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

This study has been completed.
Sponsor:
Collaborators:
Novella Clinical, Inc.
Data & Inference, Inc.
Information provided by (Responsible Party):
Ethicon Endo-Surgery
ClinicalTrials.gov Identifier:
NCT01369485
First received: May 24, 2011
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention
Overactive Bladder
Device: (VERV™ System)
Device: Sham version of (VERV™ System)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Ethicon Endo-Surgery:

Primary Outcome Measures:
  • Evaluate Proportion of Responders Based on the Change From Baseline in Mean Urgency (Urinary) Incontinence Episodes (Leaks) Between the Active and Sham Treatment Groups [ Time Frame: 12 weeks (Randomized Phase) and 12 Months (Open Label) ] [ Designated as safety issue: No ]

    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.


  • Evaluate the Median Change From Baseline in Mean Urgency (Urinary) Incontinence Episodes (Leaks) Between the Active and Sham Treatment Groups [ Time Frame: 12 weeks (Randomized Phase) and 12 Months (Open Label) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Measure Change in the Median of the Mean Urinary Frequency [ Time Frame: 12 weeks and 12 Months ] [ Designated as safety issue: No ]

    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.


  • Measure Median Change in Mean Volume Per Void [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Evaluate the 12 week median change from baseline in mean volume (ml) per void between the active and sham treatment groups

  • Measure Decrease in the Median Change From Baseline in Mean Urgency Episodes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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.


  • Measure Improvement in the Median of the Mean OAB-Symptom Composite Score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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.


  • Change in Median Total Health Related Quality of Life (HRQL) of OAB-q From Baseline (Screening) to Week 12 [ Time Frame: 12 Weeks (Randomized Phase) and 12 Months (Open Label). ] [ Designated as safety issue: No ]
    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).

  • Change in Patient Perception of Bladder Condition (PPBC) From Baseline (Screening Period) to Week 12 as Defined as an Improvement in Severity. [ Time Frame: 12 Weeks (Randomized Phase) and 12 Months (Open Label Phase) ] [ Designated as safety issue: No ]
    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.

  • Assessment of Treatment Benefit Scale (TBS) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    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.

  • Assessment of Improvement as Measure by Overactive Bladder Satisfaction With Treatment Questionnaire (OAB-SAT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Change Clinical Global Impressions at 12 Weeks [ Time Frame: 12 weeks (Randomized Phase) and 12 Months (Open Label Phase) ] [ Designated as safety issue: No ]
    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.


Enrollment: 163
Study Start Date: June 2011
Study Completion Date: December 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Inactive Non-invasive neurostimulation device

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369485

Locations
United States, Arizona
Arizona Urologic Specialists
Tucson, Arizona, United States, 85712-5803
United States, California
Tri Valley Urology Medical Group
Murrieta, California, United States, 92562
United States, District of Columbia
GW Medical Faculty Associates
Washington, District of Columbia, United States, 20037
United States, Florida
Specialists in Urology
Naples, Florida, United States, 34102
Urology Center of Florida
Pompano Beach, Florida, United States, 33060
United States, Illinois
Women's Health Institute of Illlinois, Ltd
Oak Lawn, Illinois, United States, 60453
United States, Indiana
1st Urology, PSC dba Metropolitan Urology
Jeffersonville, Indiana, United States, 47130
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, New York
University Urology Associates
New York, New York, United States, 10016
United States, North Carolina
McKay Urology
Charlotte, North Carolina, United States, 28207
Alliance Urology Specialists, P.A.
Greensboro, North Carolina, United States, 27403
United States, South Carolina
Carolina Urologic Research
Myrtle Beach, South Carolina, United States, 29572
United States, Washington
Integrity Medical Research
Mountlake Terrace, Washington, United States, 98043
United States, Wisconsin
Wheaton Franciscan Medical Group - Milwaukee Urogynecology
Wauwatosa, Wisconsin, United States, 53226
Sponsors and Collaborators
Ethicon Endo-Surgery
Novella Clinical, Inc.
Data & Inference, Inc.
Investigators
Principal Investigator: Michael Kennelly, MD McKay Urology
  More Information

No publications provided

Responsible Party: Ethicon Endo-Surgery
ClinicalTrials.gov Identifier: NCT01369485     History of Changes
Other Study ID Numbers: CI-10-0009
Study First Received: May 24, 2011
Results First Received: April 14, 2014
Last Updated: September 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Ethicon Endo-Surgery:
Urinary Incontinence
Overactive Bladder
Frequency
Urgency

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Incontinence
Lower Urinary Tract Symptoms
Signs and Symptoms
Urinary Bladder Diseases
Urination Disorders
Urologic Diseases
Urological Manifestations

ClinicalTrials.gov processed this record on October 23, 2014