<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/NCT02978339</url>
  </required_header>
  <id_info>
    <org_study_id>14-002660</org_study_id>
    <nct_id>NCT02978339</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis (PSC)</brief_title>
  <official_title>An Open-Label Pilot Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>John E. Eaton</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>EuroPharma, Inc.</agency>
      <agency_class>Industry</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>
      The purpose of this study is to determine whether curcumin, a drug and naturally-occurring&#xD;
      plant compound, is safe and effective in the treatment of primary sclerosing cholangitis&#xD;
      (PSC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2017</start_date>
  <completion_date type="Actual">January 8, 2019</completion_date>
  <primary_completion_date type="Actual">November 16, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Serum Alkaline Phosphatase (SAP)</measure>
    <time_frame>baseline, 12 weeks</time_frame>
    <description>Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Aspartate Aminotransferase (AST)</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total Bilirubin</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in C-Reactive Protein (CRP)</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:&#xD;
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fatigue Severity</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Pruritus</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials.&quot; The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Primary Sclerosing Cholangitis</condition>
  <arm_group>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Curcumin</intervention_name>
    <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
    <arm_group_label>Curcumin</arm_group_label>
    <other_name>CuraMed® softgel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of primary sclerosing cholangitis (PSC) established by all of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Alkaline phosphatase &gt;1.5x upper limit of normal for at least 6 months prior to&#xD;
                  study enrollment&#xD;
&#xD;
               -  Cholangiography demonstrating intrahepatic and/or extrahepatic biliary dilation,&#xD;
                  beading, and/or strictures consistent with PSC&#xD;
&#xD;
               -  Liver histology (if available for review) consistent with or diagnostic of PSC&#xD;
&#xD;
          -  Women of child-bearing potential willing to use birth control for the duration of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with any investigational agents within three months prior to or during the&#xD;
             study&#xD;
&#xD;
          -  Treatment with systemic antibiotics, azulfidine, systemic corticosteroids, colchicine,&#xD;
             methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline,&#xD;
             tacrolimus, or vitamin E within three months prior to or during the study.&#xD;
&#xD;
          -  Concomitant treatment with NSAIDS, antiplatelet agents, antihyperlipidemics, and&#xD;
             anticoagulant warfarin.&#xD;
&#xD;
          -  Anticipated need for liver transplant within one year as determined by Mayo PSC risk&#xD;
             score (&lt;80% one-year survival without transplant)&#xD;
&#xD;
          -  Active drug or alcohol use&#xD;
&#xD;
          -  Findings suggestive of liver disease of an alternative or concomitant etiology, such&#xD;
             as chronic alcoholic liver disease, chronic hepatitis B or C infection,&#xD;
             hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, non-alcoholic&#xD;
             steatohepatitis, primary biliary cirrhosis, or secondary sclerosing cholangitis (e.g.,&#xD;
             post-liver transplantation biliary stricture)&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would interfere with the&#xD;
             patient's ability to complete the study safely or successfully.&#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>Nicholas F LaRusso, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905-0001</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>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <results_first_submitted>December 13, 2019</results_first_submitted>
  <results_first_submitted_qc>January 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 18, 2020</results_first_posted>
  <last_update_submitted>January 7, 2020</last_update_submitted>
  <last_update_submitted_qc>January 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>John E. Eaton</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangitis</mesh_term>
    <mesh_term>Cholangitis, Sclerosing</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Curcumin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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>January 3, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT02978339/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Curcumin</title>
          <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</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_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Curcumin</title>
          <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46" lower_limit="39" upper_limit="57"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Sclerosing Cholangitis Duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.00" lower_limit="4" upper_limit="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Inflammatory Bowel Disease Present</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Serum Alkaline Phosphatase (SAP)</title>
        <description>Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.</description>
        <time_frame>baseline, 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Alkaline Phosphatase (SAP)</title>
          <description>Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.03</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Aspartate Aminotransferase (AST)</title>
        <description>AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Aspartate Aminotransferase (AST)</title>
          <description>AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)</description>
          <units>U/L</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78" lower_limit="48" upper_limit="119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.59</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Bilirubin</title>
        <description>Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Bilirubin</title>
          <description>Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)</description>
          <units>mg/dL</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.5" upper_limit="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.91</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in C-Reactive Protein (CRP)</title>
        <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in C-Reactive Protein (CRP)</title>
          <description>C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)</description>
          <units>mg/L</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" lower_limit="1.5" upper_limit="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.41</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score</title>
        <description>The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:&#xD;
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Twelve subjects completed questionnaires. Three subjects did not complete questionnaires</population>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score</title>
          <description>The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:&#xD;
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.</description>
          <population>Twelve subjects completed questionnaires. Three subjects did not complete questionnaires</population>
          <units>score 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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" lower_limit="-0.17" upper_limit="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.15</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fatigue Severity</title>
        <description>Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Twelve subjects completed questionnaires. Three subjects did not complete questionnaires.</population>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fatigue Severity</title>
          <description>Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.</description>
          <population>Twelve subjects completed questionnaires. Three subjects did not complete questionnaires.</population>
          <units>score 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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.00" lower_limit="4.00" upper_limit="23.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.06</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Pruritus</title>
        <description>Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials.&quot; The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>Twelve of the subjects completed questionnaires. Three subjects did not complete questionnaires</population>
        <group_list>
          <group group_id="O1">
            <title>Curcumin</title>
            <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pruritus</title>
          <description>Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials.&quot; The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)</description>
          <population>Twelve of the subjects completed questionnaires. Three subjects did not complete questionnaires</population>
          <units>score 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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.00" lower_limit="7.50" upper_limit="14.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.93</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected for 12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Curcumin</title>
          <description>Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.&#xD;
Curcumin: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.</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"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" 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>John E. Eaton, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-284-3917</phone>
      <email>Eaton.John@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/NCT02978339
org study id: 14-002660
nct id: NCT02978339
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether curcumin, a drug and naturally-occurring
      plant compound, is safe and effective in the treatment of primary sclerosing cholangitis
      (PSC).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Serum Alkaline Phosphatase (SAP)
time frame: baseline, 12 weeks
description: Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.
measure: Change in Serum Aspartate Aminotransferase (AST)
time frame: Baseline, 12 weeks
description: AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)
measure: Change in Total Bilirubin
time frame: Baseline, 12 weeks
description: Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)
measure: Change in C-Reactive Protein (CRP)
time frame: Baseline, 12 weeks
description: C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)
measure: Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score
time frame: Baseline, 12 weeks
description: The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.
measure: Change in Fatigue Severity
time frame: Baseline, 12 weeks
description: Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.
measure: Change in Pruritus
time frame: Baseline, 12 weeks
description: Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials." The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)
arm group label: Curcumin
arm group type: Experimental
description: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.
intervention type: Drug
intervention name: Curcumin
description: Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.
arm group label: Curcumin
other name: CuraMed® softgel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Nicholas F LaRusso, M.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: John E. Eaton
investigator title: Principal Investigator
mesh term: Cholangitis
mesh term: Cholangitis, Sclerosing
mesh term: Curcumin
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 