Clinical trial NCT02577302: CAN-Stim Compared to SNS in Treatment of Urinary Urgency Incontinence With Wireless Neuromodulation Technology
Official title: Multi-center, Prospective, Randomized, Controlled, Non-Inferiority, Clinical Trial of Chronic Afferent Nerve Stimulation (CAN-Stim) of the Tibial Nerve Versus Sacral Nerve Stimulation (SNS) in the Treatment of Urinary Urgency Incontinence Resulting From Refractory Overactive Bladder (OAB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Urinary Incontinence, Urge
Keywords: Chronic Tibial nerve stimulation
Wireless PNS
neuromodulation
Lead sponsor: Uro Medical Corporation
Sponsor class: INDUSTRY
First posted: 2015-10-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, Randomized, Controlled, Non-Inferiority
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, controlled, multi-center, study in which 150 evaluable subjects will be randomized 1:1 to receive either a Protect CAN-Stim or SNS InterStim® system. Subjects from both groups will immediately start with therapy. The primary endpoint is a ≥ 50% reduction in number of incontinence episodes associated with urgency at the 3-month visit, with additional measurements assessed at 14 days, 1, 6, 9 and 12-months.

Detailed description: Subjects will be randomized at baseline to either CAN-Stim or SNS InterStim® after inclusion and exclusion criteria have been met, 150 subjects will be randomized in to either arm of the study (89 subjects each arm).

At the following visit, CAN-Stim subjects will be immediately implanted unilaterally with a permanent device (implantation side up to investigators discretion). During implantation, the subject should feel pulsation in their foot with or without toe flexion, confirming stimulation of the tibial nerve. Subjects not achieving this motor response will not have the device implanted and will be exited from the study. Implanted subjects will be educated on the use of the transmitter and programmer. Programming parameters will be set and therapy will be delivered for a minimum of 8 hours per day for 2 weeks. Programming changes can be done as needed during this time period to maximize clinical response. At the 2-week visit, diaries will be reviewed and confirmed for accuracy and discrepancies and the number of urgency incontinence episodes will be calculated and compared to baseline diaries. Subjects who are considered a responder at the 2-week follow-up visit (\>50% improvement in urgency related incontinence episodes) will continue therapy and followed for a total of 12 months with primary outcomes assessed at 3 months. Non-responders will be offered an explant of the device and will exit the study. Subjects having less than 50% improvement may choose to keep the device. These subjects will be followed for adverse events with phone calls at 3, 6 and 12 months.

Subjects randomized to SNS will have their Stage I device implanted and tested during a 2-week period. Stage I will have a tined, quadripolar lead placed in the S3 (preferred) or S4 (alternate) foramen in the standard fashion using fluoroscopic guidance and motor response. Motor responses can include a contraction of the levators ("bellows" response) with or without plantar flexion of the great toe. Subjects who are not demonstrating an appropriate motor response will not have the device implanted and will be exited from the study. Subjects, who respond intraoperatively, will have the extension lead connected and externalized in the standard fashion. Subjects may have their InterStim® activated 24 hours/day, but a minimum of 8 hours per day for 2 weeks is required to remain in the study. Programming changes can be done as needed during this time period to maximize the clinical effect. At the 2-week visit, diaries will be reviewed and confirmed for accuracy and clarified for discrepancies and the number of urgency incontinence episodes will be calculated and compared to baseline diaries. Patients achieving a clinical response (\>50% improvement in urgency related incontinence episodes) will undergo implantation of a pulse generator and removal of the percutaneous extension lead. The IPG will be programmed in the standard fashion using settings that were working for the patient during the 2-week trial. Subjects implanted with the InterStim® device will be monitored for a total of 12 months with primary outcomes assessed at 3 months. Non-responders will be offered an explant of the device and will exit the study. Subjects having less than 50% improvement may choose to keep the device. These subjects will be followed for adverse events with phone calls at 3, 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of overactive bladder with urgency urinary incontinence or mixed incontinence (urge and stress) with predominate urge, as confirmed by the MESA questionnaire;
* Women and men ≥ 18 years of age;
* Women of child-bearing age willing to practice birth control;
* At least 4 incontinent episodes associated with urgency on a 3-day voiding diary;
* At least 10 voids per day;
* Average urgency score of at least 2 as measured with IUSS on a 3-day voiding diary;
* Self-reported bladder symptoms present \> 6 months;
* Documented failure of an adequate trial of first and second line therapy;
* Off all antimuscarinics and beta-3 adrenergic agonists for at least 2 weeks prior to enrollment;
* If on Tricyclic antidepressants, dosage must be stabilized for at least 3 months;
* Have no active urethral obstruction/stricture, bladder calculi or bladder tumor based on medical history;
* Normal upper urinary tract function based on medical history;
* Based on the medical opinion of the Investigator, there is no evidence of anatomic abnormalities that could jeopardize the placement of the device or pose a hazard to the subject;
* Based on the medical opinion of the Investigator, subject is willing and able to operate the patient programmer, recharging equipment, diary and has the ability to undergo study assessments and provide accurate responses;
* Based on the medical opinion of the Investigator, subject is a good surgical subject for the implant procedure;
* Capable of giving informed consent;
* Capable and willing to follow all study related procedures.

Exclusion Criteria:

* An active implantable electronic device regardless of whether stimulation is ON or OFF;
* Pregnant as confirmed by a urine pregnancy test or plan to become pregnant during the following 12 months period;
* Primary complaint of stress urinary incontinence;
* Less than 1 year post-partum and/or are breast-feeding;
* Neurogenic bladder (i.e. Multiple sclerosis, Parkinson's, Spinal Cord Injury);
* Patients with spinal hardware that would limit access to the sacrum;
* Botox use in bladder or pelvic floor muscles in the past nine months;
* Have a post-void residual urine volume \>150 cc at baseline;
* Current urinary tract infection (UTI);
* Previous treatment with sacral neuromodulation;
* Previous treatment with percutaneous tibial nerve stimulation, pelvic floor muscle stimulation, or biofeedback within the past 60 days;
* Conditions requiring Magnetic Resonance Imaging (MRI) evaluation or diathermy procedures;
* Inability to operate the CAN-Stim System or InterStim System;
* Diabetes with peripheral nerve compromise or severe uncontrolled diabetes (HbA1C 8.5 or greater);
* History of coagulopathy or bleeding disorder;
* History of pelvic pain as primary diagnosis (VAS score of \> 4) at baseline;
* Anatomical restrictions such that device placement is not possible;
* Are currently participating or have participated within the past 30 days in any clinical investigation involving or impacting urinary or renal function;
* Have a life expectancy of less than 1 year;
* Cannot independently comprehend and complete the questionnaires and diaries;
* Deemed unsuitable for enrollment by the investigator based on history or physical examination (including bleeding disorders or anticoagulant medications, and peripheral neuropathy);
* Dependent on wearable, transcutaneous, or other therapeutic medical device (examples: glucose monitor, TENS) for treatment of a disease or disorder.

Primary outcomes:
measure: Response rate: a ≥ 50% reduction in number of urgency related incontinence episodes
timeFrame: 3 Months
measure: device- and procedure-related Adverse Events (AE)
timeFrame: 3 Months
Secondary outcomes:
measure: Response rate: a ≥ 50% reduction in number of urgency related incontinence episodes
timeFrame: 6,12 Months
measure: device- and procedure-related Adverse Events (AE)
timeFrame: 6,12 Months
measure: Voiding Frequency
timeFrame: 3, 6,12 Months
measure: Reduction in degree of urgency
timeFrame: 3, 6,12 Months
Other outcomes:
measure: Quality of Life: I-QOL: Quality of Life Scale (I-QOL)
timeFrame: 3, 6,12 Months
measure: Proportion of subjects dry
timeFrame: 3, 6,12 Months
measure: Episodes
timeFrame: 3, 6,12 Months
measure: Improvement
timeFrame: 3, 6,12 Months
measure: OAB
timeFrame: 3, 6,12 Months
measure: AE's
timeFrame: 6, 12 months
Locations:
city: Laguna Hills
country: United States
facility: Tilda Research Inc
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Placentia
country: United States
facility: Westview Clinical Research
state: California
city: Daytona Beach
country: United States
facility: Advanced Urology Institute
state: Florida
city: Miami
country: United States
facility: Baptist Health Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Florida Urology Partners
state: Florida
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Pain Consultants
state: Missouri
city: Omaha
country: United States
facility: Adult & Pediatric Urology, P.C.
state: Nebraska
city: New York
country: United States
facility: Urology - Iris Cantor Men's Health Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Columbus
country: United States
facility: Integrated Pain Specialists
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma health Sciences Center
state: Oklahoma
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
References: