- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01629433
Onabotulinumtoxina Intradetrusorial Injections and NGF Expression (Onab/A-NGF)
25. juni 2012 opdateret af: 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).
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
25
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Perugia, Italien, 06100
- University of Perugia, Dept. of Urology and Andrology
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 80 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
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.
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
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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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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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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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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. januar 2009
Primær færdiggørelse (Faktiske)
1. juni 2011
Studieafslutning (Faktiske)
1. marts 2012
Datoer for studieregistrering
Først indsendt
20. juni 2012
Først indsendt, der opfyldte QC-kriterier
25. juni 2012
Først opslået (Skøn)
27. juni 2012
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
27. juni 2012
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
25. juni 2012
Sidst verificeret
1. juni 2012
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- onabotulinumatoxin and NGF
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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