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-ONA 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 80mg 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.
Written by:
Kuo HC, Liu HT, Chuang YC, Birder LA, Chancellor MB. Are you the author?
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan; Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Departments of Medicine and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Oakland University, William Beaumont School of Medicine, Royal Oak, MI, USA.
Reference: Eur Urol. 2014 Feb 11. pii: S0302-2838(14)00115-8.
doi: 10.1016/j.eururo.2014.01.036
PubMed Abstract
PMID: 24555904
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