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

NCT ID: NCT01167257

Last Updated: 2014-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2013-12-31

Brief 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. 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.

Conditions

Overactive Bladder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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'

Group Type: EXPERIMENTAL

Liposome encapsulated botulinum toxin A

Intervention Type: DRUG

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

Control arm

Normal saline 50 mL in single intravesical instillation

Normal saline instillation'

Group Type: PLACEBO_COMPARATOR

Normal saline instillation

Intervention Type: DRUG

Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation

Interventions

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

Intervention Type: DRUG

Normal saline instillation

Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation

Intervention Type: DRUG

Other Intervention Names

Lipotoxin; N/S

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Buddhist Tzu Chi General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hann-Chorng Kuo

Department of Urology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hann-Chorng Kuo, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

Yao-Chi Chuang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Locations

Buddhist Tzu Chi General Hospital

Hualien City, , Taiwan

Countries

Taiwan

Other Identifiers

TCGHUROL001

Identifier Type: -

Identifier Source: org_study_id