Clinical trial NCT06581341: Enhancing Pelvic Floor Function With Transcranial Magnetic and Tibial Nerve Stimulation for Neurogenic Bladder in MS
Official title: Improvement of Pelvic Floor Function Using Repetitive Transcranial Magnetic Stimulation and Posterior Tibial Nerve Stimulation in Treating Neurogenic Overactive Bladder in Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Neurogenic Overactive Bladder
Multiple Sclerosis
Keywords: Múltiple Sclerosis
Neurogenic Overactive Bladder
Posterior Tibial Nerve Meuromodulation
Repetitive Transcranial Magnetic Stimulation.
Lead sponsor: Sierra Varona SL
Sponsor class: OTHER
Collaborators: name: Universidad Complutense de Madrid
First posted: 2024-09-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: clínical Trials with 3 arms
Primary purpose: TREATMENT

Brief summary: Multiple Sclerosis (MS) is a chronic, autoimmune, inflammatory, and degenerative neurological disorder that affects the central nervous system. Symptoms vary widely depending on the areas impacted and may include fatigue, vision issues, speech difficulties, tremors, limb weakness, loss of sensation, vertigo, coordination problems, and bladder and bowel dysfunction. Among these, lower urinary tract symptoms are particularly common and significantly impact the quality of life for MS patients.

Neurogenic overactive bladder (NOAB) is a prevalent urinary issue in individuals with MS. Treatment options for NOAB include behavioral therapy, β-3 agonists, anticholinergic agents, posterior tibial nerve neuromodulation (PTNM), botulinum toxin injections, sacral root neurostimulation, and surgical interventions.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may improve bladder function by modulating neural activity through an electromagnetic coil placed on the scalp. In contrast, posterior tibial nerve neuromodulation (PTNM) involves electrical stimulation of the spinal cord roots, primarily the S3 segment, to enhance bladder function.

Despite promising evidence, rTMS and PTNM are not yet widely recommended in global guidelines due to the limited number of studies, many of which are case reports. The growing prevalence of overactive bladder underscores the need for effective, non-invasive treatments to improve management and optimize current protocols.

This study aims to evaluate and compare the efficacy of rTMS and tibial nerve stimulation in managing neurogenic overactive bladder in MS patients at Hospital Universitario de la Princesa. The primary objective is to determine whether rTMS is superior, equivalent, or inferior to tibial nerve stimulation in treating NOAB.

The study's hypothesis is that the efficacy of transcranial magnetic stimulation will differ from that of tibial nerve stimulation in managing NOAB in MS patients at Hospital Universitario de la Princesa, with a focus on assessing whether rTMS offers superior, equivalent, or inferior outcomes compared to tibial nerve stimulation. This investigation seeks to provide valuable insights into the effectiveness of these treatment modalities.

Detailed description: Multiple Sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating, and degenerative neurological disease that affects the central nervous system. Symptoms vary widely depending on the areas involved and may include fatigue, blurred vision, speech disturbances, limb weakness, tremors, loss of sensation, vertigo, coordination difficulties, and bladder and bowel dysfunctions. Among these, lower urinary tract symptoms are particularly common and significantly impact the quality of life in MS patients.

Neurogenic overactive bladder (NOAB) is the most prevalent urinary complaint in individuals with MS. Current therapeutic options for NOAB in MS include behavioral therapy, β-3 agonists, anticholinergic agents, posterior tibial nerve neuromodulation (PTNM), botulinum toxin injections, sacral root neurostimulation, and surgical interventions.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may improve bladder function by modulating neural activity through an electromagnetic coil placed on the scalp. Similarly, posterior tibial nerve neuromodulation (PTNM) involves electrical stimulation of the spinal cord roots, mainly the S3 segment, to enhance bladder function.

Although current literature suggests the potential efficacy of both neuromodulation techniques for NOAB, they are not yet widely recommended in global guidelines, largely due to the limited number of studies, many of which are case reports.

The increasing incidence of overactive bladder highlights the urgent need for effective therapeutic interventions. Non-invasive neuromodulation techniques offer promising avenues to enhance treatment outcomes and optimize existing protocols.

This study aims to compare the efficacy of rTMS and tibial nerve stimulation in managing neurogenic overactive bladder in MS patients at Hospital Universitario de la Princesa. The objective is to determine whether rTMS is superior, equivalent, or inferior to tibial nerve stimulation in treating this condition.

The hypothesis posits that the efficacy of transcranial magnetic stimulation will differ from that of tibial nerve stimulation in managing NOAB in MS patients at Hospital Universitario de la Princesa, with the goal of determining whether rTMS is more effective, equally effective, or less effective than tibial nerve stimulation.

Secondary objectives include:

Assessing the efficacy of rTMS in reducing urinary symptoms associated with NOAB in MS patients.

Evaluating the combined effects of transcranial magnetic stimulation and tibial nerve stimulation on urinary symptoms.

Examining the short- and medium-term effects of the treatments on urinary symptoms.

Analyzing the impact of the treatments on the quality of life in MS patients, using the Multiple Sclerosis Quality of Life-54 Questionnaire (MsQoL-54).

Evaluating the applicability of the treatment protocols and analyzing clinical data for future neuromodulation research.

Safety and Adverse Events Monitoring

The study will adhere to current regulatory frameworks governing TMS and PTNS protocols to ensure safety and monitor adverse events. TMS is considered a well-tolerated procedure with minimal adverse effects, even in long-term studies. Commonly observed side effects, which typically resolve within a few days, include headaches, paresthesia, limb pain, restless legs syndrome, increased bladder spasticity, and nonspecific discomfort.

A review of the literature indicates no significant complications associated with percutaneous tibial nerve stimulation (PTNS). However, potential adverse events include skin irritation, increased pain at the stimulation site, rare skin lesions, allergic reactions, and general discomfort.

Any adverse events will be reported to the Ethics Committee and managed according to current safety standards, with monthly documentation. Serious adverse events will be reported immediately.

Safety Protocol

To mitigate potential risks associated with TMS and PTNS, the following safety measures will be implemented:

Proper selection of stimulation intensity and frequency. Precise location of stimulation. Application of aseptic and antiseptic techniques. Monitoring of vital signs (heart rate, blood pressure, oxygen saturation) during and after procedures to detect cardiovascular complications.

Informed consent will be obtained from participants, including comprehensive information about potential risks and the voluntary nature of participation. All personnel involved will be adequately trained in administering the techniques and identifying potential safety issues. All relevant ethical and legal regulations will be observed.

Sample Recruitment

Participants will be recruited through the Rehabilitation Physician, who will inform potential participants about the study during consultations, providing them with a Patient Information Sheet and Informed Consent Form.

Study Design

This study employs a single-blind, randomized clinical trial design. Participants will be randomly assigned to one of three groups:

Group A: rTMS combined with PTNS. Group B: rTMS alone. Group C: PTNS alone. Sealed, opaque, and numbered envelopes will be used to ensure unbiased group assignments. The anticipated start date is one month after receiving Ethics Committee approval.

Transcranial Magnetic Stimulation (TMS) Protocol

The study will use high-frequency TMS at 10 Hz, with a total of 2,000 pulses per session. The treatment duration is 30 minutes, with 12 sessions conducted over 4 weeks (3 sessions per week).

Percutaneous Tibial Nerve Stimulation (PTNS) Protocol

PTNS will involve needle placement 5-6 cm from the medial malleolus, with a pulse duration of 200 µs and a frequency of 20 Hz. Each session will last 30 minutes, with 12 sessions conducted over 4 weeks (3 sessions per week).

Randomization and Blinding

The principal investigator will conduct randomization, while the collaborating investigator will remain unaware of group assignments. The principal investigator will administer the treatments, maintaining single-blind conditions.

Eligibility criteria: Inclusion Criteria:

* Volunteer Adults (Age 18-65)
* Diagnosis of Multiple Sclerosis
* Expanded Disability Status Scale (EDSS) 0-7
* Diagnosis of overactive bladder disfunction secondary to multiple sclerosis

Exclusion Criteria:

* Active urinary tract infection at the time of selection.
* Individuals with a history of urological conditions other than overactive bladder secondary to multiple sclerosis.
* Contraindications for electrical stimulation:
* Presence of metal in the skull
* Intracardiac lines
* History of increased intracranial pressure
* Significant heart disease
* Pacemaker or implantable desfibrillator usage
* Use of implanted medication pumps
* Treatment with tricyclic antidepressants or neuroleptics
* Personal or family history of epilepsy
* Pregnant or breastfeeding women

Primary outcomes:
measure: Reduction in Frequency of Urinary Urgency Episodes
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment..
Secondary outcomes:
measure: Frequency of Urination
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment.t.
measure: Urinary Incontinence
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment.
measure: Expanded Disability Status Scale (EDSS)
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment.
measure: The Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment.
measure: The semi-open question to assess the impact of overactive bladder on daily life.
timeFrame: Participants will complete questionnaires at four time points: 2 weeks before the start of treatment, immediately at the end of treatment, and 4 and 24 weeks post-treatment.
Other outcomes:
Locations:
Study officials:
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Elena Fernández, Physiotherapist
role: PRINCIPAL_INVESTIGATOR
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