Clinical trial NCT01421719
Conditions: Parkinson's Disease Neurogenic Bladder Urinary Incontinence Clostridium Botulinum Toxin Adverse Reaction
Keywords: Parkinson's Disease Neurogenic Bladder Urinary Incontinence botulinum toxin cystoscopy Effect of Other Parasympatholytics [Anticholinergics and Antimuscarinics] and Spasmolytics
Sponsor: Stanford University
Start date: 2009-02-01; Completion date: 2011-07-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: botulinum toxin treatment Injection of Botox into urinary bladder for neurogenic symptoms.
Interventions: intervention 1: Cystoscopic injection of Botox into the urinary bladder
Intervention descriptions: intervention 1: 100 U of Botox A injected transurethrally into the urinary bladder muscle and submucosa.

Protocol documents: