Clinical trial NCT04516434: Amplifying Sensation in Underactive Bladder
Official title: AMPLIFY: Amplifying Sensation in Underactive Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Bladder, Underactive
Keywords: electrical stimulation
urodynamics
bladder
urethra
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-08-18
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Voided Percentage
timeFrame: pressure-flow study, up to 30 minutes
measure: Change in Bothersome Symptoms and Sensation
timeFrame: baseline and post study procedures, up to 30 minutes
Secondary outcomes:
measure: Current Perception Threshold
timeFrame: CPT, up to 30 minutes
measure: Cystometry Volume
timeFrame: cystometry, up to 30 minutes
measure: Bladder Contraction Strength
timeFrame: pressure-flow study, up to 30 minutes
measure: Bladder Contraction Duration
timeFrame: pressure-flow study, up to 30 minutes
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Medical Plaza Patterson Place
state: North Carolina
Study officials:
affiliation: Duke University
name: Cindy L Amundsen, MD
role: STUDY_CHAIR
affiliation: Duke University
name: Em Abbott, PhD
role: PRINCIPAL_INVESTIGATOR
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