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
  Purpose

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).


Condition Phase
Overactive Detrusor
Detrusor Hyperreflexia of Bladder
Phase 4

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by University Of Perugia:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 25
Study Start Date: January 2009
Study Completion Date: March 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01629433

Locations
Italy
University of Perugia, Dept. of Urology and Andrology
Perugia, Italy, 06100
Sponsors and Collaborators
University Of Perugia
Allergan
  More Information

No publications provided

Responsible Party: Antonella Giannantoni, ASSOCIATE PROFESSOR OF UROLOGY, University Of Perugia
ClinicalTrials.gov Identifier: NCT01629433     History of Changes
Other Study ID Numbers: onabotulinumatoxin and NGF
Study First Received: June 20, 2012
Last Updated: June 25, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Of Perugia:
idiopathic detrusor overactivity
neurogenic dysfunction
onabotulinumtoxinA

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Botulinum Toxins, Type A
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014