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临床试验/NCT01629433
NCT01629433已完成不适用

PHASE IV STUDY ON THE EFFECTS OF ONABOTULINUMTOXINA INTRADETRUSORIAL INJECTIONS ON BLADDER EXPRESSION OF NGF, TRKA, P75 AND TRPV1 IN PATIENTS WITH DETRUSOR OVERACTIVITY

University Of Perugia1 个研究点 分布在 1 个国家目标入组 25 人开始时间: 2009年1月最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
25
试验地点
1
主要终点
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.

研究概览

简要总结

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).

详细描述

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.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
18 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者
否

入选标准

  • •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).

排除标准

  • •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

结局指标

主要结局

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.

次要结局

  • To investigate urodynamic improvements.
  • To evaluate urodynamic improvements

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Antonella Giannantoni

ASSOCIATE PROFESSOR OF UROLOGY

University Of Perugia

研究点 (1)

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