Title: Tined lead test stimulation to predict long-term benefit from sacral nerve stimulation in patients with chronic constipation (TiLTS-CC).
Funder: Department of Health (England)

Abstract: Background Sacral nerve stimulation (SNS) involves implanting electrodes in the lower spine which are connected to an electrical pulse generator in upper buttock region. SNS is expensive but provides long term relief of symptoms to some patients with medically resistant chronic constipation. Patients are currently selected for SNS through a 2-week evaluation of patient response, using temporary electrodes and an externally attached pulse generator. Using this method, only about 40% of patients receive long term benefit from SNS, threatening the viability of NHS provision. Failure may be due to a short term placebo response or changing electrode position. An enhanced evaluative process using tined lead test stimulation (TiLTS) could improve the proportion of patients benefitting from SNS. Aims The use of a tined (barbed) lead during the evaluative phase allows the same lead to be used for a permanent implant, precluding electrode re-positioning. It also allows a 6-week evaluative phase which can include periods of active and sham stimulation. It is hypothesised that ‘discriminate’ responders (patients responding only to active stimulation) will receive long term benefit from SNS, while patients responding ‘indiscriminately’ (during sham or both periods) will be less likely to benefit. This study will determine whether future use of TiLTS could improve the proportion of patients with refractory idiopathic chronic constipation who receive long-term benefit from SNS. The findings will be used to estimate the cost-effectiveness of TiLTS guided SNS, to inform NHS policy decisions. Plan of Investigation Patients (N=60) with refractory idiopathic chronic constipation will undergo TiLTS for 6 weeks, with 2 weeks of active and sham stimulation separated by a 2 week washout period (no stimulation). The sequence of stimulation (active/sham or sham/active) will be randomly assigned. Stimulation is sub-sensory, and both patients and clinical assessor will remain blind to the stimulation sequence for the duration of the study. Both discriminate and indescriminate responders will be offered permanent SNS; these groups will be compared in terms of treatment benefit at 6 months using a range of patient-centric symptom and quality of life measures. The primary endpoint measure used to assess long-term benefit is a validated disease specific symptom score (PAC-SYM). Potential Impact A small but significant number of patients with chronic constipation become refractory to laxatives, suffering severe symptoms and incurring high personal and NHS costs. Permanent SNS NHS tariffs are £15K-£30K; thus to be financially viable SNS needs to be effectively targeted. Findings from this study have the potential to reduce substantially the rate of ineffective permanent implants. This would reduce the burden of unsuccessful treatment for patients and improve access to those patients most likely to benefit. If successful, TiLTS would be used routinely in patients with refractory chronic constipation in whom other treatment options have failed. Inclusion of an economic model will ensure all stakeholders (patients, clinicians and policy-makers) are addressed.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL