of toxin is temporary, lasting a few months, which means injections need to be repeated. The time for this varies between 4 - 12 months and in some cases longer. What we do not know yet is whether reducing the tightness in the muscles actually makes life easier for CYP with CP in terms of how much they can do (activity), how much they can join in at home, school and in the community (participation) and how long any improvements last. Also, whether what we measure as clinicians is picking up the important things that matter to CYP with CP and their families. NICE have recommended research on the topic because it is important to the NHS to inform decisions that clinicians and families have to make about the use of toxin. Clinicians and families have also identified this issue as a priority for research. This research will help answer this important uncertainty about treatment. The goal of this study is to learn about factors that affect a positive response to toxin injections for CYP with CP with an ability to walk. The questions the study wants to answer are: Does a change in stiffness, pain etc. (known as impairment) following Botulinum Toxin injections Make a difference to how a CYP can function (i.e their ability to carry out or participate in everyday life)? Influence quality of life? Are these changes dependent on the severity of the child's CP, their age at the time of injection or how many injections they have had? How long do the effects of toxin last and are there any side effects? Are clinicians measuring what is important to CYP with CP and their families and do these measurements match CYP's and parents' views of change? What do CYP and parents think about the tests that are used? I will ask CYP and their parents coming to our clinic to carry out repeated assessments at up to 4 times over 12 months (as per usual clinic procedure). Often clinic assessments focus on a patient's impairment (tightness). This study will look at a number of important areas of a child's life including activity, participation and quality of life. This will involve a clinical examination, the completion of a questionnaire (CYP and Parents) followed by goal setting before treatment and a review of the same goals after treatment. Some CYP and their parents will also take part in an interview, which will allow them to share views about their experience of receiving treatment and its impact on their life. I believe that the results of this local study will tell us which CYP receiving toxin do best, when, and for how long, helping families and clinicians to make decisions about treatment options. Following this study, I plan to compare the results with other Centres around the UK in a larger study. CYP with CP and their parents have been consulted in the preparation of this study and have helped with the study design. A group made up of CYP and parents has been set up and will advise throughout the project to make sure it remains relevant, ethical and appropriate to the needs of CYP with CP. The results from the study will be shared with families, professionals and other researchers through publications, presentations and use of social media such as closed facebook pages and interactive websites of professional and patient groups.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL