Enhancing Pelvic Floor Function With Transcranial Magnetic and Tibial Nerve Stimulation for Neurogenic Bladder in MS

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation
  Repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a non-invasive procedure that uses a magnetic coil placed on the scalp to deliver magnetic pulses to the motor cortex, with the aim of improving bladder function by modulating brain activity associated with bladder control. The MagRex magnetic stimulator with an 8-shaped coil will be used at a frequency of 10 Hz, delivering 2000 pulses per session (6 seconds on, 24 seconds rest protocol) at 90% of the motor threshold. The treatment wil
• Устройство Repetitive Transcranial Magnetic Stimulation
  Repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a non-invasive procedure that uses a magnetic coil placed on the scalp to deliver magnetic pulses to the motor cortex, with the aim of improving bladder function by modulating brain activity associated with bladder control. The MagRex magnetic stimulator with an 8-shaped coil will be used at a frequency of 10 Hz, delivering 2000 pulses per session (6 seconds on, 24 seconds rest protocol) at 90% of the motor threshold. The treatment wil
• Устройство Percutaneous Tibial Nerve Stimulation
  Percutaneous Tibial Nerve Stimulation (PTNM): PTNM involves the use of electrical stimulation applied to the posterior tibial nerve to enhance bladder function by modulating neural pathways. A needle will be placed 5-6 cm proximal to the tibial malleolus, with the following parameters: 200 μs pulse duration, 20 Hz frequency, 30 minutes per session, 3 times per week for 12 weeks. The Neurotrac Pelvitone device will be used.

Первичные конечные точки

• Reduction in Frequency of Urinary Urgency Episodes [Срок оценки: 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..]

Вторичные конечные точки (5)

• Frequency of Urination [Срок оценки: 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.]
• Urinary Incontinence [Срок оценки: 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.]
• Expanded Disability Status Scale (EDSS) [Срок оценки: 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.]
• The Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire [Срок оценки: 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.]
• The semi-open question to assess the impact of overactive bladder on daily life. [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Garcia Lopez FJ, Garcia-Merino A, Alcalde-Cabero E, de Pedro-Cuesta J. Incidence and prevalence of multiple sclerosis in Spain: a systematic review. Neurologia (Engl Ed). 2024 Oct;39(8):639-650. doi: 10.1016/j.nrleng.2022.02.004. Epub 2022 Nov 21. PMID 36410655
• Klineova S, Lublin FD. Clinical Course of Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):a028928. doi: 10.1101/cshperspect.a028928. PMID 29358317
• Pitt D, Lo CH, Gauthier SA, Hickman RA, Longbrake E, Airas LM, Mao-Draayer Y, Riley C, De Jager PL, Wesley S, Boster A, Topalli I, Bagnato F, Mansoor M, Stuve O, Kister I, Pelletier D, Stathopoulos P, Dutta R, Lincoln MR. Toward Precision Phenotyping of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2022 Aug 30;9(6):e200025. doi: 10.1212/NXI.0000000000200025. Print 2022 Nov. PMID 36041861
• Al Dandan HB, Coote S, McClurg D. Prevalence of Lower Urinary Tract Symptoms in People with Multiple Sclerosis: A Systematic Review and Meta-analysis. Int J MS Care. 2020 Mar-Apr;22(2):91-99. doi: 10.7224/1537-2073.2019-030. PMID 32410904
• Erden E, Ersoz M, Tiftik T, Erden E. The neurogenic bladder characteristics and treatment approaches in the patients with multiple sclerosis. Mult Scler Relat Disord. 2022 Feb;58:103439. doi: 10.1016/j.msard.2021.103439. Epub 2021 Dec 3. PMID 34954652
• Hemmett L, Holmes J, Barnes M, Russell N. What drives quality of life in multiple sclerosis? QJM. 2004 Oct;97(10):671-6. doi: 10.1093/qjmed/hch105. PMID 15367738
• Aharony SM, Lam O, Corcos J. Treatment of lower urinary tract symptoms in multiple sclerosis patients: Review of the literature and current guidelines. Can Urol Assoc J. 2017 Mar-Apr;11(3-4):E110-E115. doi: 10.5489/cuaj.4059. Epub 2017 Mar 16. PMID 28360957
• Sousa-Fraguas MC, Lastra-Barreira D, Blanco-Diaz M. Peripheral neuromodulation in women with overactive bladder syndrome: a systematic review. Actas Urol Esp (Engl Ed). 2021 Apr;45(3):177-187. doi: 10.1016/j.acuro.2020.10.003. Epub 2021 Jan 19. English, Spanish. PMID 33353738

Идентификаторы

NCT: NCT06581341 · 0013 · 5465

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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