Non-neurogenic urinary urge incontinence (UUI) is a common quality of life disorder that causes people to feel an "urgent" need to urinate. Standard treatment for UUI includes behavior modification, pelvic floor exercises, anticholinergic medication, and less commonly, sacral neuromodulation. Unfortunately anticholinergic therapy is only moderately effective. Botulinum toxin A (BTA or Botox©) may be a useful treatment in patients that do not respond to standard therapy. Botulinum toxin A has been used in other studies to improve symptoms in neurogenic urinary incontinence, and a variety of lower urinary tract disorders. BTA has been used in other studies to improve the symptoms in urinary incontinence, migraines, spinal cord injuries and a variety of lower urinary tract disorders. However, the treatment of non-neurogenic urinary urge incontinence has not been examined in a well-controlled study. The primary purpose of this study is to determine the efficacy of botulinum toxin A (BTA) in the treatment of non-neurogenic urinary urge incontinence (UUI). The secondary objectives are to examine the side effects associated with BTA treatment and the impact this treatment has on patients' quality of life.
Introduction: Non-neurogenic urinary urge incontinence (UUI) is a common quality of life disorder that becomes more prevalent with age. It is described as a condition that causes people to feel an "urgent" need to urinate due to muscle spasms in the bladder. Factors such as infection, inflammation, strokes, and dementia can stimulate the bladder to create spasms and cause urine loss. Overactive bladder refers to the symptom complex of urinary frequency, urgency and or nocturia with or without incontinence. Overactive bladder is a disorder of the storage phase of the bladder affecting approximately 16.9% of the US women, increasing to 31% after age 75. Standard treatment for UUI includes behavior modification, pelvic floor exercises, anticholinergic medication, and less commonly, sacral neuromodulation. Unfortunately anticholinergic therapy is only moderately effective and causes bothersome side effects, particularly at higher doses. Sacral neuromodulation therapy is currently unavailable in Saskatchewan with the closest treatment centre being located in Calgary. Botulinum toxin A (BTA or Botox©) may be a useful treatment in patients that do not respond to standard therapy. Botulinum toxin A has been used in other studies to improve symptoms in neurogenic urinary incontinence, migraines following spinal cord injuries, and a variety of lower urinary tract disorders. This product has been approved by FDA for treatments of the following conditions: two eye muscle disorders (blepharospasm and strabismus in December 1989), severe underarm sweating (primary axillary hyperhydrosis), brow furrow and frown lines (April 2002) and other cosmetic purposes (July 2004). For the treatment of UUI, BTA is injected into the detrusor muscle of the bladder which is the muscle of the bladder that squeezes urine towards the outlet. BTA has been used in other studies to improve the symptoms in urinary incontinence and a variety of lower urinary tract disorders, however, the treatment for non-neurogenic urinary urge incontinence has not been examined in a well-controlled study. Research Purpose and Objectives: The primary purpose of this study is to determine the efficacy of BTA in the treatment of non-neurogenic UUI. The secondary objectives are to examine the side effects associated with BTA treatment and the impact this treatment has on patients' quality of life. Research Methods: This study employs a 12 month, double-blinded, randomized, partial cross-over design. The first 6 months of the study, subjects will be randomized to receive either detrusor injection of BTA or a placebo injection. In the remaining six months, subjects in the control group will be offered the detrusor injection of BTA. All 36 subjects will be followed for the remaining 6 months. Study Procedures and Protocol Pre-injection Assessment: The pre-injection and assessment stage includes an evaluation of the medical history and physical exam. Previous therapy and medication will be disclosed to the physician. The investigator will ensure the subject meets the inclusion criteria, has had urinalysis and a pregnancy test if under 50 years old. Day of the Procedure: On the day of the surgery, the study pharmacist will randomize subjects using a random numbers table. The study doctor, nurses, and subjects will be blinded to treatment allocation. Ancef 1gm, or in the case of penicillin allergy, cipro 400 mg, will be given by intravenous. A local anaesthetic will be instilled at the end of the cystoscopy (40 ml 1% lidocaine) and sedation will be provided as required. Fifteen minutes will lapse before beginning the procedure. Using a 30 degree rigid scope and minimally invasive cystoscopic technique, 10 injections at 10 U/ml per injection (altogether 100 U of BTA) will be injected into the bladder wall, sparing the trigone.3,4 Subjects assigned to the placebo condition will receive injections of a saline at a similar frequency as the BTA injections. Subjects will be observed for 60 minutes post procedure and then discharged home. This is the standard protocol for other BTA procedures performed on an outpatient basis in the RQHR. Catheter supplies will be provided upon discharge. Follow-up Schedule: 1. Four to Six Weeks Post-Procedure: The primary and secondary measures will be assessed. 2. Three Months post-procedure: The same procedures will be repeated as at the four-to-six week assessment. 3. Six Months post-procedure: The four-to-six week assessment will be performed, and symptoms of retention or residual since the last visit will be discussed. A cystoscopy will be performed to study culture/urinalysis, measure desire and capacity, and show incontinence. Study allocation will be revealed at six months, and BTA injection will be offered to subjects that had received the placebo. 4. Nine Months: The four-to-six week procedures are repeated. 5. Twelve Months: The four-to-six week procedures are repeated. Potential Significance: Current anticholinergic therapy for non neurogenic UUI has limitations. In addition to significant systemic side effects, studies have shown that only 50% of patients improve with anticholinergic therapy, and that improvement does not always involve continence. Thus, detrusor injection of BTA may be a safe and efficacious therapy for patients who have failed standard therapy with anticholinergic medication and allow for an improved quality of life.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
21
Botulinum Toxins, Type A 100U injected into the detrusor at Day 1
Placebos injected into the detrusor at Day 1, followed by injection of botulinum toxin Type A 100U after 24 weeks has elapsed from previous treatment, if requested/qualified.
Regina General Hospital
Regina, Saskatchewan, Canada
Change in Maximum Capacity at Cystoscopy Between Baseline and 6 Month Follow-up
Cystoscopy is a test performed with a cystoscope, a narrow tube with a tiny camera at its tip, inserted into the urethra and bladder to see the inside of the bladder and urethra. Maximum bladder capacity--the amount of liquid or gas the bladder can hold under anesthesia. Without anesthesia, capacity is limited by either pain or a severe urge to urinate.
Time frame: Baseline to 6 months
Change in Incontinence Episodes Between Baseline and 6 Week Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline to 6 weeks
Change in Incontinence Episodes Between Baseline and 3 Month Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline to 3 month
Change in Incontinence Episodes Between Baseline and 6 Month Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline to 6 month
Change in Incontinence Episodes Between Baseline and 9 Month Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline to 9 months
Change in Incontinence Episodes Between Baseline and 12 Month Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline and 12 months
Change in Incontinence Episodes Between Baseline and 24 Months Follow-up
Incontinence- involuntary leakage of urine
Time frame: Baseline and 24 months
Change in Number of Daytime Voids Between Baseline and 6 Week Follow-up
Frequency of daily urination
Time frame: Baseline to 6 weeks
Change in Number of Daytime Voids Between Baseline and 3 Month Follow-up
Frequency of daily urination
Time frame: Baseline to 3 month
Change in Number of Daytime Voids Between Baseline and 6 Month Follow-up
Frequency of daily urination
Time frame: Baseline to 6 months
Change in Number of Daytime Voids Between Baseline and 9 Month Follow-up
Frequency of daily urination
Time frame: Baseline to 9 months
Change in Number of Daytime Voids Between Baseline and 12 Month Follow-up
Frequency of daily urination
Time frame: Baseline to 12 months
Change in Number of Daytime Voids Between Baseline and 24 Month Follow-up
Frequency of daily urination
Time frame: Baseline to 24 months
Change in Number of Night Voids Between Baseline and 6 Week Follow-up
Frequency of night voiding
Time frame: Baseline to 6 weeks
Change in Number of Night Voids Between Baseline and 3 Month Follow-up
Frequency of night voiding
Time frame: Baseline to 3 months
Change in Number of Night Voids Between Baseline and 6 Month Follow-up
Frequency of night voiding
Time frame: Baseline to 6 months
Change in Number of Night Voids Between Baseline and 9 Month Follow-up
Frequency of night voiding
Time frame: Baseline and 9 months
Change in Number of Night Voids Between Baseline and 12 Month Follow-up
Frequency of night voiding
Time frame: Baseline to 12 months
Change in Number of Night Voids Between Baseline and 24 Months Follow-up
Frequency of night voiding
Time frame: Baseline and 24 months
Subjective Benefit Assessment at 6 Weeks
Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: 1. dry (complete response), 2. improvement (\> 50% reduction in incontinence), 3. partial response (≤ 50% reduction in incontinence), 4. no response to treatment.
Time frame: Baseline to 6 weeks
Subjective Benefit Assessment at 3 Months
Self assessed description of how well they believed the Botulinum Toxin type A was working. The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: 1. dry (complete response), 2. improvement (\> 50% reduction in incontinence), 3. partial response (≤ 50% reduction in incontinence), 4. no response to treatment.
Time frame: Baseline to 3 months
Subjective Benefit Assessment at 6 Months
Self assessed description of how well they believed the Botulinum Toxin type A was working.The patients' subjective assessment of the treatment's efficacy was obtained verbally using a four-point rating scale. Rating options were: 1. dry (complete response), 2. improvement (\> 50% reduction in incontinence), 3. partial response (≤ 50% reduction in incontinence), 4. no response to treatment.
Time frame: Baseline to 6 months
Change in Incontinence Impact Questionnaire From Baseline to 6 Weeks Follow-up
Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 6 weeks
Change in Incontinence Impact Questionnaire From Baseline to 3 Months Follow-up
Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 3 months
Change in Incontinence Impact Questionnaire From Baseline to 6 Months Follow-up
Disease specific validated quality of life measure. Health-related quality of life measures for women with urinary incontinence. Incontinences Impact Questionnaire - 7 (IIQ-7) The IIQ-7 is 7-point scale used to rate a patients' life and the affect of accidental urine loss on activities, relationships, and feelings. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 6 months
Change in Urogenital Distress Inventory From Baseline to 6 Week Follow-up
Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. Urogenital Distress Inventory - 6 (UDI-6) The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 6 weeks
Change in Urogenital Distress Inventory From Baseline to 3 Months Follow-up
Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 3 months
Change in Urogenital Distress Inventory From Baseline to 6 Months Follow-up
Disease specific quality of life measure. Health-related quality of life measures for women with urinary incontinence. The UDI-6 is a 6-point scale that asks patients to respond to questions rating whether they experience and how much they are bothered by UUI. Item responses are assigned values of 0 for "not at all," 1 for "slightly," 2 for "moderately," and 3 for "greatly." The average score of items responded to is calculated. Higher scores reflect greater distress associated with symptoms. The average, which ranges from 0 to 3, is multiplied by 33 1/3 to put scores on a scale of 0 to 100.
Time frame: Baseline to 6 months
Change in Patient Perception of Bladder Condition From Baseline to 6 Weeks
Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time frame: Baseline to 6 weeks
Change in Patient Perception of Bladder Condition From Baseline to 3 Months
Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time frame: Baseline to 3 months
Change in Patient Perception of Bladder Condition From Baseline to 6 Months
Disease specific validated quality of life measures. A single-item global measure for patients with overactive bladder. Patient Perception of Bladder Condition (PPBC) The PPBC is a single-item, 6-point scale that asks patients to rate their subjective impression of their current bladder problems. It has been shown to have concurrent and discriminant validity as well as responsiveness to treatment. Patients are asked to rate their perceived bladder condition on a 6-point scale ranging from 1 "no problems at all", 2 "some very minor problems". 3 "some minor problems", 4"(some) moderate problems", 5 "severe problems", and 6 "many severe problems". A higher score indicates a more negative impression of current bladder problems.
Time frame: Baseline to 6 months
Change in Indevus Urgency Severity Scale From Baseline to 6 Weeks
A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time frame: Baseline to 6 weeks
Change in Indevus Urgency Severity Scale From Baseline to 3 Months
A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time frame: Baseline to 3 months
Change in Indevus Urgency Severity Scale From Baseline to 6 Months
A disease specific quality of life measure. A self reported measure that assesses urinary urgency severity associated with overactive bladder. Indevus Urgency Severity Scale (IIUS) The IIUS is a single item scale designed to describe urinary urges. The scale is rated through the patient's urge: none (0 points), mild (1), moderate (2) and severe (3). A higher score represents more urinary urges.
Time frame: Baseline to 6 months
24 Hour Pad Weight (gm) at 3 Months
weight of pad (in gm) worn for 24 hours to detect urine loss
Time frame: 3 months
24 Hour Pad Weight (gm) at 9 Months
weight of pad (in gm) worn for 24 hours to detect urine loss
Time frame: 9 months
Frequency of Urinary Tract Infections From Baseline to 6 Months
Frequency of urinary tract infections from baseline to 6 month-follow-up
Time frame: Baseline to 6 months
Frequency of Participants Needing Self-catheterization From Baseline to 6 Month Follow-up
Frequency of participants needing self-catheterization from baseline to 6 month follow-up.
Time frame: Baseline to 6 months
Frequency of Participants With Urinary Tract Infections From Baseline to 6 Months
Frequency of particiapnts with urinary tract infections from baseline to 6 month-follow-up
Time frame: Baseline to 6 months
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