Title: Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis (CRAMMS)
Funder: Department of Health and Social Care

Abstract: Design: Randomised control trial comparing cognitive rehabilitation and usual care with usual care alone Setting: Hospital outpatients and community participants Population: People with multiple sclerosis who report cognitive problems in daily life and have evidence of cognitive impairment on testing Inclusion/exclusion criteria: We will include people with MS who report cognitive problems on the Multiple Sclerosis Neuropsychological Questionnaire and cognitive deficits on the Brief Repeatable Battery of Neuropsychological Tests, are aged 18 to 69 years, able to speak English and give informed consent. People with severe medical and psychiatric conditions will be excluded. Health Technology to be assessed: Cognitive rehabilitation offered to groups of up to 6 participants for 10 weekly sessions. The programme will be tailored to each patient’s cognitive status while maintaining a systematic approach to attention and memory by following a treatment manual. The intervention will include restitution strategies (internal mnemonics/attention retraining), compensation strategies (external devices, diaries), errorless learning, and ways of coping with cognitive problems. The aim will be to identify the most appropriate strategies to help people with MS overcome their difficulties, and to provide techniques to adapt according to their needs. To check the fidelity of the intervention, the content of some treatment sessions will be video recorded. Control group participants will receive their usual clinical care, which may include information on cognitive problems but not cognitive rehabilitation. Measurement of Costs and Outcomes: The primary outcome measure will be the Multiple Sclerosis Impact Scale (MSIS) Psychological Subscale (a quality of life measure) at 1 year after randomisation. Secondary outcome measures: Doors and People, and Everyday Memory Questionnaire patient and relative versions to assess attention and memory; General Health Questionnaire-30 to assess mood; Fatigue Severity Scale; Employment status; EQ-5D to determine health-related quality of life; Modified Carer Strain Index to assess the effect on carers; Cost-effectiveness will be determined from the use of clinical services and medication costs. These measures will be administered 6 and 12 months after randomisation by a researcher blind to group allocation. A sample of participants (n=32) from both groups will also be interviewed at 6 months to provide qualitative feedback. Sample size: Based on our pilot study, to detect a difference of 3 points on the MSIS Psychological subscale, with SD=9, 5% alpha, 90% power, ICC=0.1 in intervention arm only, 336 participants are required for analysis. Assuming 15% do not provide primary outcome data, we will randomise a total of 400 (216 to intervention and 184 to usual care). The main analyses will be intention-to-treat. Project timetable Months -3-0 Ethics approval 1-6 Preparation 8-31 Recruitment 14-43 Outcome assessments 16-46 Qualitative interviews and analysis 35-48 Analysis and dissemination Expertise in the team: This multidisciplinary team is led by two clinical neuropsychologists, one university and one NHS based. The co-applicants include a neurologist, occupational therapist, statistician, health economist and service user, in collaboration with a clinical trials unit. Many of the team have worked together on previous trials of cognitive rehabilitation and with people with MS.

Lay abstract: About two thirds of people with multiple sclerosis have cognitive problems. These problems include difficulties with paying attention, learning, remembering new things, and planning activities. These problems are long term: they can be distressing for the person, their families and friends, and lead to difficulties for those in education or in paid employment. Cognitive rehabilitation is a structured set of activities designed to retrain peoples’ cognitive functions. People are taught strategies to improve their attention, to reduce forgetting, and to deal with complex everyday tasks. Several small studies have suggested that cognitive rehabilitation can help people with multiple sclerosis. However, these studies were not of high enough quality or large enough to really tell us whether cognitive rehabilitation is worthwhile for people with multiple sclerosis. This study will test whether 10 weekly group cognitive rehabilitation sessions with a psychologist improves the quality of life for people with multiple sclerosis who have cognitive problems. Our preliminary work showed that this cognitive rehabilitation programme can be used within the NHS for people with multiple sclerosis. Adults with multiple sclerosis who have problems with attention and memory will be invited to take part in the study. They will be contacted through NHS hospitals, community rehabilitation services and local groups organised by the MS Society. People who would like to participate will be asked to complete a questionnaire to assess how severe their cognitive problems are. Those with substantial problems will be invited to take part. If they agree, they will see a psychologist who will do some assessments to check their cognitive abilities. They will then be ‘randomised’ (that is, allocated by chance) to have either the cognitive rehabilitation in addition to their usual care, or to their usual care alone. We will offer travel expenses, and conduct the groups in suitable venues, so that we can include those with mobility problems. Six and 12 months after joining the study, we will send participants questionnaires to complete, and a researcher will arrange to visit them at home to repeat some assessments. These questionnaires and assessments will tell us about their attention and memory, any cognitive problems in daily life, mood, fatigue, quality of life and employment status. Carers will also be asked to complete a questionnaire to assess their stress levels. We will compare the results of those who had the rehabilitation and those who did not. We will invite some participants to an interview, where they can tell us about any perceived benefits of the cognitive rehabilitation and their experience of being in the study. This information will tell us about the strengths and areas of further development of our cognitive rehabilitation programme, so that we can modify it on the basis of participant feedback, before it can be rolled out to the NHS, if found to be effective. These interviews will be done by someone who was not directly involved in doing the assessments or providing the rehabilitation. We will also determine the cost-effectiveness of providing the rehabilitation. With the consent of participants, we will record some of the treatment sessions. This, along with the treatment manual, will serve as training tools. This will enable us to train therapists to deliver the intervention as part of NHS services for people with multiple sclerosis.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;7.1 INDIVIDUAL CARE NEEDS
Health categories: MENTAL HEALTH;NEUROLOGICAL