Pilot Study of Liposome-encapsulated OnabotulinumtoxinA for Patients with Overactive Bladder: A Single-center Study

Background: Intradetrusor onabotulinumtoxinA (BoNT-A) injection benefits overactive bladder (OAB) patients, but increased postvoid residual (PVR) urine volume and urinary tract infection (UTI) remain risks. Intravesical instillation of liposomal BoNT-A instead of injection could prevent such adverse events. Objective: To evaluate instillation of liquid liposomal BoNT-A (Lipotoxin) for the treatment of OAB and to determine its mechanism of action. Design, setting, and participants: A double-blind randomized parallel controlled pilot trial in 24 OAB patients at a single tertiary center. Intervention: Patients were randomly assigned to intravesical instillation of Lipotoxin containing 80 mg liposomes and 200 U BoNT-A or normal saline (N/S). Patients were retreated with Lipotoxin 1 mo later if they failed the first treatment. Outcome measurement and statistical analysis: Voiding diaries, OAB symptom scores, urodynamic studies, and adverse events were monitored. The primary end point was change of total urinary frequency per 3 d at 1 mo after treatment. Immunohistochemistry and Western blotting for synaptic vesicle glycoprotein 2A (SV2A) and synaptosomal-associated protein, 25 kDa (SNAP25) were performed at baseline and 3 mo after treatment. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. Results and limitations: At 1 mo after treatment, the change of urinary frequency per 3 d significantly improved in the Lipotoxin group (n = 12; median: -6.50; interquartile range [IQR]: -18.3 to -0.25; p = 0.008) but not in the N/S group. (n = 12.0; IQR: -7.75 to 8.0; p = 0.792). Urgency episodes also showed a significant decrease in the Lipotoxin group (-12.0; IQR: -20.3 to -2.75; p = 0.012) but not in the N/S group (-1.0; IQR: -11.0 to 2.5; p = 0.196). SV2A and SNAP25 were expressed in urothelial cells and suburothelial tissues. However, the protein expression did not significantly differ between responders and nonresponders at 3 mo after treatment. Conclusions: Intravesical Lipotoxin instillation effectively reduced frequency episodes 1 mo after treatment in OAB patients without any increase in PVR or risk of UTI. Patient summary: We demonstrated that intravesical Lipotoxin instillation reduced frequency episodes at 1 mo in overactive bladder patients. This procedure is safe, without an increase in postvoid residual or the risk of urinary tract infection. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.