Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome

• Total frequency within 3 days from baseline to 1 month after the treatment day [ Time Frame: one month after initial treatment ] [ Designated as safety issue: Yes ]

  Efficacy:

  Net change of the total frequency within 3 days from baseline to 1 month after the treatment day based on the record of the 3-day voiding diary

  Safety:

  1. Local adverse event incidences (hematuria, miction pain, urinary tract infection, urinary retention)
  2. Systemic adverse events.
  
  

• Voiding and urodynamic parameters [ Time Frame: One month after the initial treatment day ] [ Designated as safety issue: Yes ]

  Efficacy:(measured the net change of variables from baseline to 1 month)

  1. Urgency episodes/3 days
  2. Urgency urinary incontinence (UUI)/3 days
  3. Overactive bladder symptom score (OABSS)
  4. Urgency severity score (USS)
  5. Functional bladder capacity (FBC)
  6. Maximum flow rate (Qmax)
  7. Postvoid residual volume (PVR)
  8. Global response assessment (GRA) of satisfaction by the patient
  9. Urodynamic parameters from baseline to 3 months

  Safety:

  1. Local adverse event incidences (hematuria, miction pain, urinary tract infection, urinary retention)
  2. Systemic adverse events.
  
  

Overactive bladder (OAB) is a symptom syndrome characterized by urgency frequency with or without urgency incontinence, usually no metabolic or anatomical disorders can be found and it may have great impact on quality of life. Traditional medication for OAB is antimuscarinic agent which targets at the muscarinic receptors. There are several adverse events such as dry mouth, constipation, blurred vision, and dizziness related to antimuscarinics, therefore, some patients cannot tolerated this treatment. Intravesical botulinum toxin A (BoNT-A) has recently emerged as novel treatment for OAB refractory to antimuscarinics, however, BoNT-A injection can cause acute urinary retention and large postvoid residual. Urinary tract infection usually occurred following large postvoid residual and urinary retention. If we can deliver BoNT-A through the urothelium to the suburothelial space, but not into the detrusor layer, we might have therapeutic effects on the urothelial sensory nerves without compromising the detrusor contractility. This treatment will enable us to prevent the undesired detrusor underactivity after BoNT-A injection, especially in the elderly patients who had impaired detrusor contractility and OAB. Liposomes are vesicles, composed of concentric phospholipid bilayers separated by aqueous compartments. Because liposomes adsorb to cell surfaces and fuse with cells, they are being used as vehicles for drug delivery and gene therapy. In this grant we will evaluate liquid liposome delivery of BoNT-A (Liposome encapsulated BoNT-A) into the bladder without the need for cystoscopic-guided needle injection for refractory OAB, and study the mechanism of action of intravesical liposomal drug delivery. If successful, we will leverage our technology transfer expertise and bring the science from the bench top to the bed side to apply for a physician sponsored Investigational New Drug (IND) trial using liposome-BoNT in patients with OAB or DO.