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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Buddhist Tzu Chi General Hospital
Sponsor:
Information provided by (Responsible Party):
Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital
ClinicalTrials.gov Identifier:
NCT01167257
First received: July 20, 2010
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Overactive Bladder
Drug: Liposome encapsulated botulinum toxin A
Drug: Normal saline instillation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Buddhist Tzu Chi General Hospital:

Primary Outcome Measures:
  • Total frequency within 3 days from baseline to 1 month after the treatment day [ Time Frame: one month after initial treatment ] [ Designated as safety issue: Yes ]

    Efficacy:

    Net change of the total frequency within 3 days from baseline to 1 month after the treatment day based on the record of the 3-day voiding diary

    Safety:

    1. Local adverse event incidences (hematuria, miction pain, urinary tract infection, urinary retention)
    2. Systemic adverse events.


Secondary Outcome Measures:
  • Voiding and urodynamic parameters [ Time Frame: One month after the initial treatment day ] [ Designated as safety issue: Yes ]

    Efficacy:(measured the net change of variables from baseline to 1 month)

    1. Urgency episodes/3 days
    2. Urgency urinary incontinence (UUI)/3 days
    3. Overactive bladder symptom score (OABSS)
    4. Urgency severity score (USS)
    5. Functional bladder capacity (FBC)
    6. Maximum flow rate (Qmax)
    7. Postvoid residual volume (PVR)
    8. Global response assessment (GRA) of satisfaction by the patient
    9. Urodynamic parameters from baseline to 3 months

    Safety:

    1. Local adverse event incidences (hematuria, miction pain, urinary tract infection, urinary retention)
    2. Systemic adverse events.


Estimated Enrollment: 80
Study Start Date: May 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental arm
Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10ml in Liposome 80mg/40ml) in single intravesical instillation
Drug: Liposome encapsulated botulinum toxin A
Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10ml water in Liposome 80mg/40ml water) in single intravesical instillation, one time treatment at the treatment day
Other Name: Lipotoxin
Placebo Comparator: Control arm
Normal saline 50ml in single intravesical instillation
Drug: Normal saline instillation
Normal saline (BoNT-A/NS) 50ml in single intravesical instillation
Other Name: N/S

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 > 150ml
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01167257

Contacts
Contact: Hann-Chorng Kuo, M.D. 886-3-8561825 ext 2113 hck@tzuchi.com.tw
Contact: Dong-Ling Tang, Miss 886-3-8561825 ext 2117 hck@tzuchi.com.tw

Locations
Taiwan
Buddhist Tzu Chi General Hospital Not yet recruiting
Hualien, Taiwan, 970
Contact: Hann-Chorng Kuo, M.D.    886-3-8561825 ext 2117    hck@tzuchi.com.tw   
Contact: Huey-Men Chang, M.S.    886-3-8561825 ext 2113    tcmj@tzuchi.com.tw   
Principal Investigator: Hann-Chorng Kuo, M.D.         
Buddhist Tzu Chi General Hospital Recruiting
Hualien, Taiwan, 970
Contact: Hann-Chorng Kuo, M.D.    886-3-8561825 ext 2117    hck@tzuchi.com.tw   
Contact: Dong-Ling Tang, Miss    886-3-8561825 ext 2117    hck@tzuchi.com.tw   
Principal Investigator: Hann-Chorng Kuo, M.D.         
Sponsors and Collaborators
Buddhist Tzu Chi General Hospital
Investigators
Principal Investigator: Hann-Chorng Kuo, M.D. Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University
Principal Investigator: Yao-Chi Chuang, M.D. Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
  More Information

No publications provided

Responsible Party: Hann-Chorng Kuo, Department of Urology, Buddhist Tzu Chi General Hospital
ClinicalTrials.gov Identifier: NCT01167257     History of Changes
Other Study ID Numbers: TCGHUROL001
Study First Received: July 20, 2010
Last Updated: February 20, 2013
Health Authority: Taiwan: Center for Drug Evaluation
Taiwan: Department of Health
Taiwan: Research Ethics Committee

Keywords provided by Buddhist Tzu Chi General Hospital:
Overactive bladder
Detrusor overactivity
Liposome
Botulinum toxin A

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014