Safety and Effectiveness of a Non-invasive Neuromodulation Device on Urgency Urinary Incontinence in Overactive Bladder (Beacon)

Multi-center, Prospective, Randomized, Double-blind, Sham-controlled Clinical Study to Evaluate Safety and Effectiveness of a Transcutaneous, High-frequency, Amplitude-modulated, Non-invasive Neuromodulation Device on Urgency Urinary Incontinence in Subjects With Overactive Bladder (OAB)

The purpose of this study is to evaluate the change from baseline between the active and sham treatment groups in the treatment of urgency (urinary) incontinence episodes (leaks).

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Device: (VERV™ System); Device: Sham version of (VERV™ System)

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712-5803
      • Arizona Urologic Specialists
  • California
    • Murrieta, California, United States, 92562
      • Tri Valley Urology Medical Group
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GW Medical Faculty Associates
  • Florida
    • Naples, Florida, United States, 34102
      • Specialists in Urology
    • Pompano Beach, Florida, United States, 33060
      • Urology Center Of Florida
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Women's Health Institute of Illlinois, Ltd
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • 1st Urology, PSC dba Metropolitan Urology
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • New York
    • New York, New York, United States, 10016
      • University Urology Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • McKay Urology
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists, P.A.
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research
  • Washington
    • Mountlake Terrace, Washington, United States, 98043
      • Integrity Medical Research
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Wheaton Franciscan Medical Group - Milwaukee Urogynecology

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:

• Males and Females, at least 18 years of age
• Failure on primary OAB treatment, such as behavior modification or fluid/diet management, AND at least one (1) anti-cholinergic drug (unless patient was contra-indicated for anti-cholinergic use)
• Symptoms of overactive bladder for at least 6 months
• An average of one (1) or more urgency (urinary) incontinence episodes per 24-hours, over a 3-day period, confirmed by the 3-day baseline voiding diary, with a maximum of 12 urgency (urinary) incontinence episodes per 24-hours
• Dexterity and ability to place and operate the device
• Females of child-bearing capability agrees to use a reliable form of birth control for the duration of the trial
• An average of eight (8) or more voids per 24-hours, over a 3-day period, confirmed by the 3-day baseline voiding diary
• Willing and capable of understanding and complying with all requirements of the protocol, including proper completion of the baseline voiding diary
• Signed and dated the IRB-approved Informed Consent document.

Exclusion Criteria:

• Dysfunctional voiding symptoms unrelated to OAB, such as clinically significant bladder outlet obstruction, and urinary retention (pvr > 100 cc)
• Morbidly obese, defined as having Body Mass Index (BMI) > 40 kg/m2
• Stress predominant mixed urinary incontinence
• Neurological disease affecting urinary bladder function, including but not limited to Parkinson's disease, multiple sclerosis, stroke, spinal cord injury and uncontrolled epilepsy.
• Pelvic surgery (such as sub-urethral sling, pelvic floor repair) within the past 6 months
• Intravesical or urethral sphincter Botulinum Toxin Type A injections within the past 12 months
• Any neuromodulation therapy for overactive bladder within the past 3 months
• Failure to respond to previous neuromodulation therapy for overactive bladder
• Leading edge of any vaginal prolapse is beyond hymenel ring.
• Prior peri-urethral or transurethral bulking agent injections for bladder problems within the past 12 months.
• Any skin conditions affecting treatment or assessment of the treatment sites
• History of lower back surgery or injury that could impact placement of the patch, or where underlying scar tissue or nerve damage may impact treatment.
• Presence of an implanted electro-medical device (e.g. pacemaker, defibrillator, InterStim®, etc.), or any metallic implant in the lower back.
• Pregnant, nursing, suspected to be pregnant (by urine pregnancy method), or plans to become pregnant during the course of the study.
• Known latex allergies, or allergies or hypersensitivity to patch materials that will be in contact with the body (e.g., hydrogel, acrylic-based adhesive, polyurethane).
• Uncontrolled diabetes and/or diabetes with peripheral neuropathy.
• Current Urinary Tract Infection (UTI) or history of recurrent UTIs (>3 UTIs in the past year).
• History of lower tract genitourinary malignancies within the last 6 months or any previous pelvic radiation.
• Any clinically significant systemic disease or condition that in the opinion of the Investigator would make the patient unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active Treatment group; VERV™ System	Device: (VERV™ System); Active electrode patches are worn for 12 weeks, one per week. The patch is placed by the subject. All subjects will have access to active patches for 9 months after the sham-controlled 12-week portion of the study is complete.; Other Names: Non-invasive neurostimulation device
SHAM_COMPARATOR: Sham Treatment Group; Sham version of (VERV™ System)	Device: Sham version of (VERV™ System); Inactive (sham) electrode patches are worn for 12 weeks, one per week. The patch is placed by the subject. All subjects will have access to active patches for 9 months after the sham-controlled 12-week portion of the study is complete.; Other Names: Inactive Non-invasive neurostimulation device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Proportion of Responders Based on the Change From Baseline in Mean Urgency (Urinary) Incontinence Episodes (Leaks) Between the Active and Sham Treatment Groups	The primary objective of the randomized phase of the study is to evaluate the 12 week change from baseline in mean urgency (urinary) incontinence episodes (leaks) between the active and sham treatment groups. The mean of the number of urinary incontinence episodes over 24 hours" is defined as the mean of the number of UIEs recorded per 24 hour period for three consecutive days (via a 3-day diary). The primary objective of the open label phase of the study is to evaluate and confirm the continued efficacy of the VERV™ System for long-term use. The primary objective was assessed with rate of responders, where responder was defined as a subject who achieved a decrease of ≥50% in mean urgency urinary incontinence episodes at 12 weeks compared to baseline.	12 weeks (Randomized Phase) and 12 Months (Open Label)
Evaluate the Median Change From Baseline in Mean Urgency (Urinary) Incontinence Episodes (Leaks) Between the Active and Sham Treatment Groups	The primary objective of the randomized phase of the study is to evaluate the 12 week and 12 month median change from baseline in mean urgency (urinary) incontinence episodes (leaks) between treatment groups. The mean of the number of urinary incontinence episodes over 24 hours" is defined as the mean of the number of UIEs recorded per 24 hour period for three consecutive days (via a 3-day diary). Mean urinary frequency episodes calculated for each patient during time period. The median change in frequency was then calculated for each treatment group. Distribution of changes from baseline were then assessed prospectively for normality using the Kolmogorov - Smirnoff test. Since departure from normality was actually observed in the distribution, the Wilcoxon Rank-Sum test was performed to compare the median change between treatment groups and the p-values for the test of equality of medians were reported along with the medians.	12 weeks (Randomized Phase) and 12 Months (Open Label)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure Change in the Median of the Mean Urinary Frequency	Evaluate the 12 week change from baseline in median urinary frequency between the active and sham treatment groups. Mean urinary frequency episodes calculated for each patient during time period. The median change in frequency was then calculated for each treatment group. Distribution of changes from baseline were then assessed prospectively for normality using the Kolmogorov - Smirnoff test. Since departure from normality was actually observed in the distribution, the Wilcoxon Rank-Sum test was performed to compare the median change between treatment groups and the p-values for the test of equality of medians were reported along with the medians.	12 weeks and 12 Months
Measure Median Change in Mean Volume Per Void	Evaluate the 12 week median change from baseline in mean volume (ml) per void between the active and sham treatment groups	12 weeks
Measure Decrease in the Median Change From Baseline in Mean Urgency Episodes	Evaluate the 12 week change from baseline in median for mean number of urgency episodes between the active and sham treatment groups. Patients were required to complete seven 3-day voiding diaries throughout the course of the study. The voiding diary collected the following information: amount voided (in ml); urgency associated with each toileted void , approximate time of leak, and presence of urge preceding leak.The mean number of urgency episodes over 24 hours was then calculated for each patient during the observation period. The change in median for the mean of the number of urgency episodes over 24 hours) for each treatment group was then calculated. Distribution of changes from baseline were assessed prospectively using the Kolmogorov - Smirnoff test. The Wilcoxon Rank-Sum test was performed to compare the median change between treatment groups and the p-values for the test of equality of medians were reported along with the medians.	12 weeks
Measure Improvement in the Median of the Mean OAB-Symptom Composite Score	OAB Symptom Composite Score (OAB-SCS) is a composite symptom score of toilet voids, urgency severity and urge urinary incontinence combining the Indevus Urgency Severity Scale (IUSS) for capture of urgency severity per toilet void with 24-hour frequency and UUI episodes. IUSS Score/void and/or UUI is assigned an OAB-SCS Point/Void: 0(none)=1, 1(mild/easily tolerated)=2, 2(moderate discomfort interfering with activities)=3, 3(severe/extreme urgency discomfort that abruptly stopped all activity or tasks)=4, UUI without void=5. Overall OAB-SCS Score is calculated for each day by multiplying the OAB-SCS Points/Void and/or UUIs by the number of events meeting criteria and adding the individual scores together. The minimum overall OAB-SCS score in a 24 hour period would be a 1 (representing a single mild void with a OAB -SCS Point/Void score of 0). The score would increase based upon the number voids/events and overall severity each event. Medians calculated for each treatment group.	12 weeks
Change in Median Total Health Related Quality of Life (HRQL) of OAB-q From Baseline (Screening) to Week 12	The OAB-q is validated to measure symptom bother and life impact due to OAB. It consists of an 8-item Bother Scale to assess individual symptoms and a 25-item HRQL scale that in turn consists of 4 subscales (coping-8 items, concern-7 items, sleep-5 items and social-5 items) to assess impact on life. Responses for each item in the Bother Scale range from 1 (bothered not at all by the symptom) to 6 (Bothered A Very Great Deal). Scores are then added generating an overall Bother Score (severity) ranging from 8 to 48. For HRQL, individual responses range between 1-None of the Time to a 6-All of the Time. Subscale scores range from 8-48 (coping) 7-42 (concern), 5-30 (sleep) and 5-30 (social). Subscale scores are then added to generate the HRQL ranging between 25-150. Raw HRQL scores are transformed for standardization purposes as follows: ((Highest Possible Score-Actual Raw Score)/Range of Scores)*1 00 so that scores could range from 0 (All of the Time) to 100 (None of the Time).	12 Weeks (Randomized Phase) and 12 Months (Open Label).
Change in Patient Perception of Bladder Condition (PPBC) From Baseline (Screening Period) to Week 12 as Defined as an Improvement in Severity.	PPBC is a 6-point scale (from 'no problems at all' to 'many severe problems') describing the problem level of the bladder condition at that moment. Improvement is defined as a reduction in the number and/or severity of observed problems.	12 Weeks (Randomized Phase) and 12 Months (Open Label Phase)
Assessment of Treatment Benefit Scale (TBS)	TBS is a patient-reported outcome comprised of a 4-point scale of checkboxes to describe the change in condition during treatment (greatly improved to worsened). Improvement was defined as a change in the patient's assessment of overall condition to improved or greatly improved over the course of treatment. Analysis was based upon the number of patients who reported an improvement in condition.	12 Weeks
Assessment of Improvement as Measure by Overactive Bladder Satisfaction With Treatment Questionnaire (OAB-SAT)	Overall satisfaction with treatment was assessed (OAB-SAT-q) an 11 question list with multiple scaled checkboxes to allow the subject to rate the treatment with regard to satisfaction, bother from side effects, treatment endorsement, and convenience.	12 weeks
Change Clinical Global Impressions at 12 Weeks	CGI is an Investigator assessment, which rates the severity of illness at baseline on a scale of 1 (normal, not ill at all) to 7 (Amongst the most extremely ill patients), and then rates improvement at 12 weeks on a scale of 1 (very much improved) to 10 (very much worse). The analysis was based upon the number of patients that "much" and "very much" improved.	12 weeks (Randomized Phase) and 12 Months (Open Label Phase)

Collaborators and Investigators

• Sponsor: Ethicon Endo-Surgery
• Collaborators: Novella Clinical; Data & Inference, Inc.
• Investigators: Principal Investigator: Michael Kennelly, MD, McKay Urology

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (ESTIMATE): June 9, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 11, 2014
• Last Update Submitted That Met QC Criteria: September 4, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Overactive Bladder; Urinary Incontinence; Urgency; Frequency
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Urinary Bladder, Overactive; Urinary Incontinence; Enuresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: CI-10-0009