Clinical trial NCT05241379: AURA-2: Augmenting Urinary Reflex Activity
Official title: Exploratory Safety and Electrophysiological Study of Closed-loop Pudendal Neuromodulation Using an Implantable (Picostim-DyNeuMo) Device in Women With Urinary Incontinence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overactive Bladder
Urge Incontinence
Lead sponsor: Amber Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2022-02-15
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: AMBER AURA-2 study (Augmenting Urinary Reflex Activity 2) is a short-duration (6 month) safety and electrophysiological study using an implanted Amber UI system and two electrode leads to provide closed-loop pudendal nerve stimulation for the treatment of urinary incontinence.


Eligibility criteria: Inclusion Criteria:

* Female patients aged ≥ 18 years
* Diagnosis of urinary incontinence, with on a 5-day voiding diary at least 1 daily urgency episode and/or greater than or equal to 8 voids/day and/or by having a minimum of two involuntary leaking episodes in 72 hr
* Duration of urinary incontinence symptom ≥ 6 months prior to the screening baseline visit date
* Failed or is not a candidate for more conservative treatment e.g. pelvic floor muscle therapy or biofeedback or behavioral modification
* Failed or could not tolerate at least one (1) antimuscarinic or beta3-adrenoceptor agonist medication
* Urodynamic testing (uroflowmetry, cystometry and pressure flow) completed within 12 months prior to screening baseline visit date or is willing to have testing at screening baseline visit
* Cystoscopy test completed within 12 months prior to the screening baseline visit date or is willing to have a test at screening baseline visit
* Is willing and able to washout from OAB medications for at least 4 week prior to beginning the baseline voiding diary
* Ability and willingness to give informed consent including language constraints (see above)
* Able to participate in all testing and follow-up clinic visits associated with study protocol
* Capable of independently using the system components (after training) as described in the Patient Manual
* Mobile and able to use toilet without assistance

Exclusion Criteria:

General:

* Patient is pregnant, breastfeeding, or plans to become pregnant during the course of the study (pregnancy tests provided in schedule)
* Patient is unwilling or unable to use contraception during sexual intercourse for the duration of the study, and thereafter if implant remains in the longer term.
* Any significant medical condition that is likely to interfere with study procedures, device operation, or likely to confound evaluation of study endpoints
* Any psychiatric or personality disorder at the discretion of the study physician
* Any neurological condition that may interfere with normal bladder function (e.g., stroke, multiple sclerosis, Parkinson's disease; clinically significant peripheral neuropathy, or complete spinal cord injury)
* Patient has uncontrolled type I or type II diabetes as defined by their routine care clinician or diabetes with peripheral nerve involvement
* Any history of any pelvic cancer
* Patient has history of other non-pelvic neoplasia within 5 years prior to enrolment, except for a cancer that was determined to be local occurrence only, such as basal cell carcinoma, or is receiving or planning to receive anti-cancer or anti-angiogenic drugs
* Patient has proven major autoimmune disease, e.g. scleroderma or immunodeficiency (including use of biologic immunomodulatory drugs at time of procedure)
* Life expectancy of less than 1 year
* Patient is a frail elderly and/or with notable clinical evidence of sarcopaenia
* Patient is not suitable for the study as determined by their routine care physician for any other reason
* Patient is enrolled in another interventional study excepting observational studies, e.g. SNM registries or in relation to disease (see below)
* Patient participation in vigorous sporting activities where these cannot be restricted for a period of 6 weeks post-implantation.

Specific urological

* Urinary tract mechanical obstruction such as urethral stricture
* Current symptomatic urinary tract infection (UTI) or more than 3 UTIs in past year
* Pure stress incontinence or mixed incontinence where the stress component overrides the urge component
* Interstitial cystitis or bladder pain syndrome as defined by either AUA or EAU guidelines
* Suspected pudendal nerve entrapment syndrome. In patients with co-existent symptoms of chronic pelvic pain and urinary incontinence, Nantes criteria will be used for screening. Patients meeting essential criteria will be excluded from the study
* Treatment of urinary symptoms with botulinum toxin therapy in the past 12 months
* Prior attempt at pudendal nerve stimulation using an implanted lead
* Treatment of urinary symptoms with tibial or sacral nerve stimulation in the past 3 months (prior experience of either before this time is permitted provided no implants remain in-situ)

Specific technical

* Patient is significantly obese (defined as BMI ≥ 35) so as to limit electrode lead placement using standard approaches
* Skin, orthopaedic or neurological anatomical limitations that could prevent successful placement of the electrode lead
* Knowledge of planned MRIs, diathermy, microwave exposure, high output ultrasonic exposure, or RF energy exposure
* Implantable neurostimulator, pacemaker or defibrillator in situ (anywhere in body including sacral and tibial)
* Subject with a documented history of allergic response to titanium, zirconia, polyurethane, epoxy, or silicone

Primary outcomes:
measure: Adverse Device Events
timeFrame: 24 hours; 1 week; 4 weeks; 3 months; 6 months
Secondary outcomes:
measure: Changes in Voiding diary data
timeFrame: Baseline, 28 days, 3 months, 6 months
measure: Changes in ICIQ -UI Short Form
timeFrame: Baseline, 28 days, 3 months, 6 months
measure: Changes in ICIQ-OAB Quality of Life
timeFrame: Baseline, 28 days, 3 months, 6 months
measure: Changes in PGI-I
timeFrame: Baseline, 28 days, 3 months, 6 months
measure: Changes in FSFI
timeFrame: Baseline, 28 days, 3 months, 6 months
measure: Technical Outcomes
timeFrame: 24 hours postoperatively
measure: Measurement of EMG
timeFrame: During procedure, 24 hours and 6 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
Study officials:
References: