Journal Article

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

Dudding, Tom C., O’Connell, P. Ronan, Hooper, Richard L., Scott, S. Mark, Jones, James F. X., Knowles, Charles H., Vollebregt, Paul F., Norton, Christine, McAlees, Eleanor, Hamdy, Shaheen, Furlong, Paul L., Stevens, Natasha, Emmanuel, Anton V.

2018

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Adult / Adults / Aged / Analysis / Behavior modification / Biomedicine / Care and treatment / Clinical trials / Costs / Cross-Over Studies / Defecation / Double-Blind Method / Electric stimulation therapy / Evoked potential / Faecal incontinence / FDA approval / Fecal incontinence / Fecal Incontinence - diagnosis / Fecal Incontinence - physiopathology / Fecal Incontinence - therapy / Female / Germany / Health aspects / Health Sciences / Humans / Hypotheses / Incontinence / Ireland / Lumbosacral Plexus / Magneticoencepholograpy / Male / Medicine / Medicine & Public Health / Middle Aged / Multicenter Studies as Topic / Neurophysiology / Older people / Pathophysiology / Patients / Randomised controlled trial / Randomized Controlled Trials as Topic / Recovery of Function / Regulatory approval / Sacral nerve stimulation / Sacral neuromodulation / Statistics for Life Sciences / Study Protocol / Time Factors / Transcutaneous Electric Nerve Stimulation - methods / Treatment Outcome / United Kingdom / Young Adult