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

Overactive Bladder Clinical Trial

— Beacon  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01369485
• Other study ID #: CI-10-0009
• Status: Completed
• Phase: N/A
• First received: May 24, 2011
• Last updated: September 4, 2014
• Start date: June 2011
• Est. completion date: December 2013

Study information

• Verified date: September 2014
• Source: Ethicon Endo-Surgery
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: December 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Overactive Bladder
• Urinary Bladder, Overactive
• Urinary Incontinence

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	McKay Urology	Charlotte	North Carolina
United States	Alliance Urology Specialists, P.A.	Greensboro	North Carolina
United States	1st Urology, PSC dba Metropolitan Urology	Jeffersonville	Indiana
United States	Integrity Medical Research	Mountlake Terrace	Washington
United States	Tri Valley Urology Medical Group	Murrieta	California
United States	Carolina Urologic Research	Myrtle Beach	South Carolina
United States	Specialists in Urology	Naples	Florida
United States	University Urology Associates	New York	New York
United States	Women's Health Institute of Illlinois, Ltd	Oak Lawn	Illinois
United States	Urology Center of Florida	Pompano Beach	Florida
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Arizona Urologic Specialists	Tucson	Arizona
United States	GW Medical Faculty Associates	Washington	District of Columbia
United States	Wheaton Franciscan Medical Group - Milwaukee Urogynecology	Wauwatosa	Wisconsin

Sponsors (3)

Lead Sponsor	Collaborator
Ethicon Endo-Surgery	Data & Inference, Inc., Novella Clinical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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).	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No