Clinical Feasibility Study, Implantable Tibial Nerve Stimulator (ITNS)

Study Overview
=================
Brief Summary
-----------------
Study objectives: To report feasibility data for safety and effectiveness of the study device. Study device: Nine Continents Medical implantable tibial nerve stimulator (ITNS) model 9C-680 with programmer model 9C-580. Intended use: The study device is intended for treatment of the symptoms of overactive bladder (OAB), including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatments. Type of design: Single-arm longitudinal design. Study sites: Single site, in the United States. Study duration: One year total, comprising six months for enrolling and implanting 10 subjects, and 26 weeks for follow-up.

Official Title
-----------------
Clinical Feasibility Study, Implantable Tibial Nerve Stimulator (ITNS)

Conditions
-----------------
Overactive Bladder

Intervention / Treatment
-----------------
* Device: Implantation and neuromodulation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At pre-screening: Age 18 years or older; Documented diagnosis of overactive bladder; Documented failed behavioral intervention and/or physical therapy; Documented failed first drug for overactive bladder; and Documented failed second drug for overactive bladder. At screening: Life expectancy of at least one year; Capable of tolerating the implantation procedure; Ambulatory and able to use the toilet independently and without difficulty; and Able to sense and tolerate posterior tibial nerve stimulation (transcutaneous test). Based on pre-therapy voiding diary: Average daily voids during waking hours ≥ 11; Average daily voids interrupting sleep ≥ 2.0; Average daily voids associated with urgency ≥ 4; or Average daily incontinence episodes ≥ 1. Exclusion Criteria: At pre-screening: Predominant stress incontinence; For females, pelvic organ prolapse quantification (POP-Q) ≥ grade II; Neurologic disease, e.g. MS, Parkinson's; Abnormal upper urinary tract function; Neurogenic bladder; Bladder stone or tumor; Body mass index (BMI) > 40; Chronic pelvic pain; Urinary fistula; Peripheral neuropathy; History of failed neuromodulation for overactive bladder; Uncontrolled bleeding disorder; End stage renal failure, glomerular filtration rate (GFR) < 35, or dialysis; Untreated diabetes or A1C > 7; Implanted pacemaker, defibrillator, or neurostimulator; History of pelvic cancer within the past two years; Condition requiring magnetic resonance imaging (MRI); Condition requiring diathermy; Metallic implant in planned site of study device; For females, pregnant; For females, planning to become pregnant; For females, given birth in the last 6 months; or For females, of child-bearing potential and not willing to practice a medically-approved method of birth control during the study. At screening: Anatomical restriction preventing device placement; Skin lesions or compromised skin at the implant site; For females, pelvic organ prolapse quantification (POP-Q) ≥ grade II; Post-void residual > 150 cc; Urinary tract mechanical obstruction due to urethral stricture; Urinary tract mechanical obstruction due to bladder neck contracture; In males, urinary tract mechanical obstruction due to benign prostatic hyperplasia (BPH); Vesicoureteral reflux; Cystoscopic abnormalities that could be malignant; Current cystitis; Current urethritis; Gross hematuria; In females, positive pregnancy test; Any other medical condition with potential effect on bladder function, as assessed by investigator; or Any other medical condition that could compromise the safety of the subject, as assessed by investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study device<br>Subjects who provide informed consent, meet all inclusion criteria, and no exclusion criterion, will have a study device implanted and followed closely for 26 weeks. | Device: Implantation and neuromodulation therapy<br>* The study device is an autonomous permanent implant for neuromodulation targeting the posterior tibial nerve. It does not require an external power source or charger.<br>* Other names: Nine Continents Medical ITNS model 9C-680;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Urinary Incontinence Frequency From Baseline to 13 Weeks | For a participant analyzed, let x0 = average number of voids with leakage per 24 hours in first 72 hours of baseline diary, x1 = average number of voids with leakage per 24 hours in first 72 hours of 13-week diary, and x = percent change of urinary incontinence frequency from baseline to 13 weeks. Then x = 100 * (x1 - x0) / x0. For example, a participant with an average of 4 voids with leakage per 24 hours in the first 72 hours of the baseline diary and 2 voids with leakage per 24 hours in the first 72 hours of the 13-week diary would have a percent change of urinary incontinence frequency from baseline to 13 weeks of 100 * (2 - 4) / 4 = -50. | Baseline to 13 weeks | 
| Percent Change of Excess Voiding Frequency During Waking Hours From Baseline to 13 Weeks | For a participant analyzed, let x0 = average number of voids during waking hours per 24 hours in first 72 hours of baseline diary, x1 = average number of voids during waking hours per 24 hours in first 72 hours of 13-week diary, and x = percent change of excess voiding frequency during waking hours from baseline to 13 weeks, where excess means voids during waking hours exceeding 7 per 24 hours. Then x = 100 * (x1 - x0) / (x0 - 7). For example, a participant with an average of 16 voids during waking hours per 24 hours in the first 72 hours of the baseline diary and an average of 10 voids during waking hours per 24 hours during the first 72 hours of the 13-week diary would have a percent change of excess voiding frequency during waking hours from baseline to 13 weeks of 100 * (10 - 16) / (16 - 7) = -67. | Baseline to 13 weeks | 
| Percent Change of Frequency of Voids Awakening From Sleep From Baseline to 13 Weeks | For a participant analyzed, let x0 = average number of voids awakening from sleep per 24 hours in first 72 hours of baseline diary, x1 = average number of voids awakening from sleep per 24 hours in first 72 hours of 13-week diary, and x = percent change of frequency of voids awakening from sleep from baseline to 13 weeks. Then x = 100 * (x1 - x0) / x0. For example, a participant with an average of 2 voids awakening from sleep per 24 hours in the first 72 hours of the baseline diary and an average of 1 void awakening from sleep per 24 hours during the first 72 hours of the 13-week diary would have a percent change of frequency of voids awakening from sleep from baseline to 13 weeks of 100 * (1 - 2) / 2 = -50. | Baseline to 13 weeks | 
| Percent Change of Frequency of Voids With Urgency From Baseline to 13 Weeks | For a participant analyzed, let x0 = average number of voids with urgency per 24 hours in first 72 hours of baseline diary, x1 = average number of voids with urgency per 24 hours in first 72 hours of 13-week diary, and x = percent change of frequency of voids with urgency from baseline to 13 weeks, where voids with urgency means voids self-reported with some or severe urgency, or leakage. Then x = 100 * (x1 - x0) / x0. For example, a participant with an average of 8 voids with urgency per 24 hours in the first 72 hours of the baseline diary and an average of 5 voids with urgency per 24 hours during the first 72 hours of the 13-week diary would have a percent change of frequency of voids with urgency from baseline to 13 weeks of 100 * (5 - 8) / 8 = -37.5 | Baseline to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Threshold at 13 Weeks | Neuromodulation pulse amplitude required to evoke paresthesia or motor response (threshold) at 13 weeks. | 13 weeks | 
| Change of Score on an Overactive Bladder Questionnaire Short-form (OAB-q SF) Symptom Bother Subscale From Baseline to 13 Weeks | The overactive bladder questionnaire short-form (OAB-q SF) symptom bother subscale ranges from 0 to 100, and higher symptom bother scores indicate greater symptom bother ( worse outcome). For a participant analyzed, let x0 = symptom bother score at baseline, x1 = symptom bother score at 13 weeks, and x = x0 - x1. For example, a participant with a symptom bother score of 60 at baseline and a symptom bother score of 20 at 13 weeks would have a change of score on the overactive bladder questionnaire short-form (OAB-q SF) symptom bother subscale from baseline to 13 weeks of -40. | Baseline to 13 weeks | 
| Score on a Global Response Assessment (GRA) Scale at 13 Weeks | The global response assessment (GRA) scale ranges from 1 to 6, with 1 corresponding to markedly worse and 6 corresponding to markedly better, so that higher scores represent better outcomes.. | 13 weeks |