<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/NCT04401176</url>
  </required_header>
  <id_info>
    <org_study_id>EKW_01-2020</org_study_id>
    <nct_id>NCT04401176</nct_id>
  </id_info>
  <brief_title>Bladder Instillations Versus Onabotulinumtoxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome</brief_title>
  <official_title>A Randomized Trial of Bladder Instillations Versus Onabotulinumtoxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Walter Reed National Military Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Walter Reed National Military Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recognition of interstitial cystitis (IC)/bladder pain syndrome (BPS) is increasing. There is&#xD;
      a dire need to develop effective treatment options for these patients as it manifests as more&#xD;
      than a physical disease, affecting general and psychological health as well. Existing trials&#xD;
      comparing varying bladder instillation formulations have not identified an optimal bladder&#xD;
      instillation therapy, however existing studies support combined heparin and alkalinized&#xD;
      lidocaine bladder instillation as an affordable and effective treatment for IC/BPS.&#xD;
      Additionally, intradetrusor onabotulinumtoxinA injection has been well established for the&#xD;
      treatment of overactive bladder (OAB), a constellation of symptoms similar to that of IC/BPS.&#xD;
      OnabotulinumtoxinA has now come into the forefront for treatment of OAB due to its efficacy,&#xD;
      safety profile, and absence of cognitive effects related to the previous mainstay&#xD;
      anticholinergic treatment. While both bladder instillation and onabotulinumtoxinA therapy&#xD;
      have been shown to be effective for treatment of IC/BPS, a direct comparison of these&#xD;
      treatments has not been performed. We therefore designed a randomized controlled trial to&#xD;
      compare the efficacy of heparin with alkalized local anesthetic bladder instillation versus&#xD;
      intradetrusor onabotulinumtoxinA injection in treating IC/BPS symptoms.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 15, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 8-10 weeks</time_frame>
    <description>Consists of O'Leary-Sant Symptom and Problem Index, total score 0-36.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 6-9 months</time_frame>
    <description>Consists of O'Leary-Sant Symptom and Problem Index. Total score 0-36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pain scores using the Defense and Veterans Pain Rating Scale (visual analog scale) between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 8-10 weeks, 6-9 months</time_frame>
    <description>Scale of 0-10 (0= no pain, 10 = worst pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Female Sexual Function Index (FSFI) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 8-10 weeks</time_frame>
    <description>FSFI evaluates 5 domains of female sexual function including desire, arousal, lubrication, orgasm, satisfaction, and pain. Total score 2-36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Female Sexual Distress Scale-Revised (FSDS-R) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 8-10 weeks</time_frame>
    <description>FSDS-R evaluates distress associated with inadequate/impaired sexual function. Total score 0-52.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 12-item Short Form Survey (SF-12) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 8-10 weeks</time_frame>
    <description>SF-12 is a general health questionnaire that evaluates quality of life measures, divided into mental and physical component scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bladder capacity between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>Baseline, 4-6 weeks, 8-10 weeks</time_frame>
    <description>Bladder capacity via 1-day bladder diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse outcomes between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>8-10 weeks</time_frame>
    <description>Adverse outcomes to be defined specific to medication administered (urinary tract infection in both bladder instillation and onabotulinumtoxinA injection groups, urinary retention requiring catheterization, systemic effects related to onabotulinumtoxinA group only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient perceptions of treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>6-9 months</time_frame>
    <description>&quot;How convenient or inconvenient was it to follow the treatment schedule as instructed?&quot; (Scale 1-5 extremely inconvenient - extremely convenient) &quot;How satisfied or dissatisfied are you in the ability of the treatment to treat your condition?&quot; (Scale 1-5 extremely dissatisfied - extremely satisfied) &quot;Taking all things into account, how satisfied or dissatisfied are you with this treatment?&quot; (Scale 1-5 extremely dissatisfied - extremely satisfied) &quot;How willing would you be to undergo this treatment again?&quot; (Scale 1-5 extremely unwilling - extremely willing).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of re-treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups</measure>
    <time_frame>6-9 months</time_frame>
    <description>Re-treatment defined as additional course or crossover treatment outside of assigned treatment group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Interstitial Cystitis</condition>
  <condition>Bladder Pain Syndrome</condition>
  <arm_group>
    <arm_group_label>Heparin &amp; Alkalinized Lidocaine Bladder Instillation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Six weekly bladder instillations, each instillation consisting of 40,000 IU Heparin, 200mg lidocaine, 2ml 8.4% sodium bicarbonate, sterile water for a total volume 50 milliliters (mL).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intradetrusor Onabotulinumtoxin A Injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>100 units onabotulinumtoxinA reconstituted in 10mL of injectable saline, injected in 20 sites with 0.5mL per injection along the posterior wall of the bladder above the trigone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Heparin &amp; Alkalinized Lidocaine Bladder Instillation</intervention_name>
    <description>Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void</description>
    <arm_group_label>Heparin &amp; Alkalinized Lidocaine Bladder Instillation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Onabotulinum Toxin A</intervention_name>
    <description>Intradetrusor onabotulinumtoxinA injection (0.5mL x 20 sites)</description>
    <arm_group_label>Intradetrusor Onabotulinumtoxin A Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females ≥ 18 years of age&#xD;
&#xD;
          -  O'Leary-Sant questionnaire score ≥ 6&#xD;
&#xD;
          -  Ability to follow study instructions and complete all required follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications and/or allergies to medications used&#xD;
&#xD;
          -  Known alternative diagnosis explaining bladder pain symptoms&#xD;
&#xD;
          -  Bladder instillation within the past 3 months&#xD;
&#xD;
          -  Intradetrusor onabotulinumtoxinA injection within the past 6 months&#xD;
&#xD;
          -  Use of ≥ 400 units of onabotulinumtoxinA in the last 3 months&#xD;
&#xD;
          -  Inability or unwillingness to self-catheterize&#xD;
&#xD;
          -  Post-void residual &gt; 200mL&#xD;
&#xD;
          -  Concurrent procedural treatment (including hydrodistension, sacral neuromodulation)&#xD;
&#xD;
          -  Current use of vaginal pessary/devices&#xD;
&#xD;
          -  Untreated symptomatic prolapse &gt; pelvic organ prolapse quantification system (POP-Q)&#xD;
             stage 2&#xD;
&#xD;
          -  Females who are pregnant or planning a pregnancy during the study or who think that&#xD;
             they may be pregnant at the start of the study and who are unwilling or unable to use&#xD;
             a reliable form of contraception during the study&#xD;
&#xD;
          -  Inability to speak/read English&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Walter Reed National Military Medical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.auanet.org/guidelines/interstitial-cystitis-(ic/bps)-guideline</url>
    <description>American Urological Association Interstitial Cystitis Guidelines</description>
  </link>
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    <PMID>14979881</PMID>
  </reference>
  <reference>
    <citation>Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007 Sep;70(3):463-8. doi: 10.1016/j.urology.2007.04.038.</citation>
    <PMID>17905097</PMID>
  </reference>
  <reference>
    <citation>Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology. 2004 Nov;64(5):871-5; discussion 875. doi: 10.1016/j.urology.2004.06.073.</citation>
    <PMID>15533466</PMID>
  </reference>
  <reference>
    <citation>Giannantoni A, Costantini E, Di Stasi SM, Tascini MC, Bini V, Porena M. Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol. 2006 Apr;49(4):704-9. doi: 10.1016/j.eururo.2005.12.002. Epub 2006 Jan 4.</citation>
    <PMID>16417964</PMID>
  </reference>
  <reference>
    <citation>Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006 Apr;49(4):644-50. doi: 10.1016/j.eururo.2005.12.010. Epub 2006 Jan 4.</citation>
    <PMID>16426734</PMID>
  </reference>
  <reference>
    <citation>Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019 Aug 1;179(8):1084-1093. doi: 10.1001/jamainternmed.2019.0677.</citation>
    <PMID>31233095</PMID>
  </reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>June 17, 2022</last_update_submitted>
  <last_update_submitted_qc>June 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystitis</mesh_term>
    <mesh_term>Cystitis, Interstitial</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Somatoform Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Heparin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT04401176/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04401176
org study id: EKW_01-2020
nct id: NCT04401176
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Recognition of interstitial cystitis (IC)/bladder pain syndrome (BPS) is increasing. There is
      a dire need to develop effective treatment options for these patients as it manifests as more
      than a physical disease, affecting general and psychological health as well. Existing trials
      comparing varying bladder instillation formulations have not identified an optimal bladder
      instillation therapy, however existing studies support combined heparin and alkalinized
      lidocaine bladder instillation as an affordable and effective treatment for IC/BPS.
      Additionally, intradetrusor onabotulinumtoxinA injection has been well established for the
      treatment of overactive bladder (OAB), a constellation of symptoms similar to that of IC/BPS.
      OnabotulinumtoxinA has now come into the forefront for treatment of OAB due to its efficacy,
      safety profile, and absence of cognitive effects related to the previous mainstay
      anticholinergic treatment. While both bladder instillation and onabotulinumtoxinA therapy
      have been shown to be effective for treatment of IC/BPS, a direct comparison of these
      treatments has not been performed. We therefore designed a randomized controlled trial to
      compare the efficacy of heparin with alkalized local anesthetic bladder instillation versus
      intradetrusor onabotulinumtoxinA injection in treating IC/BPS symptoms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 8-10 weeks
description: Consists of O'Leary-Sant Symptom and Problem Index, total score 0-36.
measure: Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 6-9 months
description: Consists of O'Leary-Sant Symptom and Problem Index. Total score 0-36
measure: Change in pain scores using the Defense and Veterans Pain Rating Scale (visual analog scale) between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 8-10 weeks, 6-9 months
description: Scale of 0-10 (0= no pain, 10 = worst pain)
measure: Change in Female Sexual Function Index (FSFI) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 8-10 weeks
description: FSFI evaluates 5 domains of female sexual function including desire, arousal, lubrication, orgasm, satisfaction, and pain. Total score 2-36.
measure: Change in Female Sexual Distress Scale-Revised (FSDS-R) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 8-10 weeks
description: FSDS-R evaluates distress associated with inadequate/impaired sexual function. Total score 0-52.
measure: Change in 12-item Short Form Survey (SF-12) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 8-10 weeks
description: SF-12 is a general health questionnaire that evaluates quality of life measures, divided into mental and physical component scores.
measure: Change in bladder capacity between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: Baseline, 4-6 weeks, 8-10 weeks
description: Bladder capacity via 1-day bladder diary
measure: Incidence of adverse outcomes between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: 8-10 weeks
description: Adverse outcomes to be defined specific to medication administered (urinary tract infection in both bladder instillation and onabotulinumtoxinA injection groups, urinary retention requiring catheterization, systemic effects related to onabotulinumtoxinA group only)
measure: Patient perceptions of treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: 6-9 months
description: "How convenient or inconvenient was it to follow the treatment schedule as instructed?" (Scale 1-5 extremely inconvenient - extremely convenient) "How satisfied or dissatisfied are you in the ability of the treatment to treat your condition?" (Scale 1-5 extremely dissatisfied - extremely satisfied) "Taking all things into account, how satisfied or dissatisfied are you with this treatment?" (Scale 1-5 extremely dissatisfied - extremely satisfied) "How willing would you be to undergo this treatment again?" (Scale 1-5 extremely unwilling - extremely willing).
measure: Incidence of re-treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups
time frame: 6-9 months
description: Re-treatment defined as additional course or crossover treatment outside of assigned treatment group
arm group label: Heparin & Alkalinized Lidocaine Bladder Instillation
arm group type: Active Comparator
description: Six weekly bladder instillations, each instillation consisting of 40,000 IU Heparin, 200mg lidocaine, 2ml 8.4% sodium bicarbonate, sterile water for a total volume 50 milliliters (mL).
arm group label: Intradetrusor Onabotulinumtoxin A Injection
arm group type: Active Comparator
description: 100 units onabotulinumtoxinA reconstituted in 10mL of injectable saline, injected in 20 sites with 0.5mL per injection along the posterior wall of the bladder above the trigone.
intervention type: Drug
intervention name: Heparin & Alkalinized Lidocaine Bladder Instillation
description: Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void
arm group label: Heparin & Alkalinized Lidocaine Bladder Instillation
intervention type: Drug
intervention name: Onabotulinum Toxin A
description: Intradetrusor onabotulinumtoxinA injection (0.5mL x 20 sites)
arm group label: Intradetrusor Onabotulinumtoxin A Injection
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
url: https://www.auanet.org/guidelines/interstitial-cystitis-(ic/bps)-guideline
description: American Urological Association Interstitial Cystitis Guidelines
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citation: Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007 Sep;70(3):463-8. doi: 10.1016/j.urology.2007.04.038.
PMID: 17905097
citation: Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology. 2004 Nov;64(5):871-5; discussion 875. doi: 10.1016/j.urology.2004.06.073.
PMID: 15533466
citation: Giannantoni A, Costantini E, Di Stasi SM, Tascini MC, Bini V, Porena M. Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol. 2006 Apr;49(4):704-9. doi: 10.1016/j.eururo.2005.12.002. Epub 2006 Jan 4.
PMID: 16417964
citation: Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006 Apr;49(4):644-50. doi: 10.1016/j.eururo.2005.12.010. Epub 2006 Jan 4.
PMID: 16426734
citation: Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019 Aug 1;179(8):1084-1093. doi: 10.1001/jamainternmed.2019.0677.
PMID: 31233095
responsible party type: Sponsor
mesh term: Cystitis
mesh term: Cystitis, Interstitial
mesh term: Syndrome
mesh term: Somatoform Disorders
mesh term: Lidocaine
mesh term: Heparin
provided document: 