Amplifying Sensation in Underactive Bladder

Not Applicable

Completed

• Conditions: Urinary Bladder, Underactive
• Interventions: Device: Neurometer Neurotron CPT; Procedure: Cystometry; Procedure: Pressure-flow study

• Registration Number: NCT04516434
• Lead Sponsor: Duke University

Brief Summary

The purpose of this study is to determine the influence of intravesical (bladder) electrical stimulation and intraurethral electrical stimulation on bothersome symptoms and bladder function in neurologically-intact adult women with underactive bladder. The investigators hypothesize that electrical stimulation will decrease bothersome urinary symptoms relative to baseline and increase voided percentage during pressure-flow studies compared to their routine clinical exam.

Detailed Description

1. Objective: The overall objective of this study is to improve lower urinary tract symptoms (LUTS) in adult neurologically-intact women with underactive bladder through electrical stimulation of bladder sensory nerves or urethral sensory nerves.

2. Background and Significance: The storage and elimination of urine is regulated by neural circuits in the brain and spinal cord to coordinate function between the urinary bladder and the urethra. During micturition (bladder emptying), the elimination of urine is facilitated by bladder muscle (detrusor) contraction and urethral and pelvic floor muscle relaxation. Urine flow through the urethra also activates sensory nerves to amplify bladder contractions and maintain efficient bladder emptying. Incomplete emptying and urinary retention occur when these mechanisms are disrupted or poorly coordinated.

Incomplete emptying due to underactive bladder is a poorly understood health concern that symptomatically affects up to 40% of the population, with the highest prevalence of symptoms in older men and women. Despite the high prevalence of symptoms, the diagnosis of an underactive bladder remains low due to the lack of consistent terminology and standardized diagnostic criteria. This results in defining underactive bladder by a symptom complex that may involve reduced motor drive (detrusor underactivity) during bladder emptying and/or reduced sensory drive during filling and emptying. Symptoms experienced by persons with underactive bladder include nocturia, urinary frequency, urgency, incontinence, slow stream, hesitancy, straining, and sensation of incomplete emptying. The most common symptoms are nocturia, slow stream, frequency, hesitancy, and the impact of these symptoms on quality of life is substantial for many patients.

The management options for persons with underactive bladder include double-void, intermittent self-catheterization, or pharmacotherapy. However, these treatments are associated with poor quality of life and patients often fail to completely resolve the lower urinary tract symptoms (LUTS). There is a need to clarify the pathological mechanisms underlying underactive bladder to improve therapeutic outcomes. One approach to clarify reduced sensory drive is to evaluate the functional integrity of sensory nerves with quantitative sensory testing. Current perception threshold (CPT) testing delivers electrical stimulation to activate nerve fibers that evoke sensory perception, and changes in bladder sensory pathways were demonstrated in persons with diabetic detrusor underactivity. These diagnostic tests, however, have not been applied to neurologically intact adult women with underactive bladder and may provide insight into pathological sensory dysfunction.

The proposed research will quantify sensory nerve sensitivity in the bladder and urethra in adult women with underactive bladder. The investigators will then amplify sensory nerve activity via continuous electrical stimulation to improve LUTS associated with underactive bladder. Achieving the proposed objectives will establish a prognostic marker for rationally guided electrical stimulation in women with underactive bladder. Understanding how these mechanisms contribute to impaired emptying in underactive bladder will enable the development of novel therapeutics to enhance quality of life.

3. Subject Recruitment: Established patients with underactive bladder will be identified by MaestroCare chart review. New patients with underactive bladder will be identified by Duke urogynecologists who see patients at one of two urogynecologic offices (Navaho Clinic in Raleigh or Patterson Place in Durham).

4. Design and Procedures: The investigators will perform a parallel interventional study with two non-randomized study arms (bladder stimulation and urethral stimulation). Potential participants will be screened remotely by email via RedCap by completing a questionnaire to determine bothersome symptoms and perceptions of bladder function. Potential participants that meet eligibility criteria will be scheduled for an in person study procedure visit, where informed consent will be signed. Participants will then undergo current perception threshold (CPT) testing, where electrical stimulation will be delivered via a catheter to the urethra (intraurethral) and bladder (intravesical) to evoke sensation. The CPT results will inform whether the participant receives an investigational session of intravesical (bladder) electrical stimulation or intraurethral electrical stimulation. Following electrical stimulation, the participant will undergo urodynamic studies (cystometrogram, pressure-flow study) to assess bladder function after the investigational stimulation procedures. The participant will also be asked to complete remotely by email a post-study symptom RedCap questionnaire 7 days after study completion.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-08-13
• Study First Submitted QC: 2020-08-15
• Study First Posted: 2020-08-18
• Study Start: 2021-09-01
• Primary Completion: 2024-09-04
• Study Completion: 2024-09-27
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

• Females ages 18 and older

• Able to provide informed consent and agree to the study risks

• Willing to withdraw from medications affecting urination for the 48 hours prior to the procedure (e.g., alpha-adrenergic antagonists, cholinergic agonists, cholinesterase inhibitors)

• Has the below response to 2 of the 3 questions:

  1. Questions regarding self-reported poor sensation during bladder filling or emptying (one or more of the below)

     • In the past 7 days, where did the participant feel sensations when needing to urinate? Answer: "No" response for Bladder Area
     • In the past 7 days, how often did the participant have no sensation of urine flow while urinating? Answer: "Most of the time" or "Every time" response
     • In the past 7 days, how often did the participant feel that the bladder was not completely empty after urination? Answer: "Most of the time" or "Every time" response

  2. Questions regarding self-reported bothersome urinary symptoms (one or more of the below)

     • In the past 7 days, how satisfied was the participant with bladder function? Answer: "Not at all satisfied" or "Somewhat satisfied" response
     • In the past 7 days, how bothered was the participant by urinary symptoms? Answer: "Very bothered" or "Extremely bothered" response

  3. Standard uroflowmetry with a voiding efficiency (voided volume / voided volume + residual volume) of < 80%, voided volume + residual volume must be >150ml for measurement

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Exclusion Criteria

• Preexisting neurological impairment (e.g., spinal cord injury, multiple sclerosis, Guillain-Barre, cauda equina syndrome, cerebrovascular accident, Parkinson's disease, traumatic brain injury)
• Functional obstruction demonstrated by either elevated pelvic floor activity on EMG during standard pressure flow study or high tone pelvic floor on clinical exam)
• Pelvic organ prolapse beyond introitus
• Active urinary tract infection (candidate would be deferred until treated)
• Positive pregnancy test
• Less than 6 weeks postpartum
• Unevaluated hematuria
• Urethral stricture/stenosis
• Surgical obstruction i.e., urinary retention due to obstructive sling or other anti incontinence procedure
• Surgical procedures to increase bladder capacity (e.g., augmentation cystoplasty)
• Active sacral neuromodulation or ongoing posterior tibial nerve stimulation sessions
• Botulinum toxin injection in the past six months
• History of genitourinary or gastrointestinal cancer

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intraurethral Electrical Stimulation	Pressure-flow study	This procedure is specific to the urethral stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the urethra and positioned with the electrode contact 10-14 mm from the bladder neck to stimulate the proximal urethra. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be 2-20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to the proximal urethra at "strong desire to void" during cystometry. The participant will then be given permission to void at "maximum cystometric capacity" with continuous intraurethral stimulation.
Intravesical Electrical Stimulation	Pressure-flow study	This procedure is specific to the bladder stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the bladder through the urethra and the electrode contacts will be positioned to be floating within the bladder. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be set at 20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to bladder sensory nerves for up to 60 minutes prior to the start of urodynamic studies.
Intraurethral Electrical Stimulation	Neurometer Neurotron CPT	This procedure is specific to the urethral stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the urethra and positioned with the electrode contact 10-14 mm from the bladder neck to stimulate the proximal urethra. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be 2-20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to the proximal urethra at "strong desire to void" during cystometry. The participant will then be given permission to void at "maximum cystometric capacity" with continuous intraurethral stimulation.
Intravesical Electrical Stimulation	Cystometry	This procedure is specific to the bladder stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the bladder through the urethra and the electrode contacts will be positioned to be floating within the bladder. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be set at 20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to bladder sensory nerves for up to 60 minutes prior to the start of urodynamic studies.
Intraurethral Electrical Stimulation	Cystometry	This procedure is specific to the urethral stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the urethra and positioned with the electrode contact 10-14 mm from the bladder neck to stimulate the proximal urethra. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be 2-20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to the proximal urethra at "strong desire to void" during cystometry. The participant will then be given permission to void at "maximum cystometric capacity" with continuous intraurethral stimulation.
Intravesical Electrical Stimulation	Neurometer Neurotron CPT	This procedure is specific to the bladder stimulation arm. A sterile stimulation catheter (custom, 7-French) will be placed in the bladder through the urethra and the electrode contacts will be positioned to be floating within the bladder. A single return electrode will also be placed on the abdominal skin above the pubic bone. Stimuli will be delivered as 0.2 ms charge-balanced biphasic rectangular current pulses. Stimulation frequency will be set at 20 Hz and amplitude will be adjusted individually to 80% of the maximum tolerable intensity. Electrical stimulation will be applied to bladder sensory nerves for up to 60 minutes prior to the start of urodynamic studies.

Primary Outcome Measures

Name	Time	Method
Voided Percentage	pressure-flow study, up to 30 minutes	Use of intraurethral electrical stimulation or intravesical electrical stimulation to assess increase in voided percentage during pressure-flow studies. Voided percentage is calculated as voided volume divided by the sum of voided volume and residual volume.
Change in Bothersome Symptoms and Sensation	baseline and post study procedures, up to 30 minutes	Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29) to assess whether electrical stimulation decreases urinary bothersome symptoms and increases bladder sensation during filling and emptying. Scores range from 0 (least severe) to 100 (most severe). Higher scores indicate greater severity of lower urinary tract symptoms.

Secondary Outcome Measures

Name	Time	Method
Bladder Contraction Strength	pressure-flow study, up to 30 minutes	Use of intraurethral electrical stimulation to assess contraction strength relative to baseline. Bladder pressure (cmH2O) is recorded over time during voiding.
Current Perception Threshold	CPT, up to 30 minutes	Assess bladder or urethral current perception threshold (CPT) in women with underactive bladder compared to normative values. The CPT value determined by the device is defined as the average of the minimum amplitude of the stimulus consistently detected and the stimulus 40 µA lower that was consistently not detected.
Cystometry Volume	cystometry, up to 30 minutes	Use of intravesical electrical stimulation to assess volumes at cystometric endpoints relative to baseline. Bladder sensation and urgency assessed at volume of first sensation during bladder filling, first desire to void, strong desire to void, and maximum cystometric capacity.
Bladder Contraction Duration	pressure-flow study, up to 30 minutes	Use of intraurethral electrical stimulation to assess contraction duration relative to baseline. Bladder pressure is recorded over time (seconds) during voiding.

Trial Locations

Locations (1)

Duke Medical Plaza Patterson Place; 🇺🇸 Durham, North Carolina, United States