AURA-2: Augmenting Urinary Reflex Activity

Exploratory Safety and Electrophysiological Study of Closed-loop Pudendal Neuromodulation Using an Implantable (Picostim-DyNeuMo) Device in Women With Urinary Incontinence

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.

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