Efficacy of Botulinum Toxin Type A for the Treatment of Non-neurogenic Urinary Urge Incontinence
Condition: Urinary Urge Incontinence
MeSH terms: Urinary Incontinence, Urge
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Botulinum Toxins, Type A; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Urinary incontinence, urge; detrusor hyperreflexia; detrusor instability; non-neurogenic; Female Urogenital Diseases and Pregnancy Complications; Female Urogenital Diseases; Urologic Diseases; Urination Disorders; Urinary Incontinence