A Prospective, Multicenter, Double-Blind, Randomized Trial of Bladder Instillation of Liposome Formulation OnabotulinumtoxinA for Interstitial Cystitis/Bladder Pain Syndrome

Abstract

Purpose: Intravesical instillation of liposomal formulated botulinum toxin A (lipotoxin) has shown therapeutic effects as treatment of refractory overactive bladder without needle injections. We assessed lipotoxin to treat refractory interstitial cystitis/bladder pain syndrome.

Materials and methods: This 2-center, double-blind, randomized, placebo controlled, physician initiated study enrolled patients with refractory interstitial cystitis/bladder pain syndrome. A total of 31 patients were assigned to intravesical instillation of lipotoxin (onabotulinumtoxinA 200 U with 80 mg sphingomyelin), 28 were assigned to onabotulinumtoxinA 200 U in normal saline and 31 were assigned to normal saline alone. The primary end point was the average change in O'Leary-Sant symptom scores, including ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index) between baseline and 4 weeks after treatment. Other end points included the average changes in a 3-day voiding diary, a visual analog scale for pain and a global response assessment of patient satisfaction.

Results: Improvements in the pain scale and O'Leary-Sant symptom scores occurred in all 3 groups by 4 weeks after treatment. Lipotoxin instillation was associated with a statistically significant decrease in O'Leary-Sant symptom scores (mean ± SD 7.38 ± 8.75), ICSI (4.00 ± 4.28), ICPI (3.35 ± 5.11) and the visual analog scale pain scale (1.64 ± 2.52), and an increase in the global response assessment (1.35 ± 1.28). However, there was no difference in improvement among the 3 groups. No significant adverse events were found in any group.

Conclusions: Lipotoxin failed to demonstrate a positive proof of concept compared to onabotulinumtoxinA or placebo. However, a single intravesical instillation of lipotoxin was associated with decreased interstitial cystitis/bladder pain syndrome symptoms compared to baseline in patients with moderate to severe interstitial cystitis/bladder pain syndrome. The effect was likely due to a significant placebo effect.

Keywords: botulinum toxin; interstitial cystitis; liposome; pelvic pain; urinary bladder.