The use of neuromuscular electrical STIMulation as a treatment for sarcopenia in people on HaemoDialysis

Research question: is a programme of neuromuscular electrical stimulation (NMES) effective in improving or reversing the condition of sarcopenia in people undergoing maintenance haemodialysis (HD)?

Background: Sarcopenia is common, associated with poor outcomes and costs the NHS approximately £2.5 billion annually. Chronic kidney disease (CKD) affects >10% of the UK population and the prevalence of sarcopenia in the HD population is highest. Currently the most effective treatment for sarcopenia is exercise but as many as 74% of HD patients are unable to participate in such programmes; an alternative is clearly needed.

NMES uses intermittent electrical stimuli to generate involuntary muscle contractions and may serve as an ‘exercise mimetic’. It is currently used in other clinical populations including intensive care and rehabilitation, and feasibility studies in CKD have shown that it is safe. However, NICE have highlighted there are a lack of long term, suitably powered and appropriately controlled randomised trials demonstrating any effect of NMES on muscle strength in the CKD population.

Aim: To test the clinical efficacy of NMES as a therapy for sarcopenia in people on maintenance HD, both in-centre and at home.

Intervention and control: The intervention will be a 3-month structured and progressive programme of NMES, 3 times per week for a 30-minutes. Control participants will receive standard care with all other dialysis care remaining the same.

Outcomes: The primary outcome will be change in muscle strength from baseline between intervention and control groups. This and other secondary outcomes will be investigated using four work packages (WPs) • WP1 will determine the optimal stimulation parameters for NMES in the HD population in an external pilot

• WP2 will measure the effect of a 3-month NMES programme on muscle strength compared with standard care for HD patients • WP3 will evaluate the cost-effectiveness of a NMES programme compared with standard care • WP4 will investigate if NMES results in neuromuscular adaptations and changes in muscle phenotype

Methods: For the external pilot (WP1), 24 participants will be recruited to determine the optimal starting protocol of NMES for WP2. This will include changes in stimulation frequency, intensity and pulse duration, the pattern of contraction and rest intervals.

WP2 will be a prospective, open-label, assessor blind, two-arm, multi-centre, randomised controlled trial of 228 sarcopenic HD patients randomised 1:1 to NMES or control. Participants will continue to be followed up for an additional 6-months to assess the sustained effect of the NMES intervention. The cost effectiveness of the intervention will be determined in WP3 by evaluating the quality adjusted life years associated with the NMES programme.

A parallel mechanistic work package (WP4) will determine the effect on neuromuscular adaptations (using intramuscular electromyography n=50) and muscle phenotype (muscle biopsies n=24).

Timelines: Months 1-6 set up and external pilot, months 6-27 recruitment to efficacy trial, month 36, last patient, last follow up visit, months 36-42 data and sample analysis.

Anticipated impact and dissemination: As well as direct impact upon patients and their relatives, this research has the capacity to lead to a direct change and adoption within UK and global practice. We will disseminate the results thorough national and international conferences and in high impact journals.