<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/NCT02239926</url>
  </required_header>
  <id_info>
    <org_study_id>14-000581</org_study_id>
    <nct_id>NCT02239926</nct_id>
  </id_info>
  <brief_title>Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With IBS-D</brief_title>
  <acronym>Ranolazine</acronym>
  <official_title>Effect of Ranolazine on Gastrointestinal Motor Function and Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Will Ranolazine improve bowel function and abdominal pain in human subjects with IBS-D?&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized double-blind placebo-controlled pilot study that will use validated&#xD;
      bowel questionnaires to evaluate the effects of ranolazine administered orally twice daily in&#xD;
      patients with diarrhea predominant IBS (IBS-D). The study will consist of a 2 week run in&#xD;
      period, followed by 4 weeks of treatment period with oral ranolazine 1000 mg twice daily.&#xD;
      Primary endpoint of the study will be the average Bowel Symptom Scale (BSS) scores for&#xD;
      diarrhea and adequate relief of IBS pain and discomfort are secondary end points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Difficulty in enrolling subjects&#xD;
  </why_stopped>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).</measure>
    <time_frame>baseline to 4 weeks</time_frame>
    <description>BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Abdominal Pain</measure>
    <time_frame>baseline to 4 weeks</time_frame>
    <description>Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Diarrhea Predominant Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Ranolazine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>tablet, 1000 mg twice daily for four weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranolazine</intervention_name>
    <description>On January 31, 2006, ranolazine was approved for use in the United States by the Food and Drug Administration (FDA) for the treatment of chronic angina pectoris.</description>
    <arm_group_label>Ranolazine</arm_group_label>
    <other_name>Trade name Ranexa by Gilead Sciences.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Males and non-pregnant, non-breastfeeding females with established diagnosis of IBS-D&#xD;
             by modified Rome III criteria (Abdominal Pain Intensity: weekly average of worst daily&#xD;
             score of &gt;3.0 on a 0 to 10 point scale and Stool Consistency: at least one stool with&#xD;
             a consistency of Type 5, 6 or 7 Bristol stool score on at least 2 days per week)&#xD;
&#xD;
          -  18-70 years old&#xD;
&#xD;
          -  U.S. resident&#xD;
&#xD;
          -  English-speaking (to provide consent and complete questionnaires)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Structural or metabolic diseases/conditions that affect the gastrointestinal system&#xD;
&#xD;
          -  Unable to withdraw the following medications 48 hours prior to the study:&#xD;
&#xD;
               -  Drugs that alter GI transit including Lomotil, and bile acid binders such as&#xD;
                  cholestyramine, prokinetics (e.g. metoclopramide, cisapride and erythromycin),&#xD;
                  narcotics (e.g. oxycodone, morphine) and anticholinergics (dicyclomine,&#xD;
                  hyoscyamine).&#xD;
&#xD;
               -  Analgesic drugs including narcotics, NSAID, cyclooxygenase-2 ( COX2) inhibitors&#xD;
                  (celecoxib, rofecoxib, and valdecoxib)&#xD;
&#xD;
               -  GABAergic agents (baclofen)&#xD;
&#xD;
               -  Benzodiazepines (e.g. lorazepam, alprazolam, and diazepam). Low stable doses of&#xD;
                  thyroid replacement, estrogen replacement, and low dose aspirin for&#xD;
                  cardioprotection and birth control pills or depot injections are permissible.&#xD;
&#xD;
          -  Unable to withdraw the following medications, which are contraindications of&#xD;
             ranolazine:&#xD;
&#xD;
               -  Strong Cytochrome P450, Family 3, Subfamily A (CYP3A) inhibitors (e.g.&#xD;
                  ketoconazole, clarithromycin, and nelfinavir)&#xD;
&#xD;
               -  CYP3A inducers (e.g. rifampin, phenobarbital, St. John's wort)&#xD;
&#xD;
          -  Female subjects who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Current symptoms of severe depression, as measured by Hospital Anxiety And Depression&#xD;
             Scale ( HADS) score greater than 15.&#xD;
&#xD;
          -  Clinical evidence (including physical exam, ECG, laboratory studies and review of the&#xD;
             medical history) of significant cardiovascular, respiratory, renal, hepatic,&#xD;
             gastrointestinal, hematological, neurological, psychiatric, or other disease that&#xD;
             interfere with the objectives of the study.&#xD;
&#xD;
          -  The Corrected QT Interval (QTc) &gt; 490 msec.&#xD;
&#xD;
          -  Active alcoholics not in remission or known substance abusers.&#xD;
&#xD;
          -  Liver cirrhosis&#xD;
&#xD;
          -  Patients with clinically significant hepatic disease.&#xD;
&#xD;
          -  Major cardiovascular events in the last 6 months.&#xD;
&#xD;
          -  Participation in another clinical trial (within 30 days).&#xD;
&#xD;
          -  Incarcerated.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuri A Saito, MD,MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <results_first_submitted>January 5, 2016</results_first_submitted>
  <results_first_submitted_qc>January 5, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 8, 2016</results_first_posted>
  <last_update_submitted>February 16, 2016</last_update_submitted>
  <last_update_submitted_qc>February 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Yuri A. Saito Loftus</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>IBS-D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were enrolled at Mayo Clinic, Rochester Minnesota.</recruitment_details>
      <pre_assignment_details>2 subjects were screen failures and were not randomized.&#xD;
1 subject signed informed consent, but the study was suspended prior to that subject's randomization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ranolazine</title>
          <description>tablet, 1000 mg twice daily for four weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ranolazine</title>
          <description>tablet, 1000 mg twice daily for four weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="2"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;=18 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Between 18 and 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).</title>
        <description>BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms.</description>
        <time_frame>baseline to 4 weeks</time_frame>
        <population>The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranolazine</title>
            <description>tablet, 1000 mg twice daily for four weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).</title>
          <description>BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms.</description>
          <population>The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Abdominal Pain</title>
        <description>Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours.</description>
        <time_frame>baseline to 4 weeks</time_frame>
        <population>The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranolazine</title>
            <description>tablet, 1000 mg twice daily for four weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Abdominal Pain</title>
          <description>Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours.</description>
          <population>The one subject who completed the study did not have complete data, so no analysis was performed. Study was terminated due to difficulty with enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Ranolazine</title>
          <description>tablet, 1000 mg twice daily for four weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated early due to enrollment issues.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Yuri Saito Loftus</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-255-3680</phone>
      <email>saito.yuri@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02239926
org study id: 14-000581
nct id: NCT02239926
lead sponsor: 
has dmc: No
Will Ranolazine improve bowel function and abdominal pain in human subjects with IBS-D?
This is a randomized double-blind placebo-controlled pilot study that will use validated
      bowel questionnaires to evaluate the effects of ranolazine administered orally twice daily in
      patients with diarrhea predominant IBS (IBS-D). The study will consist of a 2 week run in
      period, followed by 4 weeks of treatment period with oral ranolazine 1000 mg twice daily.
      Primary endpoint of the study will be the average Bowel Symptom Scale (BSS) scores for
      diarrhea and adequate relief of IBS pain and discomfort are secondary end points.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline in Diarrhea Using the Bowel Symptom Score (BSS).
time frame: baseline to 4 weeks
description: BSS is a 100-mm visual analog scale for each symptom of Irritable Bowel Syndrome (IBS) (pain or discomfort, bloating, and diarrhea) with an overall severity score. Lower scores indicate symptoms are not present and higher scores indicate severe symptoms.
measure: Mean Abdominal Pain
time frame: baseline to 4 weeks
description: Daily abdominal pain intensity was rated using an 11-point (0-10) numeric rating scale, with 0 being no pain, and 10 being the worst pain imaginable. Participants were asked to rate their worst abdominal pain over the past 24 hours.
arm group label: Ranolazine
arm group type: Active Comparator
description: tablet, 1000 mg twice daily for four weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Ranolazine
description: On January 31, 2006, ranolazine was approved for use in the United States by the Food and Drug Administration (FDA) for the treatment of chronic angina pectoris.
arm group label: Ranolazine
other name: Trade name Ranexa by Gilead Sciences.
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yuri A Saito, MD,MPH
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Yuri A. Saito Loftus
investigator title: Associate Professor of Medicine
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Diarrhea
mesh term: Ranolazine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated early due to enrollment issues.
point of contact: 