1. SuMS SUM S SuMS S tanding U p in M ultiple S clerosis SUMSstudy@plymouth.ac.ukstudy@plymouth.ac.uk South West Contacts: Dr Jenny Freeman  01752 588835 Esther Fox  01752 587599 East Anglia Contacts : Dr Wendy Hendrie  07826161868 /01603 488561 Steve Hooley  01603 488561

2. A multi-centre randomised controlled trial to assess the effectiveness and cost effectiveness of a home-based self-management standing frame programme plus usual care versus usual care in people with progressive MS who have severely impaired balance and mobility. Investigators: J Freeman, W Hendrie, L Jarrett, A Barton, S Creanor, A Hawton, J Marsden, J Zajicek SuMS

3. Study background and rationale 66% of PwMS move to a progressive phase in 8 years 50% of PwMS are unable to walk unaided in 15 years 25% will become dependent on a wheelchair Typically, people with such limited mobility are excluded from clinical trials, which tend to focus on the relapse-remitting stage of MS

4. Study background and rationale Mobility: Is a major concern for pwMS and health professionals. Is consistently ranked by pwMS as their highest priority 1 and most important yet most challenging daily function 2. Spans much more than walking 3, including activities necessary for daily functioning: the ability to stand, safely transfer from wheelchair to toilet or to bed, and to move about in bed. Correlates negatively with employment status, earnings and quality of life 4.

5. Study background and rationale 25% of PwMS spend much of their day sitting ↓ 2 ○ complications Physical problems Psychosocial problems ↓ quality of life 5 Significant economic costs: ~ 15% of pwMS develop pressure sores (costs of a single sore range from £1,064 (grade 1) to £24,214 (grade 4) 6. Average cost per wheelchair dependent patient is 4–5 times > ambulatory patient 7. Significant ↑ in emergency hospital admissions in people with progressive neurological disability, including MS. Weakness, pain, spasms, muscle / joint stiffness, constipation, chest infections Depression Lower self esteem Self identity issues

6. Study background and rationale ↑ physical activity beneficial …. but difficult with severe disability On-going physiotherapy rarely possible (resource restrictions) Typical bias of group-based ex. programmes towards ambulant individuals Effective self-mg’t strategies are needed but challenging, esp. with severe disability Regular supported standing using standing frames is one potential option Long-term Neurological Conditions Research Initiative recommend “provide people with equipment to help them to self-manage and be independent” and commissioners to “develop preventative services that support people to self-manage”.

7. Supportive research Hendrie et al 2014 8 Mixed-methods approach: 9 in-depth single case studies 4 regular standing over 1 year, 30 minutes/ 3x weekly Objective improvements in strength, ADL, spasms (but not pain, bowel frequency) 27 in-depth interviews revealed how the programme reinstated a sense of belonging & optimism by restoring important life roles & feelings of normality It enabled them to: “reconnect with their body”, “regain lost skills”, and gain a sense of “being in control”, “to be the same person (they were)”, “feel so much more alive” ……realise “I’m human after all” Marsden, Ofori and Freeman 2013 9 Lab-based MS studies: duration & magnitude of force required to ↓ stiffness in hypertonic LL muscles only achieved in supported standing position with ↑ disability

8. Supportive research Baker et al 2007 10 Pilot cross-over RCT: home based standing 30 minutes daily 3 weeks vs ex. programme Participants: n = 6, > 7.0 EDSS, 2 ○ progressive MS Outcomes: Spasticity, spasms, range of motion LL joints (0, 3, 6 weeks) Results: sig. in standing group ↑ hip and ankle ROM, trend ↓ spasticity and spasms Newman et al 2012 11 Systematic review investigating effectiveness of supported standing in neurological conditions highlighted that more robust evidence is required. 17 RCT’s ….2 were high quality…. only one (Baker 2007) in MS. Discussions with 10 Specialist MS physiotherapists indicated that ~ 90% of severely impaired people are suitable candidates; many offered a standing frame are keen to try it

9. Aims of SUMS study Primary aim to assess the clinical and cost effectiveness of the home-based standing frame programme plus usual care versus usual care Secondary aim to qualitatively explore the impact of this programme from the perspective of the person with MS and their carer

10. Objectives of SUMS study 1. Assess clinical effectiveness in improving motor function (primary outcome) and quality of life. 2. Assess clinical effectiveness in improving balance, muscle strength, joint and muscle range, painful spasms, respiratory, bladder and bowel function, number of falls (secondary outcomes). 3. Establish cost effectiveness 4. Explore the subjective experience of using a standing frame within the home (pwMS and carer perspective).

11. SUMS Trial Design Pragmatic multi-centre RCT with blinded outcome assessment and full economic evaluation. 3 year study 140 people with progressive MS Standing programme over 20 weeks plus 16 week follow up Intervention by NHS physio’s (web-site training materials, DVD, information booklets, telephone reviews etc provided) Blinded assessments by research therapist at local centres: 0, 20, 36 weeks Audio diaries 20 people throughout study

12. Study sites Northern Devon Trust Plymouth Community Health Royal Devon and Exeter NHS Trust Peninsula Community Health Torbay and Southern Devon Health and Care Trust Norfolk Community Health and Care Trust Suffolk Community Health and Care Trust

13. Inclusion Criteria People with confirmed primary or secondary progressive MS aged >18 years willing and able to consent EDSS 6.5-8.0 i.e. “require bilateral assistance to walk 20 metres or less” to those “restricted to bed or wheelchair” able to accommodate a standing frame within their home able to get into a standing frame with assistance from a carer agreement of carer/ spouse to provide assistance able to travel to local assessment centres for outcomes assessment

14. Exclusion Criteria recent changes in disease modifying therapies relapsed / received steroid treatment within the last month currently, or during the past 6 months have undertaken a regular standing frame programme (>x1/week) history of osteoporotic-related fractures co-morbidities which contraindicate standing in the frame (e.g. foot ulceration, uncontrolled epilepsy) co-morbidities which likely to impact on the trial (e.g. chronic jaundice, heart disease, age related multiple co-morbidities) currently participating in another clinical trial (rehabilitation or pharmacological)

15. Study Resources SUMS Study Protocol (Version 2.0, 27.4.15) Flowchart of Participant Pathway through the study Access to SUMS Study Web-site www.plymouth.ac.uk/research/sumswww.plymouth.ac.uk/research/sums - SUMS Study Overview - SUMS study information sheets -How to Use the Standing Frame Information Booklet -Videos of How to use and exercise in the Standing Frame -Relevant articles -Regular updates on the progress of the study, dissemination etc.

16. Study Resources Standard Operating Procedure Instructions: SUMS SOP B01 Adverse Event Reporting (with SAE Form and Withdrawal Flowchart and Withdrawal of Participant Form) SUMS SOP C02 Screening Procedure SUMS SOP CO5 NHS Treating Physiotherapist Intervention Procedure SUMS SOP D02 Protocol Deviations SUMS SOP D03 Fidelity Checklist SUMS SOP D06 Goal Setting / Telephone Review

17. Study Resources To give to patient at first visit: Standing Information Booklet DVD – Using the Frame and Exercising in the Frame Standing Daily Diaries For therapist to complete (one copy for notes, one for SUMS research team) Fidelity Check list (i.e. your intervention in a checklist format for the first and second visit) Telephone Review Documentation (6 telephone review forms)

18. Many thanks for your help with this study – please do not hesitate to contact us if you have any queries whatsoever. If you know of any other people with MS who may be interested in participating in this study, please do let us know. SUMSstudy@plymouth.ac.ukstudy@plymouth.ac.uk

19. Scientific References 1. Sutliff MH. Contribution of impaired mobility to patient burden in multiple sclerosis. Current Medical Research Opinion 2010; 26: 109. 2. Heesen C et al. Patient perception of bodily functions in multiple sclerosis: Gait and visual function are the most valuable. Multiple Sclerosis 2008; 14:998–991. 3. National Institute of Clinical Excellence. Multiple Sclerosis: national clinical guidelines for the diagnosis and management in primary and secondary care, 2003 4. McCrone P et al. Multiple sclerosis in the UK: service use, costs, quality of life and disability. Pharmaco Economic 2008; 26: 847–860 5. Jones S et al. The burden of multiple sclerosis: A community health survey. Health Quality of Life Outcomes 2008; 6:1 doi:10.1186/1477- 7525-6-1 6. Royal College of Physicians The national audit of services for people with multiple sclerosis 2011. Royal College of Physicians, London. 7. Kobelt G et al. Costs and quality of life of multiple sclerosis in the United Kingdom. European Journal of Health Economics 2006; 7: S96-104 8. Hendrie W et al. A pilot mixed methods investigation of the use of Oswestry standing frames in the homes of nine people with severe multiple sclerosis. Disability and Rehabilitation, 2014. DOI: 10.3109/09638288.2014.957790 9. Marsden J et al. Factors influencing the applied torque during manually applied plantarflexor stretches in people with Multiple Sclerosis (Abstract). MS Frontiers Conference, London, 2013. 10. Baker K et al. Therapeutic standing for people with multiple sclerosis: Efficacy and feasibility. International Journal of Therapy and Rehabilitation, 2007; 14 (3): 104-109. 11. Newman M & Barker K. The effect of supported standing in adults with upper motor neurone disorders: a systematic review. Clinical Rehabilitation. 2012; 26(12): 1059- 1077