Onabotulinumtoxina Intradetrusorial Injections and NGF Expression (Onab/A-NGF)

This study has been completed.

Sponsor:

Collaborator:

Allergan

Information provided by (Responsible Party):

Antonella Giannantoni, University Of Perugia

ClinicalTrials.gov Identifier:

NCT01629433

First received: June 20, 2012

Last updated: June 25, 2012

Last verified: June 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	June 20, 2012
Last Updated Date	June 25, 2012
Start Date ^ICMJE	January 2009
Primary Completion Date	June 2011 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: June 25, 2012)	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.
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01629433 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: June 25, 2012)	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).
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	Onabotulinumtoxina Intradetrusorial Injections and NGF Expression
Official Title ^ICMJE	PHASE IV STUDY ON THE EFFECTS OF ONABOTULINUMTOXINA INTRADETRUSORIAL INJECTIONS ON BLADDER EXPRESSION OF NGF, TRKA, P75 AND TRPV1 IN PATIENTS WITH DETRUSOR OVERACTIVITY
Brief 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).
Detailed 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.
Study Type ^ICMJE	Observational
Study Design ^ICMJE	Observational Model: Cohort Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	Retention: Samples With DNA Description: 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.
Sampling Method	Non-Probability Sample
Study Population	We consecutively enrolled 18 patients with neurogenic DO (8 patients with spinal cord injury: 7 men and 1 women, mean age: 46±2 yrs, disease duration 6.25±1 yrs; 10 patients with suprapontine bilateral lesions: 4 men and 6 women, mean age: 55±4 yrs, disease duration 6.6±1.49 yrs ) and 7 with idiopathic DO (3 men and 4 female, mean age: 53±5 yrs, disease duration 7.1±1.53 yrs). All the patients had overactive bladder (OAB) symptoms and DO refractory to conventional anticholinergics (at least 3 antimuscarinic agents -- tolterodine, oxybutynin and solifenacin -- each taken for at least 1 month). Anticholinergics were discontinued one month before entry into the study.
Condition ^ICMJE	Overactive Detrusor Detrusor Hyperreflexia of Bladder
Intervention ^ICMJE	Not Provided
Study Group/Cohort (s)	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.
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	25
Completion Date	March 2012
Primary Completion Date	June 2011 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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
Gender	Both
Ages	18 Years to 80 Years
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Italy

Administrative Information
NCT Number ^ICMJE	NCT01629433
Other Study ID Numbers ^ICMJE	onabotulinumatoxin and NGF
Has Data Monitoring Committee	Yes
Responsible Party	Antonella Giannantoni, University Of Perugia
Study Sponsor ^ICMJE	University Of Perugia
Collaborators ^ICMJE	Allergan
Investigators ^ICMJE	Not Provided
Information Provided By	University Of Perugia
Verification Date	June 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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