A randomised controlled feasibility study investigating surface neuromuscular STIMulation as an exercise therapy versus usual care in people with multiple sclerosis to help improve lower limb strength, walking and fatigue (STIM-MS)

Research question Is it feasible to conduct a randomised controlled trial with parallel economic evaluation of the effectiveness and cost effectiveness of surface neuromuscular electrical stimulation (SNMES) added to usual care for improving walking, muscle strength, fatigue, quality of life and muscle spasms in people with multiple sclerosis (pwMS)?

Background Exercises can be effective for managing MS but most pwMS cannot engage at the intensity required to keep their legs strong enough for walking.

In addition to financial and access barriers, fatigue, pain, spasms, low mood, depression, cognition, heat sensitivity, restricted movement and spasticity further limit engagement. SNMES has been used to make the muscles of pwMS contract in a similar way to resistance training.

SNMES could help overcome existing barriers to engagement enabling people to achieve the exercise intensity needed for preserving or improving muscle function, potentially maintaining walking ability for longer and preventing a downward spiral of reduced exercise tolerance, walking ability, physical activity weakness, and fatigue.

Before we can run a definitive trial of SNMES, we need to undertake a feasibility study to gather information about aspects of study processes and key parameters for which there is uncertainty.

Objectives To determine whether a future definitive trial is feasible by: Estimating screening, recruitment and attrition rates.

Collecting data on candidate outcome measures to determine the primary outcome for the future trial and enable sample size calculations based on this. Determining intervention acceptability. Evaluating the feasibility and acceptability of health economics measures.

Qualitatively exploring via interviews participants , carers and clinicians views and experiences of study processes and the intervention.

Methods Randomised controlled feasibility study comparing SNMES plus usual care versus usual care only with a nested qualitative study.

Intervention group Participants will be given SNMES equipment to use at home on their bilateral thigh and shank muscles over 12-weeks, working towards 3 x 30 min sessions/week (45 contractions per muscle group). Control group Participants will continue to receive their usual care only.

Outcome measures (baseline, 12-weeks and 6-months follow-up post randomisation) Muscle function, (Timed-up-and-go), exercise tolerance (2-minute walk test), spasms (PSFS), disease-specific quality of life (MSIS-29) and fatigue (MFIS-5) measures will be included. Analysis Descriptive statistics will be used to summarise data in respect to objectives.

Progression criteria and amendments will be evaluated using the a priori traffic-light system. Qualitative data will be analysed using reflexive thematic analysis.

Timelines for delivery Total study duration is 30-months with 4-months set-up and site training, 15-months recruitment and final follow-up 6-months post-randomisation of the last participant. Months 24-30 will include data entry, analysis and study write-up.

Anticipated Impact and Dissemination Dissemination strategy and materials will be developed with the PPI group to ensure accessibility.

Findings will be shared via charities, clinical networks, social media and newsletters as well as academic publications and conference presentations. We will leverage public engagement resources and events available through co-applicants' institutions.

Findings will inform the development of a future definitive trial of SNMES, potentially providing an evidence- and home-based treatment for pwMS and limited mobility.