Noninvasive Spinal Cord Stimulation for Neurogenic and Idiopathic Overactive Bladder

Evaluation of Noninvasive Spinal Cord Stimulation for Neurogenic and Idiopathic Overactive Bladder

Overactive bladder (OAB) affects 12-30% of the world's population. The accompanying urinary urgency, urinary frequency and incontinence can impair the ability to work, interact in social activities and can result in poor social functioning. Multiple treatment modalities are available for overactive bladder. However, each therapy has drawbacks that limit its application in certain patient populations. For example, oral medications have significant side effects and suffer from poor adherence. Botulinum toxin injection into the bladder wall is invasive, requires re-treatment on a regular basis and carries a risk of urinary retention. Current neuromodulatory techniques are invasive and require highly-specialized care. Therefore, a need exists for a non-invasive, well-tolerated and easily administered therapy for OAB. Transcutaneous spinal cord stimulation (TSCS) has been developed and tested in able bodied individuals to initiate locomotor function as well as in the SCI population for lower extremity and upper extremity function. More recently, we have tested this SCI patients to enable lower urinary tract function and decrease detrusor overactivity, resulting in improved continence.

Study Overview

• Status: Withdrawn
• Conditions: Overactive Bladder; Neurogenic Bladder; Incontinence, Urge
• Intervention / Treatment: Device: Noninvasive spinal cord stimulation

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 18 and 80 years

2. Known diagnosis of overactive bladder, confirmed by:

   • presence of urinary frequency, urgency
   • frequent small-volume voids on frequency-volume chart
   • high score on ICIQ-OAB, ICIQ-OABQOL, and OAB-q questionnaires

Exclusion Criteria:

1. Younger than 18 years of age
2. Older than 80 years of age
3. Presence of lower urinary tract symptoms suggestive of urinary retention or obstruction
4. Finding of an elevated post-void residual (>100 ml) on an ultrasonographic bladder scan
5. History of spinal cord injury, spina bifida or other neurological disease affecting the spinal cord
6. Acute or current urinary tract infection
7. History of neuromodulation for overactive bladder (sacral nerve stimulation or peripheral tibial nerve stimulation)
8. Current or planned pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham stimulation	Device: Noninvasive spinal cord stimulation; Noninvasive spinal cord stimulation is a transcutaneous technique used to modulate the activity of the spinal cord. Subjects will undergo sham or actual stimulation 3-4 times a week for one hour at a time.
Experimental: Actual stimulation; Subjects enrolled in the	Device: Noninvasive spinal cord stimulation; Noninvasive spinal cord stimulation is a transcutaneous technique used to modulate the activity of the spinal cord. Subjects will undergo sham or actual stimulation 3-4 times a week for one hour at a time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of urination and incontinence episodes over 72 hours	A voiding diary records the amount of fluid intake, the number of urinations and the number of incontinence episodes over 72 hours. The number of daily urinations and incontinence episodes will be compared at the beginning and the conclusion of the study. Changes in the number of daily urinations and incontinence episodes will be compared between participants in the stimulation and sham arms of the study.	4-12 weeks
Score on overactive bladder questionnaires	Each participant will complete two validated questionnaires pertaining to overactive bladder: OAB-q and ICIQ-OAB. The OAB-q generates a total score ranging between 33 points (best) to 198 points (worst). The ICIQ-OAB generates a total score ranging between 0 points (best) to 58 points (worst). The questionnaires will be completed at the initiation and completion of the study. Change in questionnaire scores between initiation and completion of the study will be assessed. Changes in questionnaire scores will be compared between participants in the stimulation and sham arms of the study.	4-12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cystometric bladder capacity, number of detrusor overactivity episodes during urodynamic studies.	Urodynamic studies will be performed at the initiation and completion of the study. Urodynamic studies will be performed according to ICS (International Continence Society) criteria. Changes in cystometric capacity and number of detrusor overactivity episodes between initiation and completion of the study will be assessed. Changes in these parameters will be compared between participants in the stimulation and sham arms of the study.	4-12 weeks

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: University of California, Los Angeles
• Investigators: Principal Investigator: Evgeniy I Kreydin, University of Southern California

Publications and helpful links

General Publications

• Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006 Dec;50(6):1306-14; discussion 1314-5. doi: 10.1016/j.eururo.2006.09.019. Epub 2006 Oct 2.
• Gerasimenko Y, Gorodnichev R, Moshonkina T, Sayenko D, Gad P, Reggie Edgerton V. Transcutaneous electrical spinal-cord stimulation in humans. Ann Phys Rehabil Med. 2015 Sep;58(4):225-231. doi: 10.1016/j.rehab.2015.05.003. Epub 2015 Jul 20.
• Gad PN, Kreydin E, Zhong H, Latack K, Edgerton VR. Non-invasive Neuromodulation of Spinal Cord Restores Lower Urinary Tract Function After Paralysis. Front Neurosci. 2018 Jun 29;12:432. doi: 10.3389/fnins.2018.00432. eCollection 2018.
• Yoshimura N, Miyazato M, Kitta T, Yoshikawa S. Central nervous targets for the treatment of bladder dysfunction. Neurourol Urodyn. 2014 Jan;33(1):59-66. doi: 10.1002/nau.22455. Epub 2013 Jul 5.
• Zhong H, Liu E, Kohli P, Perez L, Edgerton VR, Ginsberg D, Gad P, Kreydin E. Noninvasive spinal neuromodulation mitigates symptoms of idiopathic overactive bladder. Bioelectron Med. 2022 Mar 23;8(1):5. doi: 10.1186/s42234-022-00087-x.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 24, 2020
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 22, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Neurologic Manifestations; Urination Disorders; Urinary Incontinence; Urinary Bladder, Overactive; Urinary Bladder, Neurogenic; Urinary Incontinence, Urge
• Other Study ID Numbers: HS-18-00382

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No