Neurogenic Overactive BladderNCT06581341
Enhancing Pelvic Floor Function With Transcranial Magnetic and Tibial Nerve Stimulation for Neurogenic Bladder in MS
A study testing Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation, Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation in people with Neurogenic Overactive Bladder and Multiple Sclerosis, run by Sierra Varona SL.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Neurogenic Overactive Bladder, Multiple Sclerosis
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation, Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2024to 22 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Neurogenic Overactive Bladder, Multiple Sclerosis
- Being tested
- Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation, Repetitive Transcranial Magnetic Stimulation, Percutaneous Tibial Nerve Stimulation
- Keywords
- Múltiple Sclerosis, Neurogenic Overactive Bladder, Posterior Tibial Nerve Meuromodulation, Repetitive Transcranial Magnetic Stimulation.
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve StimulationDevice
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 will consist of 3 sessions per week over a period of 4 weeks.
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.
Repetitive Transcranial Magnetic StimulationDevice
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 will consist of 3 sessions per week over a period of 4 weeks.
Percutaneous Tibial Nerve StimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Combination of transcranial magnetic stimulation and percutaneous tibial nerve stimulation. Receives: Device: Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation |
| Group 2 | Experimental | Repetitive Transcranial Magnetic Stimulation (rTMS): Receives: Device: Repetitive Transcranial Magnetic Stimulation |
| Group 3 | Experimental | Percutaneous tibial nerve stimulation. Receives: Device: Percutaneous Tibial Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Frequency of Urinary Urgency Episodes
Urgency urinary incontinence is marked by a sudden, intense urge to urinate, often leading to involuntary leakage. This clinical trial focuses on assessing both the presence and severity of urinary urgency in participants.It will be measured using a voiding diary. Participants will receive clear instructions on how to complete the diary, where they will record their daily voiding episodes
Measured: 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 (5)
Frequency of Urination
The term "frequency of urination" is defined as the number of times a person urinates within a specified time period. The frequency of urination exhibited by a participant over the course of a day is a key indicator of overall hydration status.
The measurement of this variable is as follows: A bladder diary will be employed for the purpose of data collection. The participants will be provided with explicit instructions regarding the completion of the diary, which they will utilize to record their daily instances of urination.
Measured: 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
Involuntary micturation of urine, which may manifest as dribbling, minor incontinence episodes, or significant leakage.It will be measured using a validated questionnaire, the Overactive Bladder Symptom Score (OABSS), which assesses the frequency and intensity of urinary urgency, as well as its impact on the participants' quality of life
Measured: 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)
The assessment tool evaluates visual, motor, sensory, sphincteric, and cerebellar functions. The EDSS will be used to measure the effectiveness of a treatment in reducing disease progression and disability across these systems.
Measured: 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
The 54-item questionnaire assesses multiple dimensions of quality of life, including physical function, emotional well-being, mental health, vitality, and social function. The domains deemed pertinent to this study encompass physical function, social function, and emotional well-being.
Measured: 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.
Describe how overactive bladder symptoms affected your daily life and well-being in the past day. Include any specific instances where these symptoms significantly impacted your routine or activities.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start1 Oct 2024 (estimated)
- Primary completion27 Jan 2025 (estimated)
- Study completion22 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Neurogenic Overactive BladderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- clínical Trials with 3 arms
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sierra Varona SL
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad Complutense de Madrid
- Responsible party
- Sponsor
- Investigators
- Elena Fernández, Physiotherapist, Principal investigator, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06581341
- Sponsor's protocol ID
- 0013
- Other IDs
- 5465
- Status last verified
- Aug 2024
- First submitted
- 24 Aug 2024
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36410655Klineova S, Lublin FD. Clinical Course of Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):a028928. doi: 10.1101/cshperspect.a028928.
PubMed 29358317Pitt 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.
PubMed 36041861Al 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.
PubMed 32410904Erden 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.
PubMed 34954652Hemmett 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.
PubMed 15367738Aharony 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.
PubMed 28360957Sousa-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.
PubMed 33353738Canbaz Kabay S, Kabay S, Mestan E, Cetiner M, Ayas S, Sevim M, Ozden H, Karaman HO. Long term sustained therapeutic effects of percutaneous posterior tibial nerve stimulation treatment of neurogenic overactive bladder in multiple sclerosis patients: 12-months results. Neurourol Urodyn. 2017 Jan;36(1):104-110. doi: 10.1002/nau.22868. Epub 2015 Sep 9.
PubMed 26352904Martin-Garcia M, Crampton J. A single-blind, randomized controlled trial to evaluate the effectiveness of transcutaneous tibial nerve stimulation (TTNS) in Overactive Bladder symptoms in women responders to percutaneous tibial nerve stimulation (PTNS). Physiotherapy. 2019 Dec;105(4):469-475. doi: 10.1016/j.physio.2018.12.002. Epub 2018 Dec 18.
PubMed 30862384Ellaway PH, Vasquez N, Craggs M. Induction of central nervous system plasticity by repetitive transcranial magnetic stimulation to promote sensorimotor recovery in incomplete spinal cord injury. Front Integr Neurosci. 2014 May 20;8:42. doi: 10.3389/fnint.2014.00042. eCollection 2014.
PubMed 24904326Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
PubMed 25034472Centonze D, Petta F, Versace V, Rossi S, Torelli F, Prosperetti C, Rossi S, Marfia GA, Bernardi G, Koch G, Miano R, Boffa L, Finazzi-Agro E. Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis. Mult Scler. 2007 Mar;13(2):269-71. doi: 10.1177/1352458506070729. Epub 2007 Jan 29.
PubMed 17439897Pericolini M, Miget G, Hentzen C, Finazzi Agro E, Chesnel C, Lagnau P, Haddad R, Grasland M, Amarenco G. Cortical, Spinal, Sacral, and Peripheral Neuromodulations as Therapeutic Approaches for the Treatment of Lower Urinary Tract Symptoms in Multiple Sclerosis Patients: A Review. Neuromodulation. 2022 Dec;25(8):1065-1075. doi: 10.1111/ner.13525. Epub 2022 Jun 14.
PubMed 34496454Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
PubMed 19833552
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06581341
- Acronym / sponsor ID
- 0013
- Conditions
- Neurogenic Overactive Bladder, Multiple Sclerosis
- Keywords
- Múltiple Sclerosis, Neurogenic Overactive Bladder, Posterior Tibial Nerve Meuromodulation, Repetitive Transcranial Magnetic Stimulation.
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Sierra Varona SLUniversity, hospital or other
- Collaborators
- Universidad Complutense de Madrid
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 27 Jan 2025 (estimated)
- Study completion
- 22 Sep 2025 (estimated)
- First posted
- 3 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
- Model description
- clínical Trials with 3 arms
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Device: Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve StimulationCombination of transcranial magnetic stimulation and percutaneous tibial nerve stimulation. |
| Group 2 | Experimental | Device: Repetitive Transcranial Magnetic StimulationRepetitive Transcranial Magnetic Stimulation (rTMS): |
| Group 3 | Experimental | Device: Percutaneous Tibial Nerve StimulationPercutaneous tibial nerve stimulation. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve StimulationRepetitive 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 will consist of 3 sessions per week over a period of 4 weeks. 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. | Device | Group 1 |
| Repetitive Transcranial Magnetic StimulationRepetitive 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 will consist of 3 sessions per week over a period of 4 weeks. | Device | Group 2 |
| Percutaneous Tibial Nerve StimulationPercutaneous 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. | Device | Group 3 |
Primary outcome
Reduction in Frequency of Urinary Urgency Episodes
Time frame: 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..
Urgency urinary incontinence is marked by a sudden, intense urge to urinate, often leading to involuntary leakage. This clinical trial focuses on assessing both the presence and severity of urinary urgency in participants.It will be measured using a voiding diary. Participants will receive clear instructions on how to complete the diary, where they will record their daily voiding episodes
5 secondary outcomes
Frequency of Urination
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Background: PubMed 36410655Garcia 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.
- Background: PubMed 29358317Klineova S, Lublin FD. Clinical Course of Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):a028928. doi: 10.1101/cshperspect.a028928.
- Background: PubMed 36041861Pitt 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.
- Background: PubMed 32410904Al 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.
- Background: PubMed 34954652Erden 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.
- Background: PubMed 15367738Hemmett 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.
- Background: PubMed 28360957Aharony 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.
- Background: PubMed 33353738Sousa-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.
- Background: PubMed 26352904Canbaz Kabay S, Kabay S, Mestan E, Cetiner M, Ayas S, Sevim M, Ozden H, Karaman HO. Long term sustained therapeutic effects of percutaneous posterior tibial nerve stimulation treatment of neurogenic overactive bladder in multiple sclerosis patients: 12-months results. Neurourol Urodyn. 2017 Jan;36(1):104-110. doi: 10.1002/nau.22868. Epub 2015 Sep 9.
- Background: PubMed 30862384Martin-Garcia M, Crampton J. A single-blind, randomized controlled trial to evaluate the effectiveness of transcutaneous tibial nerve stimulation (TTNS) in Overactive Bladder symptoms in women responders to percutaneous tibial nerve stimulation (PTNS). Physiotherapy. 2019 Dec;105(4):469-475. doi: 10.1016/j.physio.2018.12.002. Epub 2018 Dec 18.
- Background: PubMed 24904326Ellaway PH, Vasquez N, Craggs M. Induction of central nervous system plasticity by repetitive transcranial magnetic stimulation to promote sensorimotor recovery in incomplete spinal cord injury. Front Integr Neurosci. 2014 May 20;8:42. doi: 10.3389/fnint.2014.00042. eCollection 2014.
- Background: PubMed 25034472Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
- Guidelines. Uroweb - European Association of Urology. Retrieved September 5, 2023Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena Fernández, Physiotherapist principal investigator
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation, Repetitive Transcranial Magnetic Stimulation and Percutaneous Tibial Nerve Stimulation in people with Neurogenic Overactive Bladder and Multiple Sclerosis, run by Sierra Varona SL.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact ALBERTO SANCHEZ SIERRA, PhD (+34608801238, alberto.sanchez@uclm.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in Frequency of Urinary Urgency Episodes (time frame: 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..). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06581341, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.