Title: Strengthening Mental Abilities with Relational Training (SMART) in Multiple Sclerosis (MS): A feasibility trial
Funder: Department of Health and Social Care

Abstract: Background: Multiple Sclerosis (MS) is a chronic condition of the central nervous system; around 1 in 600 people in the UK have MS(1). Many people with MS (70%) have cognitive difficulties(2), which they experience as distressing and disabling(3), and there is currently a lack of treatment options to improve these difficulties(4). SMART (Strengthening Mental Abilities with Relational Training) &ndash; a theory-based online cognitive training programme, which has been shown to improve general cognitive abilities(5) &ndash; has not been tested with people who have MS. Aims: To conduct a feasibility study to inform development of a definitive trial of SMART for improving cognitive functioning in people with MS. We will: 1. Adapt the SMART intervention for people with MS And assess: 2. Acceptability to participants of the intervention, delivery format, inclusion/exclusion criteria, baseline and outcome measures, randomisation protocol, and study procedures 3. The framework for a cost-effectiveness analysis alongside a definitive trial 4. Participant recruitment and retention rates 5. Sample-size needed for fully powered trial 6. Signal of efficacy Plan: The standard SMART intervention will be tailored for people with MS through cognitive interviewing and usability testing addressing Aim 1. Participants will be identified from MS patients in our NIHR-funded NeuroMS study (www.neuroms.org) who have expressed interest in further research. To address Aims 2-6, we will recruit 60 adults with MS who are experiencing cognitive difficulties, identified from MS clinics. Participants will complete baseline assessments of their cognitive abilities and answer questionnaires about their cognitive difficulties, personal priorities, mood, fatigue, self-efficacy, quality of life, and healthcare services used. Assessments will be administered by a researcher, face-to-face or remotely. Participants will be randomly allocated to one of three arms (20 per group): Group 1: Receives SMART intervention online &ndash; plus usual care (MS Nurse support). SMART intervention involves completing a series of logic problems, which are designed to train skills that scaffold complex cognition. Group 2: Receives usual care alone. Group 3: Receives a control intervention online &ndash; plus usual care. The control ( sham ) training is Sudoku &ndash; selected based on popular conceptions that it broadly improves cognitive functions(6), coupled with little evidence supporting this notion(7). Baseline measures will be re-administered at three- and six-months post-randomisation. Researchers and patient-partners (people with personal experience of MS, who will act as co-researchers) will also interview 30 participants about their experience of the study and treatment. All qualitative data will be transcribed and thematically analysed in terms of a priori feasibility aims. Quantitative data will enable sample-size calculation for a definitive study and determine signal of efficacy. Potential benefits to patients/NHS: This study will enable development of a Phase III RCT evaluating the effectiveness of SMART intervention for addressing cognitive difficulties in people with MS. If effective, patients may experience improved cognitive functioning, greater confidence performing daily activities, and better quality of life &ndash; thereby, reducing reliance on health services, and ameliorating NHS pressures. If effective, this low resource, remotely deliverable intervention would improve access to cognitive rehabilitation at low cost to the NHS.

Lay abstract: Multiple Sclerosis (MS) is a lifelong illness that affects the brain and spinal cord. Around 1 in 600 people in the UK have MS. Many people with MS (70%) have problems with thinking skills. These problems cause them distress and disability. There is a need for treatments to improve these problems. SMART &ndash; an online brain training treatment &ndash; can boost thinking skills, but has not been tested with people with MS. Aims 1. Adapt the SMART treatment to make it fit for people with MS. 2. Assess whether we can do a large study to test whether SMART treatment improves thinking skills in people with MS Methods Patients aged 18-89, seen in MS clinics, will be invited to take part and sent study details. Those who fit the study will be asked to do some tests of thinking skills and fill in some forms about their problems with thinking, mood, and health. Patients will then be put into three groups by chance (20 in each group): Group 1: Receives online SMART treatment in addition to their usual care (MS Nurse support). SMART treatment involves doing a series of puzzles. These puzzles are designed to train key skills that support thinking and new learning. Group 2: Receives usual care alone. Group 3: Receives a control online treatment plus usual care. The control treatment is a puzzle activity (Sudoku). This allows us to compare SMART training to an activity that looks similar but is not designed to have the same benefits. Three and six months later, patients again complete the tests and forms that they did before treatment. Researchers and patient-partners (researchers who live with MS) will also interview 30 patients about how they found the study and treatment received. Patient and Public Involvement (PPI) The study was designed with our PPI group. One member of our group co-wrote this summary. Members will be trained to carry out feedback interviews as patient-partners, advise on how we recruit patients, and present the findings at PPI events. Results will be published in health science journals, shown at meetings, and shared through newsletters and websites of MS charities (e.g., MS Society). The wider public will be told about the study through our public websites and press offices. Extra work on dementia and neurodegenerative disease Examining the feasibility of trialling the theory-based computerised cognitive training intervention &ndash; the SMART programme &ndash; for people with MCI. This will include: Convening a Patient and Professional Involvement group representing MCI patients, carers, and practitioners to get input on trial procedures. Recruiting patients through memory assessment service clinics in Nottinghamshire Healthcare NHS Foundation Trust or the Join Dementia Research register. Recruitment targets will be 20 patients and an unequal randomisation of 2:1:1 will be used (10 patients receive SMART, 5 patients receive active control training, and 5 patients receive usual care).

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: NEUROLOGICAL