Title: A programme to develop and evaluate a complex intervention to achieve a high calorie diet for people with Amyotrophic Lateral Sclerosis (HighCALS)
Funder: Department of Health and Social Care

Abstract: Aims The proposed programme aims to develop and test a complex intervention (HighCALS) to enhance the nutritional management of people living with ALS, leading to improvements in survival and quality of life. Underpinning HighCALS is a programme of work to understand the current national service models, the beliefs of stakeholders and the development of behaviour change strategies to support and improve nutritional interventions. Background Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a devastating neurodegenerative disorder. People with ALS (pwALS) experience a progressive weakness of limb muscles, loss of speech, chewing and swallowing, eventually succumbing to the consequences of respiratory failure due to respiratory muscle weakness. There is no cure for ALS. Malnutrition and weight loss are well recognised poor prognostic factors in ALS. In pwALS with weight loss of 5% or more there is a two-fold increase in risk of death, compared to those who have lost less than 5% of their usual pre-morbid weight. Current guidelines are not evidence-based and do not include any guidance on nutritional management with regard to assessment of nutritional status, total daily energy expenditure calculations, appropriate dietary intake or oral nutritional supplementation. Surveys indicate a lack of knowledge in healthcare professions regarding the nutritional management of ALS. The poor evidence base explains the poor nutritional outcomes observed. The weight loss in pwALS is compounded by hypermetabolism with resting energy expenditure being, on average, 20% higher than in healthy individuals. Encouragingly, correction of the energy deficit with a high calorie diet extended life by 20% in an ALS mouse model. Moreover, in pwALS a small pilot study indicated a potential survival advantage and tolerability of a high calorie diet. There is a need to confirm the potential of a high calorie diet to influence the disease course in ALS. Research plan WP1: Exploring current services (Months 1-8) 1.1 We will conduct a mapping review on the structure and activities of the nutritional management services for pwALS. 1.2 We will conduct consultation groups with stakeholders involved in the nutritional management of pwALS to gain further insight into the structure of nutritional management services and current nutritional practice. 1.3 Informed by the mapping review and consultation group findings, we will develop two national surveys. The first will be sent to commissioners, lead clinicians for ALS and dietetic managers. The second survey will be distributed nationally to ALS MDT members. 1.4 Findings from WP1 will inform the workshops with healthcare professionals in WP2 exploring barriers and enablers of nutritional interventions. They will also be used in the development of the HighCALS intervention (WP3), specifically related to ensuring that the intervention can take place within existing services and be implemented into clinical practice. WP2: Understanding barriers and enablers (Months 1-12) 2.1 We will conduct a systematic review on factors (e.g. beliefs, knowledge) associated with nutritional behaviours (e.g. compliance with oral nutritional supplements) to achieve a high calorie diet in ALS. 2.2. We will conduct a systematic review on interventions to promote nutritional behaviours to achieve a high calorie diet in ALS. 2.3 We will conduct interviews with patients and carers to explore their beliefs about the barriers and enablers of nutritional interventions in ALS. 2.4 We will conduct focus groups with MDT members to explore their beliefs about the barriers and enablers of nutritional interventions. WP3: HighCALS intervention development (Months 1-25) 3.1 We will synthesise and link the key modifiable factors associated with nutritional behaviours to achieve a high calorie diet in ALS and the key features of interventions (e.g. behaviour change techniques) to promote these behaviours. 3.2 We will develop materials and strategies, including an online portal, for MDT members and pwALS/carers as part of the HighCALS intervention. 3.3 We will conduct interviews with patients, carers and MDT members to assess the acceptability and usability of the proposed materials and strategies. 3.4 We will develop a training session for MDT members to deliver the HighCALS intervention. WP4: Cost effectiveness study (Months 24-69) We will conduct a multi-centre RCT to assess the effectiveness and cost-effectiveness of an early high calorie diet on functional outcomes in ALS, comprising two treatment arms: 1) Standard care, 2) Standard care with additional active management using the HighCALS complex intervention to achieve a high calorie diet. A cost-utility analysis will be undertaken using the resource use, EQ-5D-3L and mortality data from the trial; comparing active management for achieving high calorie diet with standard care. A process evaluation will also be incorporated. PPI The research team established the Sheffield Motor Neuron Disorders Research Advisory Group (SMNDRAG) public and patient group in 2008. The group has worked collaboratively in shaping this proposal and individuals from SMNDRAG will be supported to contribute to project delivery.

Lay abstract: Aim To ensure people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), receive the optimal diet at the most appropriate time in the most cost effective manner. We believe addressing this potentially simple issue could have a dramatic impact on survival, function and quality of life for the 6000 people with ALS (pwALS) in the UK. Background There is currently no effective treatment for ALS. It causes progressive paralysis and then death. Research suggests pwALS have an increased calorie requirement and those that eat a high calorie diet may have improved survival. However, calorie consumption in many pwALS is much lower than needed. The reasons for this need further exploration but include: (i) lack of official guidance on how best to manage weight and nutrition in pwALS, (ii) poor knowledge of the calorie requirements of people with ALS by healthcare professionals, pwALS and carers, and (iii) the physical, social and psychological impacts of the disease. Design We will: Explore current practices relating to nutritional care of ALS patients. Use surveys, workshops and interviews to understand the practical, social and psychological barriers and enablers from the point of view of patients, carers, healthcare professionals, commissioners and services managers. Combine our findings to develop ALS specific materials (the HighCALS intervention) to increase the effective use of nutritional interventions, drawing upon behaviour change techniques. Make recommendations for service design, skill mix of supporting health professionals and education. Undertake a trial with 304 pwALS comparing a high calorie diet (delivered using the HighCALS intervention) with current practice, to see if this new approach can improve survival and quality of life. PPI The Sheffield Motor Neuron Disorders Research Advisory Group identified a problem with the lack of a consistent message for pwALS, regarding weight and nutrition from healthcare professionals. They expressed frustration at the lack of information available about the importance of preventing weight loss or how to manage their diet as their condition progresses. Their feedback during the development stages, resulted in a redesign to ensure behavioural and psychosocial issues regarding nutrition were incorporated. PwALS will be involved in all stages of the research to include: Membership of the project management group, steering committee and work package groups Reviewing the content and accessibility of patient information Contributing to the development of the nutritional interventions Supporting the development of outputs of the research findings Dissemination Planned outputs in the ALS Journal, MNDA website, and dietetic journals will increase awareness of healthcare professionals, patients and carers of the benefits of managing the nutritional intake of patients with ALS. Reports distilling the findings will be sent to NHS commissioners, policy makers and NICE.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL