<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02247557</url>
  </required_header>
  <id_info>
    <org_study_id>TCGHUROL011</org_study_id>
    <nct_id>NCT02247557</nct_id>
  </id_info>
  <brief_title>Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis</brief_title>
  <official_title>Intravesical Instillation of Liposome Encapsulated Botulinum Toxin A (Lipotoxin) in Treatment of Interstitial Cystitis - a Randomized, Double-blind, Placebo-controlled, Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Buddhist Tzu Chi General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Buddhist Tzu Chi General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy and safety of intravesical instillation of Lipotoxin for the&#xD;
      treatment of IC/BPS&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liposome has been proven able to carry botulinum toxin protein across the cell membrane and&#xD;
      effect on urothelial receptors in human overactive bladder. However, the therapeutic duration&#xD;
      is limited to 1 month. Intravesical BOTOX injection in patients with interstitial cystitis&#xD;
      (IC) can effectively decrease pain, improve bladder capacity and decrease frequency. However,&#xD;
      the need of cystoscopic injection limits its wide application.&#xD;
&#xD;
      A total of 100 eligible women with non-ulcer IC will be enrolled to receive intravesical&#xD;
      instillation of Lipotoxin containing 80mg liposomes and 200U BOTOX (treatment group), 200U&#xD;
      BOTOX in normal saline (N/S) (active control group) or normal saline (placebo control group)&#xD;
      single treatment. At least 90 evaluable patients will be included for the final analysis.&#xD;
&#xD;
      All patients should have IC symptoms for at least 6 months, and proven to have grade 2&#xD;
      diffused glomerulations after cystoscopic hydrodistention (HD) within recent 1 year without&#xD;
      Hunner's lesion. Patients should not have UTI in recent 12 months, no urinary tract stone.&#xD;
      Patients should have been proven free of detrusor overactivity or bladder outlet obstruction.&#xD;
      Patients should not receive intravesical hyaluronic acid treatment in recent 6 months, or&#xD;
      intravesical Botox injection in recent 12 months. Intravesical instillation of Lipotoxin at&#xD;
      OPD and the patient should hold the solution for 2 hours to allow bladder distention.&#xD;
      Retreatment with Lipotoxin at 3 months if patient reports ineffective.&#xD;
&#xD;
      Primary end-point is the change of the O'Leary-Sant symptom score (including ICSI and ICPI)&#xD;
      from baseline to 1 month after treatment. Secondary endpoints include VAS, daily frequency,&#xD;
      nocturia and FBC as record in 3-day voiding diary, Qmax, voided volume, PVR and global&#xD;
      response assessment (GRA). Four visits are required at baseline screening (before first&#xD;
      treatment), treatment (V1), 2 weeks (V2), 4 weeks (V3, primary end-point) and 12 weeks (V4).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>All participants, investigators and care providers do not know which regimen is given to patients of the three arms.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change of the O'Leary-Sant symptom score</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Net changes of the Visual Analog Scale (VAS)</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the Visual Analog Scale from baseline to 1 month after the treatment day&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net changes of the functional bladder capacity (FBC)</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the functional bladder capacity from baseline to 1 month after the treatment day&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the voiding frequency at daytime from baseline to 1 month after the treatment day&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net changes of the voiding frequency at night time as recorded in 3-day voiding diary</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the voiding night time from baseline to 1 month after the treatment day&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the Global response assessment (GRA)</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>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.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the maximum flow rate</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the maximum flow rate from baseline to 1 month after the treatment day.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the voided volume</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the voided volume from baseline to 1 month after the treatment day.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the PVR</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Net changes of the PVR from baseline to 1 month after the treatment day.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the urinary nerve growth factor</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Changes of urinary nerve growth factor from baseline to 1 month after treatment day.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net Change of the cytokines level</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Changes of cytokines level from baseline to 1 month after treatment day.&#xD;
Safety&#xD;
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Interstitial Cystitis</condition>
  <arm_group>
    <arm_group_label>Group A: Liposome encapsulated BoNT-A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: BoNT-A 200 U in Normal saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C: Normal saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline (N/S) 50ml in single intravesical instillation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposome encapsulated BoNT-A</intervention_name>
    <description>Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation</description>
    <arm_group_label>Group A: Liposome encapsulated BoNT-A</arm_group_label>
    <other_name>Liposome</other_name>
    <other_name>onabotulinumtoxinA 200U</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BOTOX 200U in normal saline</intervention_name>
    <description>BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation</description>
    <arm_group_label>Group B: BoNT-A 200 U in Normal saline</arm_group_label>
    <other_name>onabotulinumtoxinA 200U</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>Normal saline (N/S) 50ml in single intravesical instillation</description>
    <arm_group_label>Group C: Normal saline</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults with age of 20 years old or above&#xD;
&#xD;
          2. Patients with symptoms of frequency, urgency, nocturia, and/or bladder pain.&#xD;
&#xD;
          3. Proven to have glomerulations (at least grade 2) by cystoscopic hydrodistention under&#xD;
             anesthesia in recent 1 year&#xD;
&#xD;
          4. Free of active urinary tract infection&#xD;
&#xD;
          5. Free of bladder outlet obstruction on enrollment&#xD;
&#xD;
          6. Free of overt neurogenic bladder dysfunction and limitation of ambulation&#xD;
&#xD;
          7. Patient or his/her legally acceptable representative has signed the written informed&#xD;
             consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hunner's lesion proven by cystoscopy&#xD;
&#xD;
          2. Patients with severe cardiopulmonary disease and such as congestive heart failure,&#xD;
             arrhythmia, poorly controlled hypertension, not able to receive regular follow-up&#xD;
&#xD;
          3. Patients with bladder outlet obstruction on enrollment&#xD;
&#xD;
          4. Patients with postvoid residual &gt;250ml&#xD;
&#xD;
          5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection&#xD;
&#xD;
          6. Patients have laboratory abnormalities at screening including: ALT&gt; 3 x upper limit of&#xD;
             normal range, AST&gt; 3 x upper limit of normal range; Patients have abnormal serum&#xD;
             creatinine level &gt; 2 x upper limit of normal range&#xD;
&#xD;
          7. Patients with any contraindication to be urethral catheterization during treatment&#xD;
&#xD;
          8. Female patients who is pregnant, lactating, or with child-bearing potential without&#xD;
             contraception.&#xD;
&#xD;
          9. Myasthenia gravis, Eaton Lambert syndrome.&#xD;
&#xD;
         10. Patients with any other serious disease considered by the investigator not in the&#xD;
             condition to enter the trial&#xD;
&#xD;
         11. Patient had received intravesical treatment for IC within recent 1 month&#xD;
&#xD;
         12. Patients participated investigational drug trial within 1 month before entering this&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hann-Chorng Kuo, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Urology, Buddihisst Tzu Chi General Hospital and Tzu Chi University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Buddhist Tzu Chi General Hospital</name>
      <address>
        <city>Hualien</city>
        <zip>970</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>March 7, 2017</last_update_submitted>
  <last_update_submitted_qc>March 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Buddhist Tzu Chi General Hospital</investigator_affiliation>
    <investigator_full_name>Hann-Chorng Kuo</investigator_full_name>
    <investigator_title>Director of Urology</investigator_title>
  </responsible_party>
  <keyword>IC/PBS</keyword>
  <keyword>VAS</keyword>
  <keyword>Botulinum Toxin A</keyword>
  <keyword>Lipotoxin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystitis</mesh_term>
    <mesh_term>Cystitis, Interstitial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD cannot be released unless researchers obtain the approval from the Ethics Committee of the Buddhist Tzu Chi General Hospital, Hualien, Taiwan</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02247557
org study id: TCGHUROL011
nct id: NCT02247557
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To evaluate the efficacy and safety of intravesical instillation of Lipotoxin for the
      treatment of IC/BPS
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).
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.
primary purpose: Treatment
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.
measure: Change of the O'Leary-Sant symptom score
time frame: Baseline and 1 month
description: Change of the O'Leary-Sant symptom score from baseline to 1 month after the treatment day
measure: Net changes of the Visual Analog Scale (VAS)
time frame: Baseline and 1 month
description: 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).
measure: Net changes of the functional bladder capacity (FBC)
time frame: Baseline and 1 month
description: 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).
measure: Net changes of the voiding frequency at daytime as recorded in 3-day voiding diary
time frame: Baseline and 1 month
description: 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).
measure: Net changes of the voiding frequency at night time as recorded in 3-day voiding diary
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the Global response assessment (GRA)
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the maximum flow rate
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the voided volume
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the PVR
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the urinary nerve growth factor
time frame: Baseline and 1 month
description: 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).
measure: Net Change of the cytokines level
time frame: Baseline and 1 month
description: Changes of cytokines level from baseline to 1 month after treatment day.
Safety
(1) Local adverse event incidences (hematuria, miction pain, UTI, urinary retention).
arm group label: Group A: Liposome encapsulated BoNT-A
arm group type: Experimental
description: Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
arm group label: Group B: BoNT-A 200 U in Normal saline
arm group type: Experimental
description: BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
arm group label: Group C: Normal saline
arm group type: Placebo Comparator
description: Normal saline (N/S) 50ml in single intravesical instillation
intervention type: Drug
intervention name: Liposome encapsulated BoNT-A
description: Liposome encapsulated BoNT-A ( mixed BOTOX 200U/10ml in Liposome 80mg/40ml) in single intravesical instillation
arm group label: Group A: Liposome encapsulated BoNT-A
other name: Liposome
other name: onabotulinumtoxinA 200U
intervention type: Drug
intervention name: BOTOX 200U in normal saline
description: BOTOX 200U in normal saline (BoNT-A/NS) 50ml in single intravesical instillation
arm group label: Group B: BoNT-A 200 U in Normal saline
other name: onabotulinumtoxinA 200U
intervention type: Drug
intervention name: Normal saline
description: Normal saline (N/S) 50ml in single intravesical instillation
arm group label: Group C: Normal saline
other name: Saline
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hann-Chorng Kuo, M.D.
role: Principal Investigator
affiliation: Department of Urology, Buddihisst Tzu Chi General Hospital and Tzu Chi University
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Buddhist Tzu Chi General Hospital
investigator full name: Hann-Chorng Kuo
investigator title: Director of Urology
mesh term: Cystitis
mesh term: Cystitis, Interstitial
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: No
ipd description: IPD cannot be released unless researchers obtain the approval from the Ethics Committee of the Buddhist Tzu Chi General Hospital, Hualien, Taiwan