Clinical Feasibility Study, Implantable Tibial Nerve Stimulator (ITNS)

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.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Device: Implantation and neuromodulation therapy

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Ramon, California, United States, 94583
      • Pacific Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DEVICE_FEASIBILITY
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Study device; 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; 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.; 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

Collaborators and Investigators

• Sponsor: Nine Continents Medical, Inc.
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Parminder Sethi, M.D., Pacific Urology

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 9, 2019
• Primary Completion (ACTUAL): January 31, 2021
• Study Completion (ACTUAL): March 3, 2021

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (ACTUAL): October 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive
• Other Study ID Numbers: ITNS-01; R44DK121578 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes