Overactive BladderPhase 2NCT01167257
Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome
A Phase 2 study testing Liposome encapsulated botulinum toxin A and Normal saline instillation in people with Overactive Bladder, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Overactive Bladder
- What is being tested?
- Liposome encapsulated botulinum toxin A and Normal saline instillation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteTaiwan
- Study dates
- May 2010to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Overactive Bladder
- Being tested
- Liposome encapsulated botulinum toxin A, Normal saline instillation
- Keywords
- Overactive bladder, Detrusor overactivity, Liposome, Botulinum toxin A
- Medical subject headings
- Urinary Bladder, Overactive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposome encapsulated botulinum toxin ADrug
Also called Lipotoxin
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
Normal saline instillationDrug
Also called N/S
Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | 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' Receives: Drug: Liposome encapsulated botulinum toxin A |
| Control arm | Placebo comparator | Normal saline 50 mL in single intravesical instillation
Normal saline instillation' Receives: Drug: Normal saline instillation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change of the Total Frequency Per 3 Days
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
Measured: Baseline to 4 weeks after initial treatment
Secondary outcomes (8)
Mean Change of the Urgency Episodes Per 3 Days
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
Measured: Baseline to 4 weeks after initial treatment
Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days
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
Measured: Baseline to 4 weeks after initial treatment
Net Change of the Overactive Bladder Symptom Score (OABSS)
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
Measured: Baseline to 4 weeks after initial treatment
Net Change of the Functional Bladder Capacity (FBC)
Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value
Measured: Baseline to 4 weeks after initial treatment
Net Change of the Maximum Flow Rate (Qmax)
Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value
Measured: Baseline to 4 weeks after initial treatment
Net Change of the Postvoid Residual Volume (PVR)
Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value
Measured: Baseline and 1 month after initial treatment
Net Change of the Urgency Severity Score (USS) Within 3 Days
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.
Measured: Baseline to 4 weeks after initial treatment
Net Change of the Global Response Assessment (GRA)
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.
Measured: Baseline to 4 weeks after initial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2010 (estimated)
- Study startMay 2010
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Overactive BladderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Buddhist Tzu Chi General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital
- Investigators
- Hann-Chorng Kuo, M.D., Principal investigator, Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi UniversityYao-Chi Chuang, M.D., Principal investigator, Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01167257
- Sponsor's protocol ID
- TCGHUROL001
- Status last verified
- Sep 2014
- First submitted
- 20 Jul 2010
- Last updated
- 22 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01167257
- Acronym / sponsor ID
- TCGHUROL001
- Conditions
- Overactive Bladder
- Keywords
- Overactive bladder, Detrusor overactivity, Liposome, Botulinum toxin A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Buddhist Tzu Chi General HospitalUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 22 Jul 2010 (estimated)
- Results
- Posted 22 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Liposome encapsulated botulinum toxin ALiposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL in Liposome 80 mg/40 mL) in single intravesical instillation Liposome encapsulated botulinum toxin A' |
| Control arm | Placebo comparator | Drug: Normal saline instillationNormal saline 50 mL in single intravesical instillation Normal saline instillation' |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposome encapsulated botulinum toxin AAlso: LipotoxinLiposome 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 | Drug | Experimental arm |
| Normal saline instillationAlso: N/SNormal saline (BoNT-A/NS) 50 mL in single intravesical instillation | Drug | Control arm |
Primary outcome
Mean Change of the Total Frequency Per 3 Days
Time frame: 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
8 secondary outcomes
Mean Change of the Urgency Episodes Per 3 Days
Time frame: Baseline to 4 weeks after initial treatment
Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days
Time frame: Baseline to 4 weeks after initial treatment
Net Change of the Overactive Bladder Symptom Score (OABSS)
Time frame: Baseline to 4 weeks after initial treatment
Net Change of the Functional Bladder Capacity (FBC)
Time frame: Baseline to 4 weeks after initial treatment
Net Change of the Maximum Flow Rate (Qmax)
Time frame: Baseline to 4 weeks after initial treatment
Net Change of the Postvoid Residual Volume (PVR)
Time frame: Baseline and 1 month after initial treatment
Net Change of the Urgency Severity Score (USS) Within 3 Days
Time frame: Baseline to 4 weeks after initial treatment
Net Change of the Global Response Assessment (GRA)
Time frame: Baseline to 4 weeks after initial treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hann-Chorng Kuo, M.D. principal investigator
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University
Yao-Chi Chuang, M.D. principal investigator
Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liposome encapsulated botulinum toxin A and Normal saline instillation in people with Overactive Bladder, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change of the Total Frequency Per 3 Days (time frame: Baseline to 4 weeks after initial treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2014.