A randomized double-blinded sham-controlled cross-over trial of tined-lead sacral nerve stimulation testing for chronic constipation

Abstract

ObjectivesSacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering chronic constipation. Patients are currently selected for SNS using a 2week peripheral nerve evaluation (PNE) comprising stimulation via temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. MethodsA randomised double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients demonstrating a reduction ≥ 0.5 in constipation symptom score (PAC-SYM) at 6 months. ResultsA total of 45 patients were randomised, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, 7 (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were non-responders. Six patients were withdrawn during the test phase due to infection or non-compliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60% vs 57%, p=0.76). The study was terminated prematurely due to a persistent infection rate of 10 (22%) during ePNE of which 9 (20%) were severe. ConclusionsePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6 week PNE poses a high risk of infection.

Mechanisms, Evaluation, and Management of Chronic Constipation

“…158 Contrary to findings from uncontrolled studies, 159 findings from more rigorous studies [160][161][162] and from a double-blind study of 45 patients with constipation are less encouraging. 163 Sacral nerve stimulation is therefore not recommended for treating refractory constipation. Poor-quality studies found that rectal suspension procedures, a form of rectopexy, might improve symptoms and also be accompanied by healing of prolapse-associated solitary rectal ulcer syndrome in patients with refractory constipation and rectal intussusception.…”

Effects of temporary sacral nerve stimulation on gastrointestinal motility and function in patients with chronic refractory slow-transit constipation

“…The long-term outcome of these patients is now available, showing that two of them (both young females, candidates for total colectomy) are still using the SNS with moderate benefits. However, a placebo effect and the willingness to believe in an advanced therapy like SNS could explain these findings [33,34]. The effects of depressive disorders demonstrated by the MMPI questionnaire in the response rate to SNS has also been considered recently, and it has been shown that a minority of constipated patients with normal MMPI could potentially benefit from permanent SNS [32].…”

Bioelectronic medicine for the autonomic nervous system: clinical applications and perspectives

“…SNM was shown to be a beneficial and cost-effective intervention in different subtypes of patients suffering from faecal incontinence refractory to standard treatments in both short- [79,80,86,89,90] and long-term [108,139,140] studies, receiving regulatory approval in most major health systems [95,141]. On the other hand, after being shown to be effective in the treatment of idiopathic slow-and normaltransit constipation resistant to conservative treatment in preliminary studies [75,142], SNM showed no superiority to sham stimulation in controlled trials [97][98][99].…”

“…To date, a positive PNE test remains the sole predictor for the long-term efficacy of SNM [90,131,147]. However, for some diseases, such as chronic constipation, a positive PNE seems not to be a good predictor of success [97][98][99][100], as in other conditions, where still the nonresponder rates after the implantation of a chronic neuromodulator can be as high as 40% [106,133,147]. One reason for this could be the standard unipolar wire electrode itself, which is significantly thinner than the standard permanent quadripolar electrode, leading to a greater risk of electrode dislocation.…”