<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/NCT03270085</url>
  </required_header>
  <id_info>
    <org_study_id>17-004639</org_study_id>
    <secondary_id>R01DK115950</secondary_id>
    <secondary_id>UL1TR000135</secondary_id>
    <nct_id>NCT03270085</nct_id>
  </id_info>
  <brief_title>Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption</brief_title>
  <official_title>Randomized, Double Blinded, Placebo Controlled Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare with a randomized trial (n=15 per treatment group), effects of colesevelam and&#xD;
      placebo treatment, on colonic transit, bowel functions, permeability and tight junction&#xD;
      expression in rectosigmoid mucosa of IBS-D with Bile Acid Malabsorption.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Compare the effects of Colesevelam versus the placebo on diabetic subjects with chronic&#xD;
      diarrhea. In this study, diabetic subjects will get either the Colesevelam or the placebo,&#xD;
      not both.&#xD;
&#xD;
      The plan is to have about 30 subjects complete this study at Mayo Clinic.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">May 31, 2019</completion_date>
  <primary_completion_date type="Actual">May 31, 2019</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 the third specific aim of a program on IBS-D with increased fecal bile acid excretion.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>30 subjects with irritable bowel syndrome and diarrhea and bile acid malabsorption will be randomized into 15 people per group in 4-week double-blind, parallel-group trial to Colesevelam or placebo.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Total Fecal Bile Acid (BA) Excretion</measure>
    <time_frame>Treatment day 28</time_frame>
    <description>Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stool Consistency</measure>
    <time_frame>Treatment days 1 through 28</time_frame>
    <description>Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Stools Per Day</measure>
    <time_frame>Treatment days 1 through 28</time_frame>
    <description>The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Chronic Diarrhea</condition>
  <condition>Irritable Bowel Syndrome With Diarrhea</condition>
  <condition>Bile Acid Malabsorption</condition>
  <arm_group>
    <arm_group_label>Colesevelam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing period consists of: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, and medication pick up.&#xD;
Treatment period will have subject take the study drug 1875 mg of medication orally twice daily with lunch and supper for 4-5 weeks.&#xD;
The last period, is the treatment testing period. This consists of a full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
The last period, is the treatment testing period. This consists of a full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colesevelam</intervention_name>
    <description>Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
    <arm_group_label>Colesevelam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females and males age 18 -75.&#xD;
&#xD;
          -  An IBS diagnosis based on the Rome III criteria for at least 3 months, with onset at&#xD;
             least 6 months previously, of recurrent abdominal pain or discomfort.&#xD;
&#xD;
          -  Biomarkers serum alpha C4 ≥ 40 ng/mL or FGF19 ≤ 80 pg/mL or fecal bile acid &gt;2000&#xD;
             micromoles/48h&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  IBS patients with known clinically-relevant inflammation.&#xD;
&#xD;
          -  IBS patient with known bleeding diathesis&#xD;
&#xD;
          -  History of abdominal surgery&#xD;
&#xD;
        Patients participating will not take any of the following disallowed medications for at&#xD;
        least 7 days prior to and during the remainder of the study:&#xD;
&#xD;
          -  Any treatment specifically taken for IBS-D, including loperamide, cholestyramine,&#xD;
             alosetron&#xD;
&#xD;
          -  Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors&#xD;
&#xD;
          -  All narcotics&#xD;
&#xD;
          -  Anti-cholinergic agents&#xD;
&#xD;
          -  Tramadol&#xD;
&#xD;
          -  Oral anticoagulants&#xD;
&#xD;
          -  Antimuscarinics&#xD;
&#xD;
          -  Peppermint oil&#xD;
&#xD;
          -  Systemic antibiotics, as well as antibiotics directed at colonic flora such as&#xD;
             rifaximin and metronidazole&#xD;
&#xD;
        Gastrointestinal preparations:&#xD;
&#xD;
          -  Anti-nausea agents&#xD;
&#xD;
          -  Osmotic laxative agents&#xD;
&#xD;
          -  Prokinetic agents&#xD;
&#xD;
          -  5-HT3 antagonists&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Camilleri</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>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <results_reference>
    <citation>Vijayvargiya P, Camilleri M, Carlson P, Nair A, Nord SL, Ryks M, Rhoten D, Burton D, Busciglio I, Lueke A, Harmsen WS, Donato LJ. Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2962-2970.e6. doi: 10.1016/j.cgh.2020.02.027. Epub 2020 Feb 21.</citation>
    <PMID>32088296</PMID>
  </results_reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <results_first_submitted>April 14, 2020</results_first_submitted>
  <results_first_submitted_qc>April 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 27, 2020</results_first_posted>
  <last_update_submitted>April 14, 2020</last_update_submitted>
  <last_update_submitted_qc>April 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Michael Camilleri, MD</investigator_full_name>
    <investigator_title>Michael Camilleri, M.D. Professor of Medicine, Pharmacology and Physiology, Atherton and Winifred W. Bean Professor, College of Medicine Consultant, Division of Gastroenterology and Hepatology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Malabsorption Syndromes</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colesevelam Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03270085/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Colesevelam</title>
          <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Colesevelam</title>
          <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</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="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44" lower_limit="34" upper_limit="52"/>
                    <measurement group_id="B2" value="56" lower_limit="40" upper_limit="68"/>
                    <measurement group_id="B3" value="50" lower_limit="34" upper_limit="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.2" lower_limit="28.0" upper_limit="37.6"/>
                    <measurement group_id="B2" value="33.6" lower_limit="28.2" upper_limit="36.4"/>
                    <measurement group_id="B3" value="33.4" lower_limit="28.0" upper_limit="36.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Fecal Bile Acid (BA) Excretion</title>
        <description>Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool.</description>
        <time_frame>Treatment day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Colesevelam</title>
            <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Fecal Bile Acid (BA) Excretion</title>
          <description>Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool.</description>
          <units>μmoles/g</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.7" lower_limit="8.2" upper_limit="17.4"/>
                    <measurement group_id="O2" value="3.6" lower_limit="2.6" upper_limit="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Stool Consistency</title>
        <description>Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period.</description>
        <time_frame>Treatment days 1 through 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Colesevelam</title>
            <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
          </group>
        </group_list>
        <measure>
          <title>Stool Consistency</title>
          <description>Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" lower_limit="3.9" upper_limit="5.2"/>
                    <measurement group_id="O2" value="4.6" lower_limit="4.3" upper_limit="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.81</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Stools Per Day</title>
        <description>The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period.</description>
        <time_frame>Treatment days 1 through 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Colesevelam</title>
            <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Stools Per Day</title>
          <description>The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period.</description>
          <units>number of stools per day</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" lower_limit="1.6" upper_limit="3.8"/>
                    <measurement group_id="O2" value="2.2" lower_limit="1.6" upper_limit="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.91</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for each subject from baseline to the end of the study, approximately 10 weeks, for a total study duration of approximately 18 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Colesevelam</title>
          <description>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Baseline testing: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.&#xD;
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.&#xD;
Colesevelam: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.&#xD;
Treatment testing period: full transit &amp; urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.&#xD;
Placebo: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </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>
    <point_of_contact>
      <name_or_title>Michael Camilleri, MD</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-266-2305</phone>
      <email>camilleri.michael@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/NCT03270085
org study id: 17-004639
secondary id: R01DK115950
secondary id: UL1TR000135
nct id: NCT03270085
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To compare with a randomized trial (n=15 per treatment group), effects of colesevelam and
      placebo treatment, on colonic transit, bowel functions, permeability and tight junction
      expression in rectosigmoid mucosa of IBS-D with Bile Acid Malabsorption.
Compare the effects of Colesevelam versus the placebo on diabetic subjects with chronic
      diarrhea. In this study, diabetic subjects will get either the Colesevelam or the placebo,
      not both.

      The plan is to have about 30 subjects complete this study at Mayo Clinic.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is the third specific aim of a program on IBS-D with increased fecal bile acid excretion.
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
masking description: 30 subjects with irritable bowel syndrome and diarrhea and bile acid malabsorption will be randomized into 15 people per group in 4-week double-blind, parallel-group trial to Colesevelam or placebo.
measure: Total Fecal Bile Acid (BA) Excretion
time frame: Treatment day 28
description: Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool.
measure: Stool Consistency
time frame: Treatment days 1 through 28
description: Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period.
measure: Number of Stools Per Day
time frame: Treatment days 1 through 28
description: The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period.
arm group label: Colesevelam
arm group type: Active Comparator
description: Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks.
Baseline testing period consists of: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, and medication pick up.
Treatment period will have subject take the study drug 1875 mg of medication orally twice daily with lunch and supper for 4-5 weeks.
The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.
arm group label: Placebo
arm group type: Placebo Comparator
description: Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks.
The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.
intervention type: Drug
intervention name: Colesevelam
description: Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.
arm group label: Colesevelam
intervention type: Other
intervention name: Placebo
description: A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Michael Camilleri
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
citation: Vijayvargiya P, Camilleri M, Carlson P, Nair A, Nord SL, Ryks M, Rhoten D, Burton D, Busciglio I, Lueke A, Harmsen WS, Donato LJ. Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2962-2970.e6. doi: 10.1016/j.cgh.2020.02.027. Epub 2020 Feb 21.
PMID: 32088296
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Michael Camilleri, MD
investigator title: Michael Camilleri, M.D. Professor of Medicine, Pharmacology and Physiology, Atherton and Winifred W. Bean Professor, College of Medicine Consultant, Division of Gastroenterology and Hepatology
mesh term: Irritable Bowel Syndrome
mesh term: Malabsorption Syndromes
mesh term: Diarrhea
mesh term: Colesevelam Hydrochloride
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 