Safety and Efficacy of botulinumA Toxin (BotoxA) for Treatment of Neurogenic Bladder of Parkinson's Disease
Condition: Parkinson's Disease; Neurogenic Bladder; Urinary Incontinence; Clostridium Botulinum Toxin Adverse Reaction
MeSH terms: Parkinson Disease; Urinary Bladder, Neurogenic; Urinary Incontinence; Enuresis
Study type: Interventional
Phase: Phase 4

Summary: 
      The basic nerve deficit of Parkinson's disease (PD) leads to lower urinary tract symptoms of
      frequency, urgency and urge urinary incontinence. Lower urinary tract symptoms tend to occur
      at more advanced stages of PD. In the over-65 year old age group, where 1% of men suffer from
      this disease, they are also prone to development of benign prostatic hyperplasia (BPH) and
      consequent associated lower urinary tract dysfunction. Similarly the over 65-year age group
      develop spontaneous overactive bladder up to a prevalence of 30% of both men and women. The
      urologic disorder is exceedingly devastating in reducing the quality of life in these
      individuals due to the lower urinary tract symptoms and ultimate urinary incontinence in a
      high proportion of patients.

      While attempts at pharmacologic treatment are partially satisfactory many patients are
      intolerant of oral drugs.

      Botulinum-A neurotoxin (BTX-A) has been shown in pilot trials to be quite effective in
      reducing overactive bladder symptoms and is specifically beneficial for a wide-variety of
      neurogenic bladder causes of over activity . The treatment procedure of injecting the
      detrusor muscle of the bladder with BTX-A is quite simple, does not impose significant risks
      to the patient, and can be performed as an office urologic procedure.

      This pilot clinical trial intends to demonstrate the safety and efficacy of low-dose Botox-A
      injections into the bladder to improve urinary symptoms in 20 patients.
    

Detailed description: 
      This open-label pilot study will evaluate the safety and efficacy of intra-detrusor
      injections of botulinum-A toxin (BTX-A) in 20 male or female patients with Parkinson's
      disease and neurogenic overactive bladder with or without urinary incontinence, but without
      evidence of significant urinary retention (>25% of bladder capacity at void).

      Patients will be invited to participate based upon subjective symptoms of uncontrolled lower
      urinary tract urgency, frequency and urinary incontinence. Only patients who have a Hoehn and
      Yahr Stage IV or better (or UPDRS equivalent) will be considered. Patients must have tried
      anti-muscarinic agents and failed to improve or were intolerant of these pharmacologic
      agents. Oral anti-muscarinic medications will be discontinued two weeks prior to urodynamics
      testing and treatment visit. At baseline urinary symptom scores will be obtained using The
      King's Health Questionnaire (KHQ, a validated scoring system for urinary symptoms) and the
      AUA Urinary Symptom Score. In addition a 3-day fluid intake and urinary outflow timed voiding
      diary will be submitted at the time of testing and treatment as well as follow-up visits.

      After signing an informed consent and meeting all inclusion and exclusion criteria, patients
      will be tested with urodynamic studies to determine current lower urinary tract
      neurophysiologic functioning. A "free-flow" urinary flow rate and post-void residual urine
      volume test will be performed as well as filling cystometrogram and pressure/flow
      measurement. Patients with evidence of outlet obstruction (high pressure/low flow) will be
      excluded from the study. Only patients with a post-void residual urine volume less than or
      equal to 25% of the total bladder volume at void will be included. No catheters or other
      measurement devices will be attached to the body at the time of the initial free urinary flow
      and post-void urine volume measurement. A repeat pressure/flow determination will be
      performed during the urodynamics cystometrogram.

      After qualification to proceed, patients will then be transferred to the adjoining cystoscopy
      suite. Pre-procedure oral sedation and analgesia will be given. Subjects will undergo
      cystoscopy under topical lidocaine anesthesia and undergo 25-gauge needle injections of
      BTX-A. BTX-A treatment for each participant will be limited to a total dose of 100 units in a
      minimum of 10 to 20 locations. Any patient unable to void after the procedure will receive an
      indwelling catheter for 24 hours. Patients will be contacted by telephone within 24-48 hours
      after the procedure for safety assessment. Follow-up clinic visit evaluations will occur at 1
      month, 3 months, 6 months and 9 months. A 3-day voiding diary, King's Health Questionnaire,
      AUA Symptom Score sheet and Global Response Assessment (GRA) Questionnaire will be collected
      at each follow-up visit. Incontinence will be documented on this diary. Uroflowmetry and
      post-void residual volume will also be assessed at each follow-up visit.
    

Intervention name(s): Cystoscopic injection of Botox into the urinary bladder
Intervention type(s): Drug
Intervention description(s): 100 U of Botox A injected transurethrally into the urinary bladder muscle and submucosa.
Other intervention name(s): Botox A (Allergan, Inc)
Intervention MeSH terms: Botulinum Toxins, Type A
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Parkinson's Disease; Neurogenic Bladder; Urinary Incontinence; botulinum toxin; cystoscopy; Effect of Other Parasympatholytics [Anticholinergics and Antimuscarinics] and Spasmolytics