Clinical trial NCT04000763: Superficial Peroneal Nerve Neuromodulation for Non-Obstructive Urinary Retention
Official title: Superficial Peroneal Nerve Neuromodulation for Non-Obstructive Urinary Retention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Retention
Urinary Bladder, Underactive
Keywords: Bladder
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction
name: University of North Carolina, Chapel Hill
First posted: 2019-06-27
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All experiments proposed in this grant application will be performed in female non-obstructive urinary retention patients. We chose not to study male patients in this study given the need to exclude bladder outlet obstruction from benign prostatic hyperplasia (BPH), an evaluation that is invasive and costly.
Primary purpose: BASIC_SCIENCE

Brief summary: Millions of Americans are suffering from underactive bladder (UAB). The impact of severe UAB, i.e. non-obstructive urinary retention (NOUR) on quality of life is significant because current treatment for non-obstructive urinary retention requires intermittent self-catheterization or an indwelling suprapubic catheter. Currently an effective drug for non-obstructive urinary retention does not exist. It is a therapeutic challenge for clinicians to successfully treat non-obstructive urinary retention. Sacral neuromodulation has been approved by the FDA since 1999 to treat non-obstructive urinary retention. It achieves \>50% improvement in bladder emptying (reducing the frequency of self-catheterization or increasing voided volume) in just over half of the patients. Sacral neuromodulation requires surgical implantation of a stimulator and a lead with 4 electrodes. The surgery and implant are invasive and expensive, preventing a broad application of this effective therapy to many non-obstructive urinary retention patients. The goal of this study is to develop a novel non-invasive neuromodulation therapy for non-obstructive urinary retention as an alternative. Specifically, the investigators will explore the possibility to translate into humans a recent discovery in cats of an excitatory reflex from the superficial peroneal nerve to the bladder to treat non-obstructive urinary retention. Therefore, in this study the investigators propose to develop a non-invasive, transcutaneous neuromodulation therapy for non-obstructive urinary retention that can be administered at home.

Detailed description: Hypothesis: Electrical stimulation of the superficial peroneal nerve using transcutaneous skin electrodes attached on the dorsal foot can treat non-obstructive urinary retention either by enhancing bladder sensation thereby reducing bladder volume needed for initiating voiding and/or by enhancing bladder contraction, thereby increasing voiding efficiency and reducing post-void residual (PVR) volume.

Rationale: The investigators conducted preliminary studies in cats that have demonstrated an excitatory reflex to the bladder elicited by stimulation of afferent axons in the superficial peroneal nerve. Activating this excitatory reflex in cats reduced bladder capacity (the minimal volume for initiating a micturition reflex), enhanced bladder contractions and overcame bladder inhibition emanating from somatic (tibial) afferent activation. Since the superficial peroneal nerve innervates the dorsal skin of the foot in humans, it can be stimulated non-invasively by skin surface electrodes. Transcutaneous stimulation of this nerve, should it prove efficacious, would likely be more acceptable to patients with non-obstructive urinary retention (NOUR) than invasive sacral neuromodulation therapy. Therefore, in this study, the investigators propose to test the superficial peroneal nerve neuromodulation in non-obstructive urinary retention patients.

Specific Aim: Determine the efficacy of superficial peroneal nerve stimulation (SPNS) in the treatment of patients with non-obstructive urinary retention using skin electrodes attached to the dorsal surface of the foot.

Rationale: Based on a preliminary discovery in cats, the investigators propose to further investigate the effect of superficial peroneal nerve stimulation (SPNS) on voiding efficiency, post-void residual (PVR) volume, and bladder capacity (voided volume + post-void residual) in patients with non-obstructive urinary retention. A reduced bladder capacity indicates more normal bladder filling sensations, thereby allowing voiding at more normal volumes. The investigators plan to test superficial peroneal nerve stimulation in 10 non-obstructive urinary retention patients by collecting voiding diary during a 3-week period. Baseline voiding diary will be collected during the first week before superficial peroneal nerve stimulation initiation. During the second week, superficial peroneal nerve stimulation will be administered to each patient for 3 hours/day before sleep and it will also be administered immediately prior and throughout each void. The 3-hour stimulation is designed to modulate bladder sensory pathways to enhance bladder sensation, thereby reducing the bladder volume required to initiate voiding. The acute stimulation during each void is designed to enhance bladder contraction, thereby increasing voiding efficiency and reducing post-void residual. During the third week, superficial peroneal nerve stimulation will not be applied, and a voiding diary will be collected to determine any post-stimulation effect. Since the superficial peroneal nerve is a cutaneous nerve innervating the skin of the dorsal foot, superficial peroneal nerve stimulation will be applied non-invasively by attaching skin surface electrodes to the dorsal side of the foot.

Eligibility criteria: Inclusion Criteria:

Able to provide informed consent

1. 18 years of age and older
2. Clinically diagnoses as non-obstructive urinary retention
3. Post Void Residual of 300 mL or greater
4. Currently using daily self-catheterization to empty the bladder
5. Capable of using the toilet independently without difficulty
6. Capable and willing to follow all study-related procedures

Exclusion Criteria:

1. Neurologic diagnosis (including diabetes mellitus)
2. Surgery within one year of screening for urinary outlet obstruction
3. Pregnant or planning to become pregnant during study duration
4. OnabotulinumtoxiA use in bladder or pelvic floor muscles with the past year
5. Pacemaker or implantable defibrillator
6. Current Urinary tract or vaginal infections
7. Current Interstim use
8. Current Percutaneous tibial nerve stimulation (PTNS) or transcutaneous electrical nerve stimulation (TENS) use in pelvis or back or legs
9. Investigational drug/ device therapy with the past 4 weeks,
10. Participation in any clinical investigation involving or impacting gynecologic or urinary function with the past 4 weeks,
11. Previous surgery of or damage to the foot or nerves in the foot and leg.

Primary outcomes:
measure: Number of voids per subject in 24 hours.
timeFrame: 3 weeks
measure: Number of catheterizations per subject in 24 hours.
timeFrame: 3 weeks
measure: Volume of urine per void.
timeFrame: 3 weeks
measure: Catheterized Post Void Residual volume
timeFrame: 3 weeks
measure: Bladder Voiding efficiency
timeFrame: 3 weeks
measure: Bladder capacity
timeFrame: 3 weeks
Secondary outcomes:
measure: Efficacy of Foot Stimulation
timeFrame: 2 weeks
measure: Efficacy of Foot Stimulation
timeFrame: 3 weeks
measure: Post-stimulation effect
timeFrame: 1 week
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Urology
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Christopher Chermansky, MD
role: STUDY_DIRECTOR
References:
citation: 26872574
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