Onabotulinumtoxina Intradetrusorial Injections and NGF Expression (Onab/A-NGF)
In the last years, botulinum toxin type A (onab/A) has been increasingly used as a treatment option for overactive bladder symptoms in patients affected by either neurogenic and idiopathic detrusor overactivity (DO). How onab/A injected into the detrusor muscle improves overactive bladder symptoms in neurologic patients has been only partially investigated.Some evidence suggested that the neurotoxin probably reduces detrusor muscle contraction blocking detrusor muscle cholinergic innervation. However, recent experimental observations indicated that onab/A determines more complex effects on bladder activity acting on afferent innervations as well as on the efferent one. Only few experimental studies have investigated the activity of onab/A on bladder afferent nervous transmission. Experimental studies in animals showed that Nerve Growth Factor (NGF) elicits increased sensation, urgency and DO. Although there are some evidence on the ability of onab/A to improve DO and to reduce bladder and urinary content of NGF, how onab/A influences NGF expression and the expression of TrKa, p75 and TRPV1 receptors is still unclear. The hypothesis is that onab/A reduces NGF bladder tissue levels and in the same time it modulates the gene expression of NGF associated receptors (TrkA, p75 and TRPV1).
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||PHASE IV STUDY ON THE EFFECTS OF ONABOTULINUMTOXINA INTRADETRUSORIAL INJECTIONS ON BLADDER EXPRESSION OF NGF, TRKA, P75 AND TRPV1 IN PATIENTS WITH DETRUSOR OVERACTIVITY|
- to investigate onab/A- induced changes on gene expression of NGF, TRPV1, TrkA and p75 in bladder wall tissue of patients with neurogenic and idiopathic DO. [ Designated as safety issue: No ]All patients underwent cystoscopy with bladder wall biopsy specimens. After undergoing cystoscopy with bladder sampling patients underwent onab/A intradetrusorial injections. Patients were injected with 100 or 300 onab/A U according to the type of DO. Urodynamic studies and cystoscopies with bladder sampling were repeated 1 month later. NGF and neuroreceptors (TrkA, TRPV1, p75)gene expression have been measured with Real Time Polymerase Chain reaction. NGF bladder tissue content (protein) has been added into evaluation and measured with ELISA.
- To evaluate urodynamic improvements [ Designated as safety issue: No ]Improvement in uninhibited detrusor contractions' maximum pressure (cmh20).
- To investigate urodynamic improvements. [ Designated as safety issue: No ]Improvement in uninhibited detrusor contractions' first volume (ml)
- To investigate urodynamic improvements. [ Designated as safety issue: No ]Improvement in maximum cystometric capacity (ml).
Biospecimen Retention: Samples With DNA
Bladder biopsy specimens obtained from the postero-lateral wall of the bladder with cold cup resection. Deep bladder wall biopsy including urothelium and smooth muscle were performed. No biopsies were taken from the bladder neck or the trigone.
|Study Start Date:||January 2009|
|Study Completion Date:||March 2012|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
botulinum A toxin
18 patients with neurogenic DO and 7 with idiopathic DO All the patients had overactive bladder (OAB) symptoms and DO refractory to conventional anticholinergics.
NGF has been suggested to modulate neurotransmitters' release, induces synaptic reorganization and influences neuronal excitability acting on Trk/A and p75 associated receptors. Moreover, recent observations indicated that NGF-induced DO and noxious input depend on the interaction of NGF with TRPV1, that is over-expressed in overactive bladders and interstitial cystitis/painful bladder syndrome. From a clinical point of view, a decrease in urinary NGF levels has been detected in patients with DO treated with onab/A. Although there are some evidence on the ability of onab/A to improve DO and to reduce bladder and urinary content of NGF, how onab/A influences NGF expression and the expression of TrKa, p75 and TRPV1 receptors is still unclear.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01629433
|University of Perugia, Dept. of Urology and Andrology|
|Perugia, Italy, 06100|