Onabotulinumtoxina Intradetrusorial Injections and NGF Expression

Overactive Detrusor Clinical Trial

— Onab/A-NGF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01629433
• Other study ID #: onabotulinumatoxin and NGF
• Status: Completed
• Phase: Phase 4
• First received: June 20, 2012
• Last updated: June 25, 2012
• Start date: January 2009
• Est. completion date: March 2012

Study information

• Verified date: June 2012
• Source: University Of Perugia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Observational

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Patients affected by refractory overactive bladder (OAB) symptoms and detrusor overactivity (idiopathic and neurogenic DO) refractory to conventional anticholinergics (at least 3 antimuscarinic agents -- tolterodine, oxybutynin and solifenacin -- each taken for at least 1 month).

Exclusion Criteria:

• OAB symptoms due to bladder outlet obstruction because of urogenital prolapse in females and benign prostatic hyperplasia in males,

• recurrent urinary tract infections,

• cognitive impairment,

• pregnancy,

• anticoagulant therapy,

• psychoactive agents modulating bladder function (venlafaxine, amitriptyline), aminoglycosides, and other drugs thought to interfere with bladder function

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Detrusor Hyperreflexia of Bladder
• Overactive Detrusor
• Urinary Bladder, Overactive

Locations

Country	Name	City	State
Italy	University of Perugia, Dept. of Urology and Andrology	Perugia

Sponsors (2)

Lead Sponsor	Collaborator
University Of Perugia	Allergan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.		No
Secondary	To evaluate urodynamic improvements	Improvement in uninhibited detrusor contractions' maximum pressure (cmh20).		No
Secondary	To investigate urodynamic improvements.	Improvement in uninhibited detrusor contractions' first volume (ml)		No
Secondary	To investigate urodynamic improvements.	Improvement in maximum cystometric capacity (ml).		No