Repetitive Transcranial Magnetic Stimulation in Women With Overactive Bladder With Urgency Incontinence

NCT05099419 | Unknown Early Phase 1 FDA Device

• 1 other identifier: HS-21-00578
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Overactive bladder (OAB) affects an estimated 16-30% of women in the US and urgency urinary incontinence (UUI) affects 7-11% of women with OAB. It is known that repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) can modulate the pelvic floor muscle activity with potential benefits for various urologic conditions. The goal of this study is to assess feasibility of rTMS as a treatment option for OAB with UUI by determining which rTMS frequency is most effective in targeting sensory components of OAB, namely urinary urgency, and also in targeting the brain network known to be involved in OAB.

Conditions

Overactive Bladder; Urge Incontinence

Keywords

Repetitive Transcranial Magnetic Stimulation; Overactive Bladder; Urge Incontinence

Outcome Measures

Primary Outcomes (6)

• Effects of repetitive transcranial magnetic stimulation (rTMS) on pelvic-supplementary motor area (SMA) activity after low-frequency rTMS

  The effects of low-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes.

  Functional MRI lasting 30 minutes will be obtained immediately before low-frequency rTMS during weeks 2 and 3.

• Effects of repetitive transcranial magnetic stimulation (rTMS) on pelvic-supplementary motor area (SMA) activity after low-frequency rTMS

  The effects of low-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes.

  Functional MRI lasting 30 minutes will be obtained within 30 minutes of finishing low-frequency rTMS during weeks 2 and 3.

• Effects of rTMS on pelvic-SMA activity after high-frequency rTMS

  The effects of high-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes.

  Functional MRI lasting 30 minutes will be obtained immediately before high-frequency rTMS during weeks 2 and 3.

• Effects of rTMS on pelvic-SMA activity after high-frequency rTMS

  The effects of high-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes.

  Functional MRI lasting 30 minutes will be obtained within 30 minutes of finishing high-frequency rTMS during weeks 2 and 3.

• Effects of rTMS on pelvic floor muscle activity after low-frequency rTMS

  The effects of low-frequency rTMS on pelvic floor muscle activity will be evaluated with pelvic floor electromyography (EMG) obtained with a rectal sensor during the low-frequency rTMS session.

  Pelvic floor EMG will be obtained during low-frequency rTMS session, lasting 33 minutes, during weeks 2 and 3.

• Effects of rTMS on pelvic floor muscle activity after high-frequency rTMS

  The effects of high-frequency rTMS on pelvic floor muscle activity will be evaluated with pelvic floor electromyography (EMG) obtained with a rectal sensor during the high-frequency rTMS session.

  Pelvic floor EMG will be obtained during high-frequency rTMS session, lasting 20 minutes, during weeks 2 and 3.

Secondary Outcomes (4)

• Assess subjective OAB and UUI symptom changes following rTMS

  Subjective OAB and UUI symptoms will be assessed with the OAB-q at baseline during week 1.

• Assess subjective OAB and UUI symptom changes following rTMS

  Subjective OAB and UUI symptoms will be assessed with the OAB-q after rTMS treatments during weeks 2 and 3.

• Assess objective OAB and UUI symptom changes following rTMS

  Objective OAB and UUI symptoms will be assessed with a bladder diary at baseline during week 1.

• Assess objective OAB and UUI symptom changes following rTMS

  Objective OAB and UUI symptoms will be assessed with a bladder diary after rTMS treatments during weeks 2 and 3.

Other Outcomes (1)

• Feasibility of repetitive transcranial magnetic stimulation (rTMS) use in women with overactive bladder (OAB) and urgency urinary incontinence (UUI)

  Feasibility will be assessed after completion of the study, up to 6 months.

Study Arms (2)

High Frequency rTMS Protocol

EXPERIMENTAL

High frequency with 10 Hz at 80% motor threshold intensity with figure-of-eight coil for a total of 2,000 pulses. Pulses will be delivered in 10-second trains with a 50-second pause between the trains.

Device: Repetitive Transcranial Magnetic Stimulation

Low Frequency rTMS Protocol

EXPERIMENTAL

Low frequency 1 Hz at 80% motor threshold intensity with figure-of-eight coil for a total of 2,000 pulses. Pulses will be delivered continuously.

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

rTMS uses pulses of magnetic energy to non-invasively stimulate the brain. The rTMS device to be used in this study is the Magstim Rapid2 Plus1. The rTMS device is connected to an active figure-of-eight coil which rests against the scalp and delivers the magnetic energy to the brain. The rTMS protocol is specified by the parameters of pulse frequency, duration of continuous pulse delivery, intensity, and stimulation location. Each participant will receive two different standard rTMS protocols that have been used in past research studies for modulation of pelvic floor tone delivered over the motor cortex in an area that is known to control pelvic floor muscles.

High Frequency rTMS Protocol; Low Frequency rTMS Protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• female
• diagnosis of overactive bladder with symptoms of urgency urinary incontinence majority of the time during the last 3 months

You may not qualify if:

• current use of sacral neuromodulation
• new initiation of overactive bladder treatment within the last 6 weeks
• has had intradetrusor onabotulinumtoxinA injections in the last 3 months
• neurological disease affecting the bladder or bowel
• incomplete bladder emptying
• history of urologic cancer
• active infection
• history of cystitis caused by tuberculosis, radiation, or chemotherapies
• severe pelvic pain
• pregnancy
• post-partum 6 weeks
• post-surgical 6 weeks
• cannot undergo MRI
• history of epilepsy or seizures

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Related Publications (14)

• Reynolds WS, Fowke J, Dmochowski R. The Burden of Overactive Bladder on US Public Health. Curr Bladder Dysfunct Rep. 2016 Mar;11(1):8-13. doi: 10.1007/s11884-016-0344-9. Epub 2016 Jan 23.

  PMID: 27057265 BACKGROUND

• Burgio KL, Locher JL, Goode PS, Hardin JM, McDowell BJ, Dombrowski M, Candib D. Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAMA. 1998 Dec 16;280(23):1995-2000. doi: 10.1001/jama.280.23.1995.

  PMID: 9863850 BACKGROUND

• Lightner DJ, Gomelsky A, Souter L, Vasavada SP. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019 Sep;202(3):558-563. doi: 10.1097/JU.0000000000000309. Epub 2019 Aug 8.

  PMID: 31039103 BACKGROUND

• Yani MS, Fenske SJ, Rodriguez LV, Kutch JJ. Motor cortical neuromodulation of pelvic floor muscle tone: Potential implications for the treatment of urologic conditions. Neurourol Urodyn. 2019 Aug;38(6):1517-1523. doi: 10.1002/nau.24014. Epub 2019 May 1.

  PMID: 31044482 BACKGROUND

• Griffiths D. Imaging bladder sensations. Neurourol Urodyn. 2007 Oct;26(6 Suppl):899-903. doi: 10.1002/nau.20488.

  PMID: 17654564 BACKGROUND

• Blok BF, Willemsen AT, Holstege G. A PET study on brain control of micturition in humans. Brain. 1997 Jan;120 ( Pt 1):111-21. doi: 10.1093/brain/120.1.111.

  PMID: 9055802 BACKGROUND

• Griffiths D, Tadic SD, Schaefer W, Resnick NM. Cerebral control of the bladder in normal and urge-incontinent women. Neuroimage. 2007 Aug 1;37(1):1-7. doi: 10.1016/j.neuroimage.2007.04.061. Epub 2007 May 18.

  PMID: 17574871 BACKGROUND

• Griffiths D, Clarkson B, Tadic SD, Resnick NM. Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training. J Urol. 2015 Sep;194(3):708-15. doi: 10.1016/j.juro.2015.03.102. Epub 2015 Mar 28.

  PMID: 25828973 BACKGROUND

• Tadic SD, Griffiths D, Schaefer W, Murrin A, Clarkson B, Resnick NM. Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn. 2012 Jun;31(5):652-8. doi: 10.1002/nau.21240. Epub 2012 Mar 30.

  PMID: 22473921 BACKGROUND

• Brusa L, Finazzi Agro E, Petta F, Sciobica F, Torriero S, Lo Gerfo E, Iani C, Stanzione P, Koch G. Effects of inhibitory rTMS on bladder function in Parkinson's disease patients. Mov Disord. 2009 Feb 15;24(3):445-8. doi: 10.1002/mds.22434.

  PMID: 19133657 BACKGROUND

• Nizard J, Esnault J, Bouche B, Suarez Moreno A, Lefaucheur JP, Nguyen JP. Long-Term Relief of Painful Bladder Syndrome by High-Intensity, Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right and Left Dorsolateral Prefrontal Cortices. Front Neurosci. 2018 Dec 11;12:925. doi: 10.3389/fnins.2018.00925. eCollection 2018.

  PMID: 30618554 BACKGROUND

• Lefaucheur 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.

  PMID: 25034472 BACKGROUND

• Stultz DJ, Osburn S, Burns T, Pawlowska-Wajswol S, Walton R. Transcranial Magnetic Stimulation (TMS) Safety with Respect to Seizures: A Literature Review. Neuropsychiatr Dis Treat. 2020 Dec 7;16:2989-3000. doi: 10.2147/NDT.S276635. eCollection 2020.

  PMID: 33324060 BACKGROUND

• Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019 Aug;130(8):1409-1416. doi: 10.1016/j.clinph.2019.03.016. Epub 2019 Apr 6.

  PMID: 31104898 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Incontinence, Urge

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urinary Incontinence; Urination Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Larissa Rodriguez, MD

  University of Southern California

  STUDY DIRECTOR

Central Study Contacts

Rita Jen, MD

CONTACT

626-720-4051; ritajen@usc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Urology

Model Details: Two different intervention protocols will be administered in a crossover design.

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 29, 2021
• Study Start: October 28, 2021
• Primary Completion: April 30, 2022
• Study Completion: June 30, 2022
• Last Updated: November 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)