<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/NCT04456517</url>
  </required_header>
  <id_info>
    <org_study_id>200640</org_study_id>
    <nct_id>NCT04456517</nct_id>
  </id_info>
  <brief_title>Reduce Crohn's-Associated Diarrhea With Sodium Channel Therapy</brief_title>
  <acronym>REACT</acronym>
  <official_title>REACT Trial: A Randomized, Double Blind, Placebo-controlled, Crossover Study of Ranolazine for the Treatment of Crohn's Disease-associated Diarrhea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Crohn's disease is an inflammatory disorder that can affect any part of the gastrointestinal&#xD;
      (GI) tract. Some patients still experience persistent diarrhea or other symptoms such as&#xD;
      abdominal pain even when their Crohn's disease is in remission. Diarrhea and/or abdominal&#xD;
      pain that is not responsive to standard therapies can significantly affect a patient's&#xD;
      quality of life and ability to work. The purpose of this study is to test the safety and&#xD;
      effectiveness of the drug ranolazine in reducing Crohn's disease-associated diarrhea and&#xD;
      other symptoms. Ranolazine is approved by the US Food &amp; Drug Administration (FDA) for chronic&#xD;
      angina (a heart condition). This study is investigating if ranolazine could be used in the&#xD;
      setting of Crohn's disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">October 18, 2022</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2025</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Participants receive one of two alternative interventions during the initial phase of the study and receive the other intervention during the second phase of the study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in daily number of loose stools from baseline</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>Daily number of loose stools and antidiarrheal use will be collected directly from all subjects using MyCap or, if installation and use of an app is not possible, through email with a survey link. MyCap is a secure mobile application developed by the REDCap team at Vanderbilt and integrated into the REDCap database system.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in Crohn's Disease Activity Index (CDAI) score</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>The Crohn's Disease Activity Index (CDAI) combines weighted scores of clinical and laboratory variables to estimate disease severity. The CDAI consists of eight variables, two of which are subjective, related to the disease, each weighted according to its ability to be predictive of disease activity. The absolute score ranges from 0 to 600. CDAI scores of less than 150 indicate a clinical remission and scores over 450 indicate severely active disease. Since blood draws will not be performed as part of this study, the hematocrit component of the CDAI will not be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Harvey Bradshaw Index (HBI) score</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>The Harvey-Bradshaw index (Harvey-Bradshaw Index - HBI) assesses the degree of illness (activity) in patients with Crohn's disease. The HBI consists of 5 items with a minimum score of 0 and a maximum attainable score depending on the number of stools the patient identifies per day. HBI scores &lt; 5 are defined as clinical remission, HBI between 5 and 7 as mild disease, HBI between 8 and 16 as moderate disease, and HBI &gt; 16 as severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score</measure>
    <time_frame>Baseline, Day 84, and Day 168</time_frame>
    <description>The SIBDQ is a 10-item questionnaire measuring quality of life in four domains: bowel symptoms, emotional health, systemic symptoms, and social function and is scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). The absolute score ranges are from 10 (poor Health-related quality of life) to 70 (optimum Health-related quality of life).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Health Questionnaire (PHQ-9) score</measure>
    <time_frame>Baseline, Day 84, Day 168</time_frame>
    <description>The PHQ-9 is a 9-item questionnaire that screens for the presence and severity of depression and can be used to make a depression diagnosis using DSM-IV criteria.&#xD;
The PHQ-9 is scored on a 3-point Likert scale from 0 (not at all) to 3 (nearly every day). The absolute score ranges are from 0 (none or minimal depression) to 27 (severe depression).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">16</enrollment>
  <condition>Crohn's Disease</condition>
  <condition>Inflammatory Bowel Disease</condition>
  <arm_group>
    <arm_group_label>Ranolazine, Then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- Participants first receive a Ranolazine 500 mg tablet twice daily for 12 weeks, they then receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Then Ranolazine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- Participants first receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks, they then receive a Ranolazine 500mg tablet twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranolazine</intervention_name>
    <description>500 mg tablet</description>
    <arm_group_label>Placebo, Then Ranolazine</arm_group_label>
    <arm_group_label>Ranolazine, Then Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Ranolazine-matched placebo tablet</description>
    <arm_group_label>Placebo, Then Ranolazine</arm_group_label>
    <arm_group_label>Ranolazine, Then Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meet diagnostic criteria for Crohn's Disease with active diarrhea Either with active&#xD;
             disease or in remission (as defined by endoscopic or radiographic findings) but&#xD;
             experiencing symptoms (e.g., diarrhea, abdominal pain)&#xD;
&#xD;
          -  Have greater than three loose stools per day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects &lt;18 years of age&#xD;
&#xD;
          -  Significant change in medication including prednisone, antidepressant medications, or&#xD;
             stimulants within the last 4 weeks&#xD;
&#xD;
             a. Allowances include: Rectal hydrocortisone, rectal mesalamine, addition of&#xD;
             prednisone (up to 20mg) for flares, etc.&#xD;
&#xD;
          -  Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or&#xD;
             marijuana use&#xD;
&#xD;
          -  Severe psychiatric disease including schizophrenia, psychosis, suicidal depression&#xD;
&#xD;
          -  Previous use of ranolazine within 2 months prior to enrollment&#xD;
&#xD;
          -  Prior use of ranolazine which was discontinued for safety or tolerability&#xD;
&#xD;
          -  Metabolic derangement defined as liver function tests &gt;3x upper limit of normal or&#xD;
             severe renal disease defined as calculated creatinine clearance &lt;30 mL/min&#xD;
&#xD;
          -  Have liver cirrhosis&#xD;
&#xD;
          -  Concurrent use of CYP3A inhibitors, inducers, or substrates&#xD;
&#xD;
             a. These may include: ketoconazole, itraconazole, clarithromycin, nefazodone,&#xD;
             nelfinavir, ritonavir, indinavir, and saquinavir, diltiazem, verapamil, erythromycin,&#xD;
             fluconazole, grapefruit juice or grapefruit-containing products, rifampin, rifabutin,&#xD;
             rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's Wort.&#xD;
&#xD;
          -  Concurrent use of statin medications, Digoxine, TCA antidepressants or&#xD;
             anti-psychotics, or metformin&#xD;
&#xD;
          -  Concurrent use of OCT2 substrates&#xD;
&#xD;
          -  Concurrent use of drugs transported by P-gp or drugs metabolized by CYP2D6&#xD;
&#xD;
          -  Concurrent use of drugs known to prolong the QT interval&#xD;
&#xD;
          -  A family history of (or congenital) long QT syndrome or known acquired QT interval&#xD;
             prolongation&#xD;
&#xD;
          -  Inability or refusal to give informed consent for any reason including a diagnosis of&#xD;
             dementia or cognitive impairment&#xD;
&#xD;
          -  Patients who are pregnant or breastfeeding&#xD;
&#xD;
          -  Patients who are enrolled in other investigational drug studies or who have taken&#xD;
             investigational drugs within 30 days before enrollment&#xD;
&#xD;
          -  Other factors which in the opinion of the investigator could potentially impact the&#xD;
             study outcomes (e.g., underlying disease, medications, history) or prevent the&#xD;
             participant from completing the protocol (poor compliance or unpredictable schedule)&#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>Dawn B. Beaulieu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>October 21, 2022</last_update_submitted>
  <last_update_submitted_qc>October 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Dawn Beaulieu</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>Diarrhea</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranolazine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The investigators agree to the timely release and sharing of information to be no later than the acceptance for publication of the main findings from the final data set. Investigators are also committed to ensuring that all data are free of identifiers that would permit linkage to individual research participation as well as variables that could lead to deductive disclosure of individual subjects.</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/NCT04456517
org study id: 200640
nct id: NCT04456517
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Crohn's disease is an inflammatory disorder that can affect any part of the gastrointestinal
      (GI) tract. Some patients still experience persistent diarrhea or other symptoms such as
      abdominal pain even when their Crohn's disease is in remission. Diarrhea and/or abdominal
      pain that is not responsive to standard therapies can significantly affect a patient's
      quality of life and ability to work. The purpose of this study is to test the safety and
      effectiveness of the drug ranolazine in reducing Crohn's disease-associated diarrhea and
      other symptoms. Ranolazine is approved by the US Food & Drug Administration (FDA) for chronic
      angina (a heart condition). This study is investigating if ranolazine could be used in the
      setting of Crohn's disease.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Participants receive one of two alternative interventions during the initial phase of the study and receive the other intervention during the second phase of the study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean change in daily number of loose stools from baseline
time frame: Baseline to Week 36
description: Daily number of loose stools and antidiarrheal use will be collected directly from all subjects using MyCap or, if installation and use of an app is not possible, through email with a survey link. MyCap is a secure mobile application developed by the REDCap team at Vanderbilt and integrated into the REDCap database system.
measure: Mean change in Crohn's Disease Activity Index (CDAI) score
time frame: Baseline to Week 36
description: The Crohn's Disease Activity Index (CDAI) combines weighted scores of clinical and laboratory variables to estimate disease severity. The CDAI consists of eight variables, two of which are subjective, related to the disease, each weighted according to its ability to be predictive of disease activity. The absolute score ranges from 0 to 600. CDAI scores of less than 150 indicate a clinical remission and scores over 450 indicate severely active disease. Since blood draws will not be performed as part of this study, the hematocrit component of the CDAI will not be assessed.
measure: Mean change in Harvey Bradshaw Index (HBI) score
time frame: Baseline to Week 36
description: The Harvey-Bradshaw index (Harvey-Bradshaw Index - HBI) assesses the degree of illness (activity) in patients with Crohn's disease. The HBI consists of 5 items with a minimum score of 0 and a maximum attainable score depending on the number of stools the patient identifies per day. HBI scores < 5 are defined as clinical remission, HBI between 5 and 7 as mild disease, HBI between 8 and 16 as moderate disease, and HBI > 16 as severe disease.
measure: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score
time frame: Baseline, Day 84, and Day 168
description: The SIBDQ is a 10-item questionnaire measuring quality of life in four domains: bowel symptoms, emotional health, systemic symptoms, and social function and is scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). The absolute score ranges are from 10 (poor Health-related quality of life) to 70 (optimum Health-related quality of life).
measure: Patient Health Questionnaire (PHQ-9) score
time frame: Baseline, Day 84, Day 168
description: The PHQ-9 is a 9-item questionnaire that screens for the presence and severity of depression and can be used to make a depression diagnosis using DSM-IV criteria.
The PHQ-9 is scored on a 3-point Likert scale from 0 (not at all) to 3 (nearly every day). The absolute score ranges are from 0 (none or minimal depression) to 27 (severe depression).
arm group label: Ranolazine, Then Placebo
arm group type: Experimental
description: - Participants first receive a Ranolazine 500 mg tablet twice daily for 12 weeks, they then receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms
arm group label: Placebo, Then Ranolazine
arm group type: Experimental
description: - Participants first receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks, they then receive a Ranolazine 500mg tablet twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms
intervention type: Drug
intervention name: Ranolazine
description: 500 mg tablet
arm group label: Placebo, Then Ranolazine
arm group label: Ranolazine, Then Placebo
intervention type: Drug
intervention name: Placebo
description: Ranolazine-matched placebo tablet
arm group label: Placebo, Then Ranolazine
arm group label: Ranolazine, Then Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dawn B. Beaulieu, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Dawn Beaulieu
investigator title: Principle Investigator
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
mesh term: Diarrhea
mesh term: Ranolazine
sharing ipd: Yes
ipd description: The investigators agree to the timely release and sharing of information to be no later than the acceptance for publication of the main findings from the final data set. Investigators are also committed to ensuring that all data are free of identifiers that would permit linkage to individual research participation as well as variables that could lead to deductive disclosure of individual subjects.