<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/NCT04450316</url>
  </required_header>
  <id_info>
    <org_study_id>57305</org_study_id>
    <nct_id>NCT04450316</nct_id>
  </id_info>
  <brief_title>Low-dose Naltrexone for Bladder Pain Syndrome</brief_title>
  <official_title>Low-dose Naltrexone for Bladder Pain Syndrome: A Randomized Placebo-controlled Prospective Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</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>
      Interstitial cystitis/Bladder Pain Syndrome (IC/PBS) is a constellation of symptoms of pelvic&#xD;
      discomfort that includes both bladder-related pain as well as urinary frequency, urgency, and&#xD;
      nocturia in the absence of an identifiable etiology that affects likely more than 5.4 million&#xD;
      patients in the United States. There is a significant overlap in patients with IC/PBS and&#xD;
      those with fibromyalgia and chronic pelvic pain syndrome. Low-dose naltrexone (LDN) has been&#xD;
      shown to be effective for the treatment of chronic pain conditions.&#xD;
&#xD;
      The primary aim of this study is to evaluate if LDN improves pain scores and lower urinary&#xD;
      tract symptoms in patients with IC/PBS. A secondary aim is to show that it has a low adverse&#xD;
      event profile.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>Randomized placebo-controlled pilot study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Participants will be randomized on a 1:1 ratio to either LDN or placebo. The randomization sequence will be logged by the study coordinator in a REDCap randomization log blinded to other research staff and clinical team and outcome assessors.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of subjects in the LDN and placebo groups that are responders with greater than 20% reductions in 7-day average of worst daily Numeric Rating Scale of Pain scores after 8 weeks of treatment.</measure>
    <time_frame>Will compare pre-intervention to week 8.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Brief Pain Inventory Score</measure>
    <time_frame>At pre-intervention to week 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average frequency and nocturia during a 5-day voiding diary</measure>
    <time_frame>At pre-intervention to week 8.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Bladder Pain/Interstitial Cystitis Symptom Score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in O'Leary Sant symptom scores</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in O'Leary Sant Problem Indices scores</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Global response assessment scale score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS pain behavior score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS physical function score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS sleep dysfunction score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS Sleep-Related Impairment</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS pain interference score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS fatigue score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS anxiety score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS depression score</measure>
    <time_frame>At pre-intervention to week 8</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Bladder Pain Syndrome</condition>
  <condition>Interstitial Cystitis</condition>
  <arm_group>
    <arm_group_label>Low-dose naltrexone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naltrexone</intervention_name>
    <description>4.5mg tab (low-dose) nightly</description>
    <arm_group_label>Low-dose naltrexone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 tab nightly</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women with non-Hunner and Hunner lesion disease&#xD;
&#xD;
          -  Meeting AUA definition of BPS: An unpleasant sensation (pain, pressure, discomfort)&#xD;
             perceived to be related to the urinary bladder associated with lower urinary tract&#xD;
             symptoms of greater than 6 weeks duration in the absence of infection or other&#xD;
             identifiable cause.&#xD;
&#xD;
          -  Stable treatment for 1 month&#xD;
&#xD;
          -  7-day maximum of pain scores at least 4/10 on the numerical rating scale of pain in&#xD;
             the bladder/pelvic area. Urinary frequency 8 or higher while awake. Nocturia 2 or&#xD;
             higher. BPIC-SS 19.&#xD;
&#xD;
          -  Agreement to not take opioids through the duration of the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Substance Use Disorder Diagnosis including Opioid Use Disorder Diagnosis&#xD;
&#xD;
          -  Known allergy to naltrexone or naloxone&#xD;
&#xD;
          -  Participation in another clinical trial&#xD;
&#xD;
          -  Current or planned pregnancy, or breastfeeding&#xD;
&#xD;
          -  Chronic pain in another location of the body that is more severe than that related to&#xD;
             BPS.&#xD;
&#xD;
          -  Any intravesical instillation in last 8 weeks&#xD;
&#xD;
          -  If on Elmiron, stable dose for last 3 months&#xD;
&#xD;
          -  If on amitriptyline, stable dose for last 3 months&#xD;
&#xD;
          -  Any botox within last 6 months&#xD;
&#xD;
          -  Treatment for Hunners in the last 6 months&#xD;
&#xD;
          -  Any new Interstim settings within last 3 months&#xD;
&#xD;
          -  Any new pelvic floor physical therapy in last 12 weeks&#xD;
&#xD;
          -  Any change in or new OTC meds over last 2 months.&#xD;
&#xD;
          -  Any pain interventions in the preceding 6 weeks (epidural steroid injection,&#xD;
             sympathetic block, peripheral nerve block, lumbar medial branch blocks)&#xD;
&#xD;
          -  Opioids chronically for IC/BPS in the past unless have been off for 1 year&#xD;
&#xD;
          -  Recent short-term (within one week of enrollment) opioid use for flairs&#xD;
&#xD;
          -  No documented cystoscopy in the last 5 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig V Comiter, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Phil Hanno, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jennifer M Hah, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gabrielle Hettie</last_name>
    <phone>650-724-2091</phone>
    <email>bhettie@stanford.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford Health Care</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gabrielle Hettie</last_name>
      <phone>650-724-2091</phone>
      <email>bhettie@stanford.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.</citation>
    <PMID>24526250</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>July 7, 2022</last_update_submitted>
  <last_update_submitted_qc>July 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Jennifer Hah</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </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>Naltrexone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Should the study result be positive or promising, we would undertake a larger trial at which point we can reassess the sharing of IPD.</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/NCT04450316
org study id: 57305
nct id: NCT04450316
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Interstitial cystitis/Bladder Pain Syndrome (IC/PBS) is a constellation of symptoms of pelvic
      discomfort that includes both bladder-related pain as well as urinary frequency, urgency, and
      nocturia in the absence of an identifiable etiology that affects likely more than 5.4 million
      patients in the United States. There is a significant overlap in patients with IC/PBS and
      those with fibromyalgia and chronic pelvic pain syndrome. Low-dose naltrexone (LDN) has been
      shown to be effective for the treatment of chronic pain conditions.

      The primary aim of this study is to evaluate if LDN improves pain scores and lower urinary
      tract symptoms in patients with IC/PBS. A secondary aim is to show that it has a low adverse
      event profile.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized placebo-controlled pilot study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Participants will be randomized on a 1:1 ratio to either LDN or placebo. The randomization sequence will be logged by the study coordinator in a REDCap randomization log blinded to other research staff and clinical team and outcome assessors.
measure: The proportion of subjects in the LDN and placebo groups that are responders with greater than 20% reductions in 7-day average of worst daily Numeric Rating Scale of Pain scores after 8 weeks of treatment.
time frame: Will compare pre-intervention to week 8.
measure: Change in Brief Pain Inventory Score
time frame: At pre-intervention to week 8.
measure: Change in average frequency and nocturia during a 5-day voiding diary
time frame: At pre-intervention to week 8.
measure: Change in Bladder Pain/Interstitial Cystitis Symptom Score
time frame: At pre-intervention to week 8
measure: Change in O'Leary Sant symptom scores
time frame: At pre-intervention to week 8
measure: Change in O'Leary Sant Problem Indices scores
time frame: At pre-intervention to week 8
measure: Change in Global response assessment scale score
time frame: At pre-intervention to week 8
measure: Change in PROMIS pain behavior score
time frame: At pre-intervention to week 8
measure: Change in PROMIS physical function score
time frame: At pre-intervention to week 8
measure: Change in PROMIS sleep dysfunction score
time frame: At pre-intervention to week 8
measure: Change in PROMIS Sleep-Related Impairment
time frame: At pre-intervention to week 8
measure: Change in PROMIS pain interference score
time frame: At pre-intervention to week 8
measure: Change in PROMIS fatigue score
time frame: At pre-intervention to week 8
measure: Change in PROMIS anxiety score
time frame: At pre-intervention to week 8
measure: Change in PROMIS depression score
time frame: At pre-intervention to week 8
arm group label: Low-dose naltrexone
arm group type: Active Comparator
description: 4.5mg of naltrexone to be taken one hour prior to bedtime nightly for 8 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo tablet (sugar-pill) to be taken one hour prior to bedtime nightly for 8 weeks.
intervention type: Drug
intervention name: Naltrexone
description: 4.5mg tab (low-dose) nightly
arm group label: Low-dose naltrexone
intervention type: Drug
intervention name: Placebo
description: 1 tab nightly
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Craig V Comiter, MD
role: Principal Investigator
affiliation: Stanford University
last name: Phil Hanno, MD
role: Principal Investigator
affiliation: Stanford University
last name: Jennifer M Hah, MD, MS
role: Principal Investigator
affiliation: Stanford University
last name: Gabrielle Hettie
phone: 650-724-2091
email: bhettie@stanford.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.
PMID: 24526250
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Jennifer Hah
investigator title: Assistant Professor
mesh term: Cystitis
mesh term: Cystitis, Interstitial
mesh term: Syndrome
mesh term: Somatoform Disorders
mesh term: Naltrexone
sharing ipd: No
ipd description: Should the study result be positive or promising, we would undertake a larger trial at which point we can reassess the sharing of IPD.