Onabotulinumtoxina Intradetrusorial Injections and NGF Expression (Onab/A-NGF)
25 juin 2012 mis à jour par: Antonella Giannantoni, University Of Perugia
PHASE IV STUDY ON THE EFFECTS OF ONABOTULINUMTOXINA INTRADETRUSORIAL INJECTIONS ON BLADDER EXPRESSION OF NGF, TRKA, P75 AND TRPV1 IN PATIENTS WITH DETRUSOR OVERACTIVITY
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).
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
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.
Type d'étude
Observationnel
Inscription (Réel)
25
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Perugia, Italie, 06100
- University of Perugia, Dept. of Urology and Andrology
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 80 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
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.
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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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.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
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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.
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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.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
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To evaluate urodynamic improvements
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Improvement in uninhibited detrusor contractions' maximum pressure (cmh20).
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To investigate urodynamic improvements.
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Improvement in uninhibited detrusor contractions' first volume (ml)
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To investigate urodynamic improvements.
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Improvement in maximum cystometric capacity (ml).
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 janvier 2009
Achèvement primaire (Réel)
1 juin 2011
Achèvement de l'étude (Réel)
1 mars 2012
Dates d'inscription aux études
Première soumission
20 juin 2012
Première soumission répondant aux critères de contrôle qualité
25 juin 2012
Première publication (Estimation)
27 juin 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
27 juin 2012
Dernière mise à jour soumise répondant aux critères de contrôle qualité
25 juin 2012
Dernière vérification
1 juin 2012
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- onabotulinumatoxin and NGF
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