| Objective: |
Primary Clinical Objective
To determine clinical efficacy of sub-sensory sacral neuromodulation (SNM) compared to SHAM
Secondary Clinical Objectives
- To obtain 1 year clinical outcomes of SNM using 2016 optimised therapy (with standardised lead placement)
- To validate new electronic outcome measures and a device to record them
- To improve knowledge of the kinetics of effects of SNM
Mechanistic Objectives
- To identify the biological effect of sub-sensory SNM on underlying anorectal afferent neuronal pathophysiology
- To improve the general understanding of the pathophysiology of faecal incontinence |
| Aim: |
To determine clinical efficacy of sub-sensory chronic low voltage electrical sacral nerve-root stimulation: sacral neuromodulation (SNM) using a commercially-available implantable device, Medtronic Interstim® in adults with faecal incontinence failing conservative treatment. |
| Methods: |
Inclusion Criteria
- Adults aged 18-75
- Meet Rome III and ICI definitions of FI (recurrent involuntary loss of faecal material that is a social or hygienic problem and not a consequence of an acute diarrhoeal illness)
- Failure of non-surgical treatments to the NICE standard
- Minimum severity criteria of 8 FI episodes in a 4 week screening period (this is important to exclude patients who might thence have zero FI episodes during baseline evaluations)
- Ability to understand written and spoken English or relevant language in European centres (due to questionnaire validity)
- Ability and willingness to give informed consent
All patients will have been determined as clinically suitable for SNM based on clinical evaluation and subsequent multidisciplinary team discussion (as mandated by NHS England specialist commissioning guidance).
Exclusion Criteria
A standard list of exclusions (disease variants; surgical fitness, specific contra-indications to implantation) will be used. Note that these are routine clinical exclusions to the use of SNM rather than participation in the research. For completion:
- Known communication between the anal and vaginal tracts
- Prior diagnosis of congenital anorectal malformations
- Previous rectal surgery (rectopexy / resection) performed 12 months ago (24 months for cancer)
- Present evidence of full thickness rectal prolapse
- Prior diagnosis of chronic inflammatory bowel diseases
- Displays symptoms of chronic constipation with over-flow incontinence
- Structural abnormality of the pelvic floor leading to clear evidence of obstructed defaecation based on examination and/or imaging
- Symptoms of significant evacuatory dysfunction based on Obstructive Defecation Syndrome Score ≥8
- Presence of active perianal sepsis (including pilonidal sinus)
- Defunctioning loop or end stoma in situ
- Diagnosed with neurological diseases, such as diabetic neuropathy, multiple sclerosis and Parkinson's disease
- Current or future need for MR imaging based on clinical history
- Complete or partial spinal cord injury
- Bleeding disorders E.g. Haemophiliac, warfarin therapy
- Pregnancy or intention to become pregnant during the study period
- Not fit for preferred method of anaesthesia
- Anatomical limitations that would prevent successful placement of an electrode including congenital abnormalities
- Psychiatric or physical inability to comply with the study protocol (inc. e-diary assessments) at investigator discretion
- Is required to drive for long periods of time for example lorry drivers, taxi drivers and delivery drivers
Study Design
The overall design encompasses a randomised double-blind crossover trial and a follow up cohort study.
Randomised double-blind crossover design:
Ninety eligible participants will be randomly allocated to two study arms after SNM implantation. Both arms have two intervention periods of 16 weeks duration (T0-T16 & T16-T32). Efficacy outcomes are derived from assessments in the final 4 weeks of each crossover period (T12-16 & T28-32) thus allowing for almost 3 months intervention before outcome assessments. A re-programming session will be conducted by the routine clinical care team at 6 weeks in both periods of both arms (T6, T22). Time-points will have an interval tolerance of +/- 1 week for logistical expedience.
Mechanism studies will be performed in a subgroup of consecutively consenting patients equally from both arms (to avoid risk of performance bias) until saturation (n = minimum 20 for both anorectal and anocortical studies) in the final 2 weeks of 4 week assessment periods.
Cohort study: 12 month outcomes
After completing the crossover section of the study patients will continue to be followed up for a further 26 weeks (estimated N=75: allowing for drop outs). During this time they will have ‘open label’ patient decisive stimulation (sub- or supra-sensory) as would be normal for routine clinical practice. Further efficacy outcomes will be recorded at T54-58. While it is accepted that these do not represent true 1-year outcomes (16 weeks has been SHAM treatment during the crossover), these will give an indication of the short-term effectiveness of SNM using the optimised lead placement and within the rigor of a CTU-monitored randomised prospective study. |
| Reason for International Trial: |
The clinical efficacy of SNM has never been rigorously determined in an international trial setting. There is therefore a need for a well-designed study of SNM that seeks to determine definitive proof of clinical effect size and which notably improves on the small number of existing randomised studies and observational data. |