Secondary Bilateral Sacral Nerve Stimulation in Overactive Bladder Patients

Study Overview
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Brief Summary
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Unilateral sacral neuromodulation (SNM) has emerged as a valuable treatment for patient with low urinary tract dysfunction when failure or bad tolerance to anticholinergic treatment for overactive bladder. However, in the medium or long term, some patients failed to benefit from unilateral stimulation (unilateral neuromodulation). A contralateral stimulation could be tested then implanted to restore the efficacy. An other option is to perform a bilateral stimulation of the sacral nerves that could lead to a summation effects better than unilateral stimulation. Therefore, if a unilateral sacral nerve stimulation fails, a contralateral or a bilateral test should be considered.

Detailed Description
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Sacral neuromodulation (SNM) is a treatment in non neurogenic (idiopathic) patients with overactivity of the bladder (OAB) symptoms, refractory to conservative treatment. After selection of patients with positive stimulation test (PNE test), the success rate of stimulation implant is approximatively 70% (40 to 80%). Unilateral versus bilateral initial implantation was retrospectively compared by Pham et al. with respectively 58 and 77% success rate. Wound infection and complication rate were similar. However the limitation of bilateral stimulation is an increased cost for the health care system, augmented duration of the procedure, possible morbidity. Therefore initial implantation in the first step of the treatment is unilateral in current practice. However, after a period of time, a secondary failure may happen, either a complete failure with return to initial symptom or a partial failure with a decrease of the efficacy that may impact on quality of life. However, a non clinical evident effect could have a summation effect if a contralateral stimulator was implanted, and possibly better than contralateral alone. Research have shown in a small study on 15 patients that a selected group of patients appear to benefit from bilateral stimulation test (PNE test) after failure of unilateral S3 stimulation. A successful response was observed in 4/11 (36%) OAB patients. Bilateral stimulation induced a higher clinical response than stimulation of a controlateral lead alone in voiding parameters. In the patients who showed a successful response to PNE test, 3 were implanted bilaterally with more than 50% improvement for 2 of them at one year follow-up, and 41% improvement for the third. No painful stimulation or side effects were reported with chronic bilateral stimulation. In one study, a lead migration was suspected in 3/15 patients and was the cause of failure. Therefore the proposed study will use systematically a tined lead electrode that avoid lead migration. According to these preliminary data, test stimulation with a contralateral lead might be considered in secondary unsuccessful patient and evaluated. Further investigation is necessary to determine in a larger cohort the result of contralateral alone or bilateral stimulator implantation. There is no established guidelines in secondary unsuccessful patients, therefore contralateral stimulation is used in clinical practice according to patient and practitioner opinion. This protocol is presented as a standard clinical practice evaluation.

Official Title
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Secondary Bilateral or Controlateral Sacral Nerve Stimulation in Overactive Bladder Patients With Unilateral Stimulation Failure - Multicenter Study

Conditions
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Bladder Hyperactivity

Intervention / Treatment
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* Device: Device: INTERSTIM II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients implanted with Sacral Neuro Modulation for idiopathic OAB with initial efficacy of at least 3 months following by a failure despite optimization of the stimulation (minimum 3) OAB evaluated by voiding diary: number of frequency ≥ 8/24 h or urgencies ≥ 3 during 3 days, with or without urge incontinence. Age between 18 and 80 years. Exclusion Criteria: Psychiatric or neurologic disabilities on neurologic evaluation. Bladder lithiasis or tumor (cystoscopy or ultrasonography). Treatment by drugs that could interfere with the OAB syndromes. Pelvic floor exercises should have been interrupted 1 month before. No planned surgery on bladder or urinary neurologic tract. Diuresis > 3 liters per 24 hours. Negative test at the end of screening period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alone controlateral stimulation<br>Device: INTERSTIM II Stimulator II activated Stimulator I not activated Measure of efficacy on bladder hyperactivity | Device: Device: INTERSTIM II<br>* A second stimulator is implanted on controlateral site<br>|
| Experimental: 2 sides-stimulation<br>Device: INTERSTIM II Stimulator I and II activated Measure of efficacy on bladder hyperactivity | Device: Device: INTERSTIM II<br>* A second stimulator is implanted on controlateral site<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of Test Period | A successful response is defined as greater than 50% improvement in at least one relevant voiding parameters, with bilateral stimulation versus baseline without stimulation. Relevant voiding diary parameters are: urgency number, frequency, urge incontinence number. These criteria are commonly used in the studies on sacral neuromodulation. | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of alone controlateral stimulation | Effect of alone controlateral stimulation on : urgency, frequency, urge incontinence. | Day 30 and day 60 | 
| Effect of alone controlateral stimulation | Effect of alone controlateral stimulation on : Quality of Life (QoL) scores | Day 30 and day 60 | 
| Effect of alone controlateral stimulation | Effect of alone controlateral stimulation on : VAS pain scale | Day 30 and day 60 | 
| Effect of alone controlateral stimulation | Effect of alone controlateral stimulation on : Adverse events. | Day 30 and day 60 | 
| Effect of alone controlateral stimulation | Prognostic factors of success will be evaluated concerning age, sex, urodynamic parameters, period of time of symptoms before first implant, period of time between first implant and controlateral/bilateral stimulation, complete failure or a partial failure of efficiency of initial stimulator. | Day 30 and day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapse after an initial clinical response