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Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital
ClinicalTrials.gov Identifier:
NCT02247557
First received: September 15, 2014
Last updated: March 7, 2017
Last verified: March 2017
  Purpose
To evaluate the efficacy and safety of intravesical instillation of Lipotoxin for the treatment of IC/BPS

Condition Intervention Phase
Interstitial Cystitis Drug: Liposome encapsulated BoNT-A Drug: BOTOX 200U in normal saline Drug: Normal saline Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a double-blind, randomized, placebo-controlled physician initiated study enrolled patients with refractory IC/BPS. Patients were assigned to intravesical instillation of lipotoxin (onabotulinumtoxinA 200 U with 80mg sphingomyelin), onabotulinumtoxinA 200 U in normal saline, or normal saline.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
All participants, investigators and care providers do not know which regimen is given to patients of the three arms.
Primary Purpose: Treatment
Official Title: Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis — a Randomized, Double-blind, Placebo-controlled, Prospective Study

Resource links provided by NLM:


Further study details as provided by Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital:

Primary Outcome Measures:
  • Change of the O'Leary-Sant symptom score [ Time Frame: Baseline and 1 month ]
    Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day


Secondary Outcome Measures:
  • Net changes of the Visual Analog Scale (VAS) [ Time Frame: Baseline and 1 month ]

    Net changes of the Visual Analog Scale from baseline to 1 month after the treatment day

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net changes of the functional bladder capacity (FBC) [ Time Frame: Baseline and 1 month ]

    Net changes of the functional bladder capacity from baseline to 1 month after the treatment day

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary [ Time Frame: Baseline and 1 month ]

    Net changes of the voiding frequency at daytime from baseline to 1 month after the treatment day

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net changes of the voiding frequency at night time as recorded in 3-day voiding diary [ Time Frame: Baseline and 1 month ]

    Net changes of the voiding night time from baseline to 1 month after the treatment day

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the Global response assessment (GRA) [ Time Frame: Baseline and 1 month ]

    Global response assessment (GRA) of therapeutic result by the patient (categorized from -3 to +3, indicating markedly worse to markedly improved) at 3 months after the treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the maximum flow rate [ Time Frame: Baseline and 1 month ]

    Net changes of the maximum flow rate from baseline to 1 month after the treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the voided volume [ Time Frame: Baseline and 1 month ]

    Net changes of the voided volume from baseline to 1 month after the treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the PVR [ Time Frame: Baseline and 1 month ]

    Net changes of the PVR from baseline to 1 month after the treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the urinary nerve growth factor [ Time Frame: Baseline and 1 month ]

    Changes of urinary nerve growth factor from baseline to 1 month after treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).


  • Net Change of the cytokines level [ Time Frame: Baseline and 1 month ]

    Changes of cytokines level from baseline to 1 month after treatment day.

    Safety

    (1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).



Enrollment: 90
Actual Study Start Date: September 2014
Study Completion Date: February 2017
Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: Liposome encapsulated BoNT-A
Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
Drug: Liposome encapsulated BoNT-A
Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
Other Names:
  • Liposome
  • onabotulinumtoxinA 200U
Experimental: Group B: BoNT-A 200 U in Normal saline
BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
Drug: BOTOX 200U in normal saline
BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
Other Name: onabotulinumtoxinA 200U
Placebo Comparator: Group C: Normal saline
Normal saline (N/S) 50ml in single intravesical instillation
Drug: Normal saline
Normal saline (N/S) 50ml in single intravesical instillation
Other Name: Saline

Detailed Description:

Liposome has been proven able to carry botulinum toxin protein across the cell membrane and effect on urothelial receptors in human overactive bladder. However, the therapeutic duration is limited to 1 month. Intravesical BOTOX injection in patients with interstitial cystitis (IC) can effectively decrease pain, improve bladder capacity and decrease frequency. However, the need of cystoscopic injection limits its wide application.

A total of 100 eligible women with non-ulcer IC will be enrolled to receive intravesical instillation of Lipotoxin containing 80mg liposomes and 200U BOTOX (treatment group), 200U BOTOX in normal saline (N/S) (active control group) or normal saline (placebo control group) single treatment. At least 90 evaluable patients will be included for the final analysis.

All patients should have IC symptoms for at least 6 months, and proven to have grade 2 diffused glomerulations after cystoscopic hydrodistention (HD) within recent 1 year without Hunner's lesion. Patients should not have UTI in recent 12 months, no urinary tract stone. Patients should have been proven free of detrusor overactivity or bladder outlet obstruction. Patients should not receive intravesical hyaluronic acid treatment in recent 6 months, or intravesical Botox injection in recent 12 months. Intravesical instillation of Lipotoxin at OPD and the patient should hold the solution for 2 hours to allow bladder distention. Retreatment with Lipotoxin at 3 months if patient reports ineffective.

Primary end-point is the change of the O'Leary-Sant symptom score (including ICSI and ICPI) from baseline to 1 month after treatment. Secondary endpoints include VAS, daily frequency, nocturia and FBC as record in 3-day voiding diary, Qmax, voided volume, PVR and global response assessment (GRA). Four visits are required at baseline screening (before first treatment), treatment (V1), 2 weeks (V2), 4 weeks (V3, primary end-point) and 12 weeks (V4).

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults with age of 20 years old or above
  2. Patients with symptoms of frequency, urgency, nocturia, and/or bladder pain.
  3. Proven to have glomerulations (at least grade 2) by cystoscopic hydrodistention under anesthesia in recent 1 year
  4. Free of active urinary tract infection
  5. Free of bladder outlet obstruction on enrollment
  6. Free of overt neurogenic bladder dysfunction and limitation of ambulation
  7. Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

  1. Hunner's lesion proven by cystoscopy
  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 >250ml
  5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
  6. Patients have laboratory abnormalities at screening including: ALT> 3 x upper limit of normal range, 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 in the condition to enter the trial
  11. Patient had received intravesical treatment for IC within recent 1 month
  12. 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: NCT02247557

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, Buddihisst Tzu Chi General Hospital and Tzu Chi University
  More Information

Responsible Party: Hann-Chorng Kuo, Director of Urology, Buddhist Tzu Chi General Hospital
ClinicalTrials.gov Identifier: NCT02247557     History of Changes
Other Study ID Numbers: TCGHUROL011
Study First Received: September 15, 2014
Last Updated: March 7, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD cannot be released unless researchers obtain the approval from the Ethics Committee of the Buddhist Tzu Chi General Hospital, Hualien, Taiwan

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Hann-Chorng Kuo, Buddhist Tzu Chi General Hospital:
IC/PBS
VAS
Botulinum Toxin A
Lipotoxin

Additional relevant MeSH terms:
Cystitis
Cystitis, Interstitial
Urinary Bladder Diseases
Urologic Diseases
Botulinum Toxins
onabotulinumtoxinA
Botulinum Toxins, Type A
abobotulinumtoxinA
incobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 23, 2017