The Efficacy of Peroneal Nerve Functional Electrical STimulation (FES) for the Reduction of Bradykinesia in Parkinson’s DiSease: An Assessor Blinded Randomised Controlled Trial (STEPS II).

Research Question Does Functional Electrical Stimulation (FES) delivered to the common peroneal nerve of people with Parkinson’s Disease (pwPD), in addition to usual care, reduce bradykinesia in comparison with usual care alone and if so, what are the mechanisms of action? Background Difficulty in walking is a common problem for pwPD and is characterised by bradykinesia, hypokinesia, festination, akinesia and reduced balance. Case series data indicates that bradykinesia may be reduced by FES, indicated by increased walking speed (WS). This may persist for hours or days after the last use of FES. The hypothesised mechanism of action is that FES reduces the variability stepping and this allows the sensorimotor system to adapt inter-limb coordination and anticipatory postural adjustments (APAs), leading to improved WS. Aims and Objectives Primary aim; to test the hypothesis that daily use of FES delivered to the common peroneal nerve in addition to usual care reduces bradykinesia, in comparison to usual care alone, demonstrated by a clinically meaningful between-group difference in WS (=0.13ms-1). Secondary aims; to assess the carryover effect of FES and to produce the first robust estimates for the effect on hypokinesia, akinesia, falls and balance, activities of daily living and quality of life. Mechanisms of action will be explored by assessing short-term changes in inter-limb coordination, dynamic balance and limb bradykinesia and assess their relative contributions to improved WS. Study design A multi-centre, 2-arm, parallel, assessor-blinded, superiority, individually randomised controlled trial comparing FES with usual care to usual care alone. The primary end-point is at week 18. FES is then withdrawn and further assessments made at week 22 to study the potential carryover. 234 pwPD from 7 sites will be recruited in this 43 month study. Outcome measures The primary outcome; 10m WS (FES off). Secondary outcome measures are step length, Unified Parkinson’s Disease Rating Scale parts 2-4, Parkinson’s Disease Questionnaire PDQ39, New Freezing of Gait questionnaire, Mini Balance Evaluation Systems Test, falls diary, Falls Efficacy Scale International questionnaire, StepWatch activity monitor and EuroQol 5D-5L, collected at weeks 0,2,6,18&22 by a blinded assessor. Inertial motion sensors will assess limb bradykinesia, inter-limb coordination and APAs while stepping and walking. Leg muscle strength will be assessed by dynamometry. In the intervention group, the clinician will record WS, step length, Borg rate of perceived effort and the timed up and go test at weeks 1,6&18 (FES on). The experience of participants using FES and their carers will be investigated using qualitative telephone or video-call interviews. Analysis Trial reporting will follow CONSORT guidelines. Primary analysis (intention-to-treat) of WS will use a longitudinal linear regression mixed effects model, adjusting for recruitment site and baseline WS, using multiple imputation to handle missing data. The FES treatment effect at 18 weeks will be estimated from this model. Causal mediation analysis will be performed to assess potential short-term mechanistic pathways on change in WS at 6&18 weeks. Anticipated impact and delivery FES may significantly improve the mobility of pwPD, reducing disease impact, increasing quality of life and reducing dependency. The study results may update NICE guidelines for FES and PD, and knowledge on the mechanisms of action of FES.