Onabotulinumtoxina Intradetrusorial Injections and NGF Expression (Onab/A-NGF)
25. juni 2012 oppdatert av: 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).
Studieoversikt
Status
Fullført
Detaljert 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.
Studietype
Observasjonsmessig
Registrering (Faktiske)
25
Kontakter og plasseringer
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Studiesteder
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Perugia, Italia, 06100
- University of Perugia, Dept. of Urology and Andrology
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 80 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
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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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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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 |
Tiltaksbeskrivelse |
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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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Samarbeidspartnere og etterforskere
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Sponsor
Samarbeidspartnere
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. januar 2009
Primær fullføring (Faktiske)
1. juni 2011
Studiet fullført (Faktiske)
1. mars 2012
Datoer for studieregistrering
Først innsendt
20. juni 2012
Først innsendt som oppfylte QC-kriteriene
25. juni 2012
Først lagt ut (Anslag)
27. juni 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
27. juni 2012
Siste oppdatering sendt inn som oppfylte QC-kriteriene
25. juni 2012
Sist bekreftet
1. juni 2012
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- onabotulinumatoxin and NGF
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