Title: What is the clinical effectiveness of hydrotherapy in maintaining physical function in people with Duchenne muscular dystrophy?
Funder: Department of Health (England)

Abstract: DESIGN: Parallel group randomised pilot trial with nested qualitative research.SETTING: Four paediatric neuromuscular units with two in reserve.POPULATION: Muscle biopsy report showing dystrophin deficiency compatible with DMD and/or a report showing the DMD gene to have a pathogenic deletion duplication or point mutation; Age 7-16 yrs; Established on glucocorticoid corticosteroids (treated with prednisolone or deflazacort for >/= 6m with no major change in drug dosage or frequency for at least 3m before the initial assessment); North Star Ambulatory Assessment (NSAA) = 8 up to 34; and able to complete 10 metre walk test with no walking aids or assistance. Exclude those: with >20% variation between baseline screens four weeks apart; unable to commit to the programme of twice weekly hydrotherapy for 6 months; contraindications to hydrotherapy.INTERVENTIONS: Participants will be allocated on a ratio of 1:1 using simple randomisation with permuted blinded block size to: (1) optimised land-based exercises (as defined by local community physiotherapy services and recorded by trial team) (n=20); or (2) The same plus hydrotherapy (30 min twice weekly for 6 months: active assisted and/or passive stretching regime; simulated or real functional activities; sub-maximal exercise) (n=20). To increase applicability and feasibility pragmatic trials may allow for intervention delivery to vary between participants practitioners or study sites and should compare new interventions to usual care (Zwarenstein BMJ 2008;337:a2390). In routine practice programmes of land-based exercises are devised taught and supervised by community physiotherapists carried out by parents carers or support staff in school. The expectation is that such programmes will adhere to DMD Standards of Care (Bushby Lancet Neurol. 2010 Feb; 9(2):177-189) including an active assisted and/or passive stretching regime undertaken a minimum of 4-6 times per week and general exercise prescription encouraging participation in regular sub-maximal age-appropriate activity. Whilst it is infeasible to enforce standardisation of land-based exercises we will record the details of each participant’s exercise programme. The final details of the hydrotherapy programme and optimal land based exercises were agreed at a consensus meeting in March 2013 and subsequent email correspondence involving patients carers physiotherapists and hydrotherapists to ensure costs to the patient and the NHS are balanced with optimal practice. The intervention has been manualised. The hydrotherapy intervention will be delivered by a suitably qualified physiotherapist who has experience in both aquatic therapy and the management of DMD. The physiotherapist will work in or have close working links with a tertiary paediatric neuromuscular centre.FEASIBILITY OUTCOMES:1. Feasibility of recruitment to main trial (recruitment of 40 participants in 6m from 4 centres with 2 in reserve (primary outcome); 2. Decision on primary endpoint for main trial (current estimate suggests 80% power two-sided with n=610 to detect 5% [18m] difference in 6 min walk test with 10% dropout at 12m); 3. Number/characteristics of eligible patients approached for the study; 4. Reasons for refused consent; 5. Participant attrition rate; 6. Reasons for attrition; 7. Participant views on acceptability of research procedures and intervention; 8. Number of missing values/incomplete cases; 9. Feasibility of recruiting participating centres; 10. Intervention fidelity; 11. Therapist views on intervention/research protocol acceptability/perceived contamination of control arm.CLINICAL OUTCOMES: The following will be assessed during routine clinical visits at baseline and 6 months (* indicates routine assessment): 1. Six-minute walk test; 2. North Star Ambulatory Assessment* (measures of functional exercise capacity); 3. Forced Vital Capacity (FVC)*; 4. Child Health Utility 9D Index (health state utility for economic evaluation); 5. ACTIVLIM (measure of independence and activity); 6. CarerQoL (carer burden); 7. Health and social care resource-use questionnaire (cost data for economic evaluation).The following safety outcomes will be assessed after each hydrotherapy session:1. Pain (visual analogue scale)2. Urine dipstick (myoglobin)3. Childrens OMNI Scale of Perceived ExertionSAMPLE SIZE: This study is an external pilot trial intended to explore the feasibility of conducting a future definitive trial. Its sample size is based on the need to estimate study parameters within a reasonable degree of precision rather than on hypothesis testing. Assuming a dropout rate at six months of 20% we will need to consent and randomise 40 participants (20 per group). The study will be rolled out at four centres with access to hydrotherapy suites (Sheffield Great Ormond Street Hospital Leeds and Birmingham) with two centres in reserve. All centres have identified a sufficient pool of eligible patients.ANALYSIS: We will present descriptive statistics for feasibility and clinical outcomes (significance testing will not be undertaken). Sample sizes calculations will be produced using a range of outcome measures and assumptions to determine whether a clinically meaningful trial can be conducted within a satisfactory timescale and cost envelope using UK centres alone. We will assess the feasibility of collecting data for the economic evaluation. Expected Value of Sampling Information will be performed on health economic results. Views of participants carers and therapists on the acceptability of the research protocol and the intervention will be analysed using the NCSR Framework approach using the Normalization Process Model which enables analysis of the conditions necessary to deliver complex interventions.TIMETABLE: We propose a 26 month project between 2014 and 2016. This incorporates: 8 months set-up; 6 months recruitment; 6 months follow-up; 6 months close-out analysis and write-up. The recruitment window is based on: (1) an expected staggered start for the six centres; (2) the known availability of eligible participants at each of the six centres (no centre has fewer than 10); and (3) allowing for recruitment at the routine (six-monthly) clinic visit which will fall within this window.


Research activity codes: 6.7 PHYSICAL;6.8 COMPLEMENTARY
Health categories: MUSCULOSKELETAL