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Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome

19. september 2014 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

62

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Taiwan
      • Hualien, Taiwan, 970
        • Buddhist Tzu Chi General Hospital

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 og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Adults with age of 20 years old or above
  2. 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)
  3. Free of active urinary tract infection
  4. Free of bladder outlet obstruction on enrollment
  5. Free of overt neurogenic bladder dysfunction
  6. Having been treated with antimuscarinic agents for at least 4 weeks without effect or with intolerable adverse effects
  7. Patient has not been treated with bladder surgery for OAB, such as enterocystoplasty, that might affect the therapeutic effect of test drug
  8. Patient can record voiding diary for the urinary frequency and urgency
  9. Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

  1. Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms
  2. Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
  3. Patients with bladder outlet obstruction on enrollment
  4. Patients with postvoid residual >150 mL
  5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection

  6. 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

  7. Patients with any contraindication to be urethral catheterization during treatment
  8. Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
  9. Myasthenia gravis, Eaton Lambert syndrome.
  10. Patients with any other serious disease considered by the investigator not suitable for general anesthesia or in the condition to enter the trial
  11. Patients participated investigational drug trial within 1 month before entering this study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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'
Medicin: 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
Andre navne:
  • Lipotoxin
Placebo komparator: Control arm

Normal saline 50 mL in single intravesical instillation

Normal saline instillation'
Medicin: Normal saline instillation
Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation
Andre navne:
  • N/S

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Mean Change of the Total Frequency Per 3 Days
Tidsramme: Baseline to 4 weeks after initial treatment

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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Mean Change of the Urgency Episodes Per 3 Days
Tidsramme: Baseline to 4 weeks after initial treatment

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
Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days
Tidsramme: Baseline to 4 weeks after initial treatment

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
Net Change of the Overactive Bladder Symptom Score (OABSS)
Tidsramme: Baseline to 4 weeks after initial treatment

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
Net Change of the Functional Bladder Capacity (FBC)
Tidsramme: Baseline to 4 weeks after initial treatment
Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value
Baseline to 4 weeks after initial treatment
Net Change of the Maximum Flow Rate (Qmax)
Tidsramme: Baseline to 4 weeks after initial treatment
Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value
Baseline to 4 weeks after initial treatment
Net Change of the Postvoid Residual Volume (PVR)
Tidsramme: Baseline and 1 month after initial treatment
Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value
Baseline and 1 month after initial treatment
Net Change of the Urgency Severity Score (USS) Within 3 Days
Tidsramme: Baseline to 4 weeks after initial treatment
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.
Baseline to 4 weeks after initial treatment
Net Change of the Global Response Assessment (GRA)
Tidsramme: Baseline to 4 weeks after initial treatment
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.
Baseline to 4 weeks after initial treatment

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Buddhist Tzu Chi General Hospital

Efterforskere

  • Ledende efterforsker: Yao-Chi Chuang, M.D., Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

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. maj 2010

Primær færdiggørelse (Faktiske)

1. december 2013

Studieafslutning (Faktiske)

1. december 2013

Datoer for studieregistrering

Først indsendt

20. juli 2010

Først indsendt, der opfyldte QC-kriterier

20. juli 2010

Først opslået (Skøn)

22. juli 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

22. september 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

19. september 2014

Sidst verificeret

1. september 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • TCGHUROL001

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