Sacral Neuromodulation for Neurogenic Lower Urinary Tract, Bowel and Sexual Dysfunction

Study Overview
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Brief Summary
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A multi-center double-blinded placebo-controlled randomized clinical trial. The patients will be randomized into two groups. To investigate the efficacy of SNM to improve the key bladder diary variables compared to placebo (i.e. sham) for patients with MS having refractory neurogenic lower urinary tract dysfunction (NLUTD). After first step SNM-procedure and a 3-4 weeks test period patients with more than 50% improvement in the key bladder diary variables will have the IPG implanted. After a month of optimization patients will into two groups: IPG ON or IPG OFF. Period of randomization: four months. Number anticipated to be included: 60 patients

Detailed Description
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Patients with MS often suffer from pelvic-organ dysfunctions, i.e. lower urinary tract (LUT), bowel and sexual dysfunction, aside their cerebral affection. Sacral neuromodulation (SNM) is a reversible minimal invasive procedure affecting the function of the aforementioned pelvic organs. Changes in bladder, bowel and sexual function will be monitored. Primary outcome: Success of SNM for lower urinary tract dysfunction as improvement of at least 50% in the key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to the baseline values. Secondary outcome: To assess the changes in bladder, bowel and sexual function due to SNM by using subjective patient reported outcome measures, quality of life and global assessment score, To assess the changes in urodynamic variables, To assess the safety of SNM for NLUTD and To register the implantation characteristics and the need for reprogramming Data will be collected at Baseline 1: At inclusion Baseline 2: At evaluation after a three weeks test period Baseline 3: At randomization Baseline 4: At the end of study The time frame of the RCT is six months Patients with improvements of bowel symptoms only will be excluded from the trial but followed with the same questionnaires for the same time. The patients will be followed-up every 6 months for a total of 5 years.

Official Title
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Sacral Neuromodulation for Patients With Multiple Sclerosis With Neurogenic Lower Urinary Tract, Bowel and Sexual Dysfunction. A Multicenter Double-blind, Placebo-controlled Randomized Clinical Trial.

Conditions
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Neurogenic Dysfunction of the Urinary Bladder, Multiple Sclerosis, Sacral Neuromodulation, Bowel Dysfunction, Sexual Dysfunction, Quality of Life

Intervention / Treatment
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* Device: Turning ON the neuromodulator
* Device: Turning OFF the neuromodulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory neurogenic lower urinary tract dysfunction (nLUTD) defined by visual analogue scale on treatment satisfaction ranging from 0 to 100 (100 means maximal satisfaction with the current treatment). All patients indicating satisfaction less than 50 are considered non-responders/having refractory overactive bladder (OAB) to current treatment No effect of medical treatment defined by antimuscarinics, beta3-agonist and alpha-blocker. Patients having refractory nLUTD who intend to try SNM for relief of their symptoms Expanded Disability Status Scale (EDSS) < 5 and no progression of neurological disease within 6 months Written informed consent Able to understand the information given about the project Exclusion Criteria: EDSS > 5, neurological disease with severe progression within the last 6 months and/or unable to manage the electronic devices Age < 18 years Any other urological pathology but nLUTD Bladder Pain Syndrome/Interstitial cystitis Any other intestinal or gynecological pathology but neurological conditional symptoms Current pelvic malignancy or clinically significant pelvic mass Previous pelvis radiotherapy Bladder injections with botulinum neurotoxin type A within 6 months before inclusion in trial Unable to manage the electronic devices Inability to give an informed consent

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: Parallel Assignment
Interventional Model Description: After the implantation of the IPG the patients will be grouped into three strata: Patients with urgency frequency syndrome and/or urgency incontinence: at least 50% decrease in number of voids and/or number of leakages and/or increased voided volume and/or more than 50% reduction in pad weight Patients with chronic urinary retention: at least 50% decrease in post void residual and/or reduction in number of CISC Patients with a combination of urgency frequency syndrome and/or urgency incontinence and chronic urinary retention: at least 50% decrease in number of voids and/or number of leakages and/or more than 50% reduction in pad weight, and/or at least 50% decrease in post void residual and/or a reduction in number of CISC After four months all IPG´s are turned on.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IPG turned ON<br>Continous neuromodulation | Device: Turning ON the neuromodulator<br>* IPG on<br>* Other names: INTERSTIM X SYSTEM;|
| Placebo Comparator: IPG turned OFF<br>No neuromodulation | Device: Turning OFF the neuromodulator<br>* IPG OFF<br>* Other names: INTERSTIM X SYSTEM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of SNM for neurogenic lower urinary tract dysfunction | Success is defined as improvement of at least 50% in the key bladder diary variables, i.e. number of voids and/or number of leakages, post void residual volumen, compared to the baseline values using BLADDER DIARY for three days before inclusion and at evaluation. | Six months | 
| Male bladder function | Male lower urinary tract symptoms (MLUTS) by standard International Consultation on Incontinence Questionnaire (ICIQ)-MLUTS 10/06. Scale ranges from 0 to 44 points. Higher score indicate greater impact of individual symptoms for the patient. Changes will be compared to basal data. | Six months | 
| Female bladder function | Female lower urinary tract symptoms (FLUTS) by standard questionnaire ICIQ-FLUTS 12/07. Scale ranges from 0 to 48 points. Higher score indicate greater impact of individual symptoms for the patient. Changes will be compared to basal data. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bladder volume | Change in bladder volume measured in ml before and after implantation of implantable pulse generator for sacral neuromodulation | Six months | 
| Changes in bladder sensation Mangler | Changes in bladder sensation measured in ml before and after implantation of implantable pulse generator for sacral neuromodulation | Six months | 
| Bowel function | Bowel function by standard questionnaire ICIQ-B (04/08). Scale ranges from 0 to 75 points. Higher score indicate greater impact of individual symptoms for the patient. Changes will be compared to basal data. | Eight months | 
| Male sexual function | Male sexual function by standard questionnaire (07/05). Scale ranges from 0 to 12 points. Higher score indicate greater impact of individual symptoms for the patient. Changes will be compared to basal data. | Six months | 
| Female sexual function | Female sexual function by standard questionnaire (09/05). Scale ranges from 0 to 14 points. Higher score indicate greater impact of individual symptoms for the patient. Changes will be compared to basal data. | Six months | 
| Quality of life by standard questionnaire EQ-5D-5L | The EQ-5D-5L is a standard measure of health-related quality of life. EQ-5D-5L consists of two components: a health state profile and a visual analog scale (VAS). EQ-5D health state profile comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where a higher score indicates a better health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating the worst health you can imagine and 100 indicating the best health you can imagine. Higher scores of EQ VAS indicate better health | Six months |