EFFECT OF SUB-SENSORY SACRAL NEUROMODULATION ON FAECAL INCONTINENCE IN ADULTS: A RANDOMISED CROSSOVER TRIAL WITH COHORT FOLLOW-UP AND MECHANISTIC SUB-STUDY

Background
Sacral neuromodulation (SNM) is considered the first-line surgical treatment in adults with refractory faecal incontinence (FI). The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear.
Trial design
Randomised, multicentre, double-blind crossover trial (2x16-week periods) of active stimulation vs sham and open-label follow-up to 58 weeks. Embedded mechanistic study using magnetoencephalography (MEG) on bidirectional functional connectivity between brain and anorectum.
Methods
Participants: adults aged 18-80 with refractory FI. Interventions: active: subsensory stimulation of a sacral nerve using a commercially available surgically implanted pulse generator; sham: identical implant but turned off. Patient-chosen sub/supra-sensory open label stimulation from week 32 to 58. Primary objectives: to determine whether: (1) sub-sensory SNM led to a reduction in FI episodes per week compared to sham; (2) clinical responses to sub-sensory SNM were biologically related to changes in evoked and induced activity between the brain and anorectum. Primary outcome: FI episodes per week based on paper bowel diary performed in the final 4 weeks of each crossover period (allowing 12 weeks washout). Randomised allocation (1:1) to arm 1 (SNM/SHAM) or 2 (SHAM/SNM). Blinding: participants, surgeons, assessors; tamper proof tape masked stimulation settings. Sample size: 80 patients required to detect 30% reduction in episodes (alpha=0.05; power 90%).
Results
Recruitment: a total of 39 patients of 220 screened and 65 pre-enrolled (arm 1: N=17; arm 2: N=22) were recruited to the crossover trial of whom only 16 (arm 1: N=9; arm 2: N=7) had complete primary outcome data. Of these, 19 completed follow-up to 58 weeks. Trial delivery was severely affected by COVID-19. 25 patients underwent MEG studies compared to 20 healthy volunteers. Primary outcome (N=16): SNM conferred a non-significant reduction in mean FI episodes per week compared to sham (-0.7[95%CI: -1.5-0.0], p=0.06) but effect size varied according to method used to interpret missingness on the paper bowel diary (sensitivity analysis: -0.9[-1.8-0.0], p=0.04). Secondary outcomes: data suggested successful allocation concealment. Improvements were observed in FI symptoms in the follow-up cohort (at 58 weeks) compared to baseline (approx. 3 fewer FI episodes per week). MEG studies demonstrated bidirectional afferent evoked cortical and efferent induced anal activity that did not vary greatly from control subjects and appeared unchanged by SNM.
Conclusions
The experimental efficacy of SNM remains uncertain. Effects on symptoms observed during double-blinded crossover point to some efficacy over sham, though not large in comparison with placebo responses. The magnitude of effect was highly dependent on interpretation of event recording.