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

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.

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

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Multiple Sclerosis; Sexual Dysfunction; Bowel Dysfunction; Neurogenic Dysfunction of the Urinary Bladder; Sacral Neuromodulation
• Intervention / Treatment: Device: Turning ON the neuromodulator; Device: Turning OFF the neuromodulator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hanne Kobberø; Phone Number: 004565414400; Email: hanne.kobberoe2@rsyd.dk
• Study Contact Backup: Name: Mads H Poulsen; Phone Number: 004565414400; Email: mads.poulsen@rsyd.dk

Study Locations

• Denmark
  • Fyn
    • Odense, Fyn, Denmark, 5000
      • Recruiting
      • Odense University Hospital
      • Contact: Hanne Kobberø; Phone Number: +4565414400; Email: hanne.kobberoe2@rsyd.dk
      • Contact: Mads H Poulsen; Phone Number: +4565414400; Email: mads.poulsen@rsyd.dk
      • Principal Investigator: Hanne Kobberø

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IPG turned ON; Continous neuromodulation	Device: Turning ON the neuromodulator; IPG on; Other Names: INTERSTIM X SYSTEM
Placebo Comparator: IPG turned OFF; No neuromodulation	Device: Turning OFF the neuromodulator; IPG OFF; Other Names: INTERSTIM X SYSTEM

What is the study measuring?

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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Rate of adverse events evaluated by the Medical Device Coordination Group, (MDCG)-202010/1, safety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745	Six months
Global assessment scale	5 point Likert scale evaluated by: Very satisfied - satisfied - neutral - unsatisfied - very unsatisfied	Six months
Implantation Characteristics	The lowest stimulation value in mA will be monitored and number of the re-programming	Six months

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Copenhagen; University of Ostrava; Université de Nantes
• Investigators: Principal Investigator: Hanne Kobberø, Odense University Hospital; Study Director: Mads H Poulsen, Odense University Hospital; Study Chair: Morten Blaabjerg, Odense University Hospital; Study Chair: Helle H Nielsen, Odense University Hospital; Study Chair: Mikkel Fode, Herlev/Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: May 15, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Urinary Bladder Diseases; Multiple Sclerosis; Sclerosis; Intestinal Diseases; Urinary Bladder, Neurogenic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents
• Other Study ID Numbers: OdenseOUH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study plan will be uploaded online at the Data Management Plan (DMP) Online of the University of Southern Denmark. See website below.
• IPD Sharing Time Frame: From 2027 and for ten years
• IPD Sharing Access Criteria: Log in to DMP is required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes