Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome
19 de setembro de 2014 atualizado por: Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital
Comparative Study of the Efficacy and Safety of Liposome Encapsulated Botulinum Toxin-A (Lipotoxin) Versus Normal Saline Instillation in Treatment of Patients With Refractory Overactive Bladder Syndrome
Overactive bladder (OAB) is a bothered symptom syndrome.
Traditional medication for OAB is antimuscarinic agent.
However, adverse events such as dry mouth, constipation, blurred vision, and dizziness may prohibit patient to take this drug for OAB.
Intravesical botulinum toxin A (BoNT-A) is a novel treatment however, BoNT-A can cause acute urinary retention and large postvoid residual.
In this grant we will evaluate liquid liposome delivery of BoNT-A (Liposome encapsulated BoNT-A) into the bladder without the need for cystoscopic-guided needle injection for refractory OAB.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
Overactive bladder (OAB) is a symptom syndrome characterized by urgency frequency with or without urgency incontinence, usually no metabolic or anatomical disorders can be found and it may have great impact on quality of life.
Traditional medication for OAB is antimuscarinic agent which targets at the muscarinic receptors.
There are several adverse events such as dry mouth, constipation, blurred vision, and dizziness related to antimuscarinics, therefore, some patients cannot tolerated this treatment.
Intravesical botulinum toxin A (BoNT-A) has recently emerged as novel treatment for OAB refractory to antimuscarinics, however, BoNT-A injection can cause acute urinary retention and large postvoid residual.
Urinary tract infection usually occurred following large postvoid residual and urinary retention.
If we can deliver BoNT-A through the urothelium to the suburothelial space, but not into the detrusor layer, we might have therapeutic effects on the urothelial sensory nerves without compromising the detrusor contractility.
This treatment will enable us to prevent the undesired detrusor underactivity after BoNT-A injection, especially in the elderly patients who had impaired detrusor contractility and OAB.
Liposomes are vesicles, composed of concentric phospholipid bilayers separated by aqueous compartments.
Because liposomes adsorb to cell surfaces and fuse with cells, they are being used as vehicles for drug delivery and gene therapy.
In this grant we will evaluate liquid liposome delivery of BoNT-A (Liposome encapsulated BoNT-A) into the bladder without the need for cystoscopic-guided needle injection for refractory OAB, and study the mechanism of action of intravesical liposomal drug delivery.
If successful, we will leverage our technology transfer expertise and bring the science from the bench top to the bed side to apply for a physician sponsored Investigational New Drug (IND) trial using liposome-BoNT in patients with OAB or DO.
Tipo de estudo
Intervencional
Inscrição (Real)
62
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Hualien, Taiwan, 970
- Buddhist Tzu Chi General Hospital
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Adults with age of 20 years old or above
- Patients with symptoms of urgency frequency and/or urge incontinence and a urgency severity scale (USS) of at least 2, with or without urodynamically proven detrusor overactivity (DO) (defined by the International Continence Society (ICS) recommendation as: spontaneous detrusor contraction occurring during bladder filling phase or occurring before uninhibited detrusor contraction voiding at bladder capacity in the urodynamic study)
- Free of active urinary tract infection
- Free of bladder outlet obstruction on enrollment
- Free of overt neurogenic bladder dysfunction
- Having been treated with antimuscarinic agents for at least 4 weeks without effect or with intolerable adverse effects
- Patient has not been treated with bladder surgery for OAB, such as enterocystoplasty, that might affect the therapeutic effect of test drug
- Patient can record voiding diary for the urinary frequency and urgency
- Patient or his/her legally acceptable representative has signed the written informed consent form
Exclusion Criteria:
- Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms
- Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
- Patients with bladder outlet obstruction on enrollment
- Patients with postvoid residual >150 mL
- Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
Patients have laboratory abnormalities at screening including:
Alanine aminotransferase (ALT) >3 x upper limit of normal range Aspartate aminotransferase (AST) >3 x upper limit of normal range Patients have abnormal serum creatinine level >2 x upper limit of normal range
- Patients with any contraindication to be urethral catheterization during treatment
- Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
- Myasthenia gravis, Eaton Lambert syndrome.
- Patients with any other serious disease considered by the investigator not suitable for general anesthesia or in the condition to enter the trial
- Patients participated investigational drug trial within 1 month before entering this study
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Experimental arm
Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL in Liposome 80 mg/40 mL) in single intravesical instillation Liposome encapsulated botulinum toxin A' |
Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL water in Liposome 80 mg/40 mL water) in single intravesical instillation, one time treatment at the treatment day
Outros nomes:
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Comparador de Placebo: Control arm
Normal saline 50 mL in single intravesical instillation Normal saline instillation' |
Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Mean Change of the Total Frequency Per 3 Days
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy: Mean change of the total frequency per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value |
Baseline to 4 weeks after initial treatment
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Mean Change of the Urgency Episodes Per 3 Days
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy: Mean change of the Urgency episodes per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value |
Baseline to 4 weeks after initial treatment
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Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy: Mean change of the urgency urinary incontinence (UUI) per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value |
Baseline to 4 weeks after initial treatment
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Net Change of the Overactive Bladder Symptom Score (OABSS)
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy:(measured the net change of variables from baseline to 1 month) Overactive bladder symptom score (OABSS) The OABSS is a 4-item questionnaire developed to evaluate OAB symptoms. The maximal scores are 2, 3, 5 and 5 for daytime frequency, nighttime frequency, urgency and urgency in continence, respectively. The OABSS range = 0 to 15 ((asymptomatic to very symptomatic). Change = Week 4 minus Baseline value |
Baseline to 4 weeks after initial treatment
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Net Change of the Functional Bladder Capacity (FBC)
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value
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Baseline to 4 weeks after initial treatment
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Net Change of the Maximum Flow Rate (Qmax)
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value
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Baseline to 4 weeks after initial treatment
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Net Change of the Postvoid Residual Volume (PVR)
Prazo: Baseline and 1 month after initial treatment
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Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value
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Baseline and 1 month after initial treatment
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Net Change of the Urgency Severity Score (USS) Within 3 Days
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy:(measured the net change of variables from baseline and 1 month) Urgency severity score (USS) within 3 days.
The USS have 1-point scale ranging from 0 to 4. The USS grades urgency per toilet void as none, mild, moderate or severe.
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Baseline to 4 weeks after initial treatment
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Net Change of the Global Response Assessment (GRA)
Prazo: Baseline to 4 weeks after initial treatment
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Efficacy:(measured the net change of variables from baseline and 1 month) The Global response assessment (GRA) have seven point scale is centered at zero (no change): markedly worse; moderately worse; slightly worse; no change; slightly improved; moderately improved; and markedly improved.
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Baseline to 4 weeks after initial treatment
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Yao-Chi Chuang, M.D., Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de maio de 2010
Conclusão Primária (Real)
1 de dezembro de 2013
Conclusão do estudo (Real)
1 de dezembro de 2013
Datas de inscrição no estudo
Enviado pela primeira vez
20 de julho de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
20 de julho de 2010
Primeira postagem (Estimativa)
22 de julho de 2010
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
22 de setembro de 2014
Última atualização enviada que atendeu aos critérios de controle de qualidade
19 de setembro de 2014
Última verificação
1 de setembro de 2014
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Urológicas
- Doenças da Bexiga Urinária
- Sintomas do Trato Urinário Inferior
- Manifestações Urológicas
- Bexiga Urinária Hiperativa
- Efeitos Fisiológicos das Drogas
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Agentes do Sistema Nervoso Periférico
- Agentes colinérgicos
- Moduladores de transporte de membrana
- Inibidores da Liberação de Acetilcolina
- Agentes Neuromusculares
- Toxinas Botulínicas
- Toxinas Botulínicas, Tipo A
- toxina abobotulínica A
Outros números de identificação do estudo
- TCGHUROL001
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