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

This study has been completed.
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: September 19, 2014
Last verified: September 2014
  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:
  • Mean Change of the Total Frequency Per 3 Days [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Mean Change of the Urgency Episodes Per 3 Days [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]

    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


  • Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]

    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


  • Net Change of the Overactive Bladder Symptom Score (OABSS) [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]

    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


  • Net Change of the Functional Bladder Capacity (FBC) [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]
    Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value

  • Net Change of the Maximum Flow Rate (Qmax) [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]
    Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value

  • Net Change of the Postvoid Residual Volume (PVR) [ Time Frame: Baseline and 1 month after initial treatment ] [ Designated as safety issue: No ]
    Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value

  • Net Change of the Urgency Severity Score (USS) Within 3 Days [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]
    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.

  • Net Change of the Global Response Assessment (GRA) [ Time Frame: Baseline to 4 weeks after initial treatment ] [ Designated as safety issue: No ]
    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.


Enrollment: 62
Study Start Date: May 2010
Study Completion Date: December 2013
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/10 mL in Liposome 80 mg/40 mL) in single intravesical instillation

Liposome encapsulated botulinum toxin A'

Drug: 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
Other Name: Lipotoxin
Placebo Comparator: Control arm

Normal saline 50 mL in single intravesical instillation

Normal saline instillation'

Drug: Normal saline instillation
Normal saline (BoNT-A/NS) 50 mL 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 >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
  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

Locations
Taiwan
Buddhist Tzu Chi General Hospital
Hualien, Taiwan, 970
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
Results First Received: September 10, 2014
Last Updated: September 19, 2014
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
Lower Urinary Tract Symptoms
Signs and Symptoms
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014