Efficacy and mechanism of sub-sensory sacral (optimised) neuromodulation in adults with faecal incontinence: study protocol for a randomised controlled trial.

BACKGROUND: Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. METHODS/DESIGN: The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). DISCUSSION: This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN98760715 . Registered on 15 September 2017.