Onabotulinumtoxina Intradetrusorial Injections and NGF Expression

NCT01629433 | Completed DMC

• 1 other identifier: onabotulinumatoxin and NGF
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Overactive Detrusor; Detrusor Hyperreflexia of Bladder

Keywords

idiopathic detrusor overactivity; neurogenic dysfunction; onabotulinumtoxinA

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (3)

• To evaluate urodynamic improvements

• To investigate urodynamic improvements.

• To investigate urodynamic improvements.

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University Of Perugia: lead
• Allergan: collaborator

Study Sites (1)

University of Perugia, Dept. of Urology and Andrology

Perugia, Italy, 06100, Italy

Location

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.

MeSH Terms

Conditions

Urinary Bladder, Overactive

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR OF UROLOGY

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: June 27, 2012
• Study Start: January 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: March 1, 2012
• Last Updated: June 27, 2012

Record last verified: 2012-06

Locations

IT (1)