<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/NCT02246647</url>
  </required_header>
  <id_info>
    <org_study_id>14-002382</org_study_id>
    <nct_id>NCT02246647</nct_id>
  </id_info>
  <brief_title>Biomarkers for Intestinal Permeability in Patients With Constipation</brief_title>
  <official_title>Biomarkers for Intestinal Permeability in Patients With Functional Lower Gastrointestinal Disorders Associated With Constipation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda Pharmaceuticals International, 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>
      Our overall objective with this study is firstly to provide a comprehensive assessment of&#xD;
      intestinal permeability, mucosal barrier function using existing biomarkers and secondly to&#xD;
      explore novel biomarkers for measuring intestinal permeability in patients with constipation&#xD;
      predominant Irritable Bowel Syndrome (IBS-C).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In order to determine the differences in permeability in IBS-C in comparison with healthy&#xD;
      volunteers, the following will be determined: differences in in vivo small intestinal and&#xD;
      colonic permeability, differences in small intestinal and colonic mucosal barrier function,&#xD;
      differences in effects of fecal supernatants on barrier function of T84 monolayers, and&#xD;
      differences in novel biomarkers for intestinal permeability&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 8, 2016</completion_date>
  <primary_completion_date type="Actual">December 8, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.</measure>
    <time_frame>8-24 hr post test-dose administration</time_frame>
    <description>In vivo measurement of intestinal permeability using 13C mannitol &amp; lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lactose:C13 Mannitol Excretion Ratio 0-2hours</measure>
    <time_frame>0-2 hr post-test dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa</measure>
    <time_frame>3 hours post FITC-Dextran (4kDa) administration</time_frame>
    <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa</measure>
    <time_frame>Over 3 hours post FITC-Dextran (4kDa) administration</time_frame>
    <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline Transmucosal Resistance (TMR) of Colonic Mucosa</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa</measure>
    <time_frame>3 hours post FITC-Dextran (4kDa) administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa</measure>
    <time_frame>Over 3 hours post FITC-Dextran (4kDa) administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa</measure>
    <time_frame>3 hours post E.coli Bio- Particle administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa</measure>
    <time_frame>Over 3 hours post E.coli Bio- Particle administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa</measure>
    <time_frame>3 hours post E.coli Bio- Particle administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa</measure>
    <time_frame>Over 3 hours post E.coli Bio- Particle administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duodenal Impedance</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Serum Endotoxin (Bacterial LPS) Levels</measure>
    <time_frame>Fasting, one time measurement after 8 hours</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">39</enrollment>
  <condition>Intestinal Diseases</condition>
  <condition>Irritable Bowel Syndrome</condition>
  <condition>Constipation</condition>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IBS-C</arm_group_label>
    <description>Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Permeability measurement</intervention_name>
    <description>Saccharide excretion was compared between IBS-C and healthy volunteers</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>IBS-C</arm_group_label>
    <other_name>12C Mannitol</other_name>
    <other_name>13C Mannitol</other_name>
    <other_name>Lactulose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Esophagogastroduodenoscopy</intervention_name>
    <description>Duodenal biopsies were collected from IBS-C and healthy volunteers</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>IBS-C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Flexible sigmoidoscopy</intervention_name>
    <description>Colonic biopsies were collected from IBS-C and healthy volunteers</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>IBS-C</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Colonic Biopsies Duodenal Biopsies Blood Urine Fecal&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        IBS-Constipation patients and healthy volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. 18 - 65 years old&#xD;
&#xD;
          2. IBS-C by Rome III criteria (for IBS-C participants)&#xD;
&#xD;
          3. No abdominal surgery (except appendectomy and cholecystectomy)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease&#xD;
&#xD;
          2. Use of tobacco products within the past 6 months&#xD;
&#xD;
          3. Use of NSAIDs or aspirin within the past week&#xD;
&#xD;
          4. Use of oral corticosteroids within the previous 6 weeks&#xD;
&#xD;
          5. Ingestion of artificial sweeteners such as Splenda (sucralose), Nutrasweet&#xD;
             (aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be&#xD;
             avoided are sugarless gums or mints and diet soda&#xD;
&#xD;
          6. Ingestion of any prescription, over the counter, or herbal medications which can&#xD;
             affect gastrointestinal transit 7 days before study begins&#xD;
&#xD;
               1. Any treatment specifically taken for IBS, including loperamide, cholestyramine,&#xD;
                  alosetron&#xD;
&#xD;
               2. Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors&#xD;
                  (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine);&#xD;
&#xD;
               3. All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in&#xD;
                  combination)&#xD;
&#xD;
               4. Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline).&#xD;
&#xD;
               5. Ultram&#xD;
&#xD;
               6. GI preparations&#xD;
&#xD;
                    -  Anti-nausea agents (e.g, trimethobenzamide, promethazine, prochlorperazine,&#xD;
                       dimenhydrinate, hydroxyzine)&#xD;
&#xD;
                    -  Osmotic laxative agents (e.g, lactulose, sorbitol or PEG solutions as&#xD;
                       Miralax and Glycolax)&#xD;
&#xD;
                    -  Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone);&#xD;
&#xD;
               7. Antimuscarinics;&#xD;
&#xD;
               8. Peppermint oil;&#xD;
&#xD;
               9. Systemic antibiotics, rifaximin, metronidazole.&#xD;
&#xD;
          7. Bleeding disorders or medications that increase risk of bleeding from mucosal&#xD;
             biopsies.&#xD;
&#xD;
          8. Score &gt; 8 for anxiety or depression on Hospital anxiety and depression scale.&#xD;
&#xD;
          9. Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Madhusudan Grover, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <results_first_submitted>July 31, 2017</results_first_submitted>
  <results_first_submitted_qc>August 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2019</results_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Madhusudan (Madhu) Grover, MBBS</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>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mannitol</mesh_term>
    <mesh_term>Lactulose</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Volunteers</title>
          <description>Healthy subjects ages 18 - 65 Must not have had any abdominal surgeries, IBS, IBD, microscopic colitis or celiac disease. Must not have used tobacco products in the last 6 months. Must not have used corticosteroids in the last 6 weeks. Must not have taken any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron . Must not be taking any drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors. Must not have taken anti-cholinergic agents (e.g. dicyclomine, hyoscyamine, propantheline), Ultram. No GI preparations&#xD;
Anti-nausea agents (e.g., trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine)&#xD;
Osmotic laxative agents (e.g, lactulose, sorbitol or PEG solutions as MiraLAX and GlycoLax) - Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone); Antimuscarinics;Peppermint oil;Systemic antibiotics, rifaximin, metronidazole. Must not have a bleeding disorder or medications that incr</description>
        </group>
        <group group_id="P2">
          <title>IBS-C</title>
          <description>Age (yr) 18 to 65 Must have IBS-C by Rome III criteria No abdominal surgery (except appendectomy and cholecystectomy) Exclusion criteria: Must have no History of IBD (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease. Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability) Use of oral corticosteroids within the previous 6 weeks No Ingestion of artificial sweeteners such as SplendaTM (sucralose), NutraSweet TM(aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins ny treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron No drugs with a known pharmacological activity at 5</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Volunteers</title>
          <description>Healthy volunteers between ages 18 - 65, who have not history of IBS.</description>
        </group>
        <group group_id="B2">
          <title>IBS-C</title>
          <description>Volunteers who have been diagnosed with IBS - Constipation (IBS-C)</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="18"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="37"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.37" spread="2.82"/>
                    <measurement group_id="B2" value="43.06" spread="2.78"/>
                    <measurement group_id="B3" value="44.24" spread="1.96"/>
                  </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="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.</title>
        <description>In vivo measurement of intestinal permeability using 13C mannitol &amp; lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.</description>
        <time_frame>8-24 hr post test-dose administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy&#xD;
Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers.&#xD;
Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy&#xD;
Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases.&#xD;
Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.</description>
          </group>
        </group_list>
        <measure>
          <title>Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.</title>
          <description>In vivo measurement of intestinal permeability using 13C mannitol &amp; lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.</description>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.004"/>
                    <measurement group_id="O2" value="0.02" spread="0.005"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.87</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.01</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lactose:C13 Mannitol Excretion Ratio 0-2hours</title>
        <time_frame>0-2 hr post-test dose administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy&#xD;
Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers.&#xD;
Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy&#xD;
Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases.&#xD;
Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.</description>
          </group>
        </group_list>
        <measure>
          <title>Lactose:C13 Mannitol Excretion Ratio 0-2hours</title>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.007" spread="0.0004"/>
                    <measurement group_id="O2" value="0.01" spread="0.001"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa</title>
        <time_frame>Baseline</time_frame>
        <population>Two participants ( 1 in Healthy volunteers and 1 in IBS-C ) were not analysed for the Baseline transmucosal resistance (TMR) of duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from duodenum from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from duodenum from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa</title>
          <population>Two participants ( 1 in Healthy volunteers and 1 in IBS-C ) were not analysed for the Baseline transmucosal resistance (TMR) of duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.</population>
          <units>Ω*sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.8" spread="1.94"/>
                    <measurement group_id="O2" value="28.16" spread="1.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa</title>
        <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
        <time_frame>3 hours post FITC-Dextran (4kDa) administration</time_frame>
        <population>Four participants (2 in Healthy volunteers and 2 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) concentration across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from each site from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from each site from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa</title>
          <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
          <population>Four participants (2 in Healthy volunteers and 2 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) concentration across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="123.3" spread="24.29"/>
                    <measurement group_id="O2" value="156.8" spread="33.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa</title>
        <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
        <time_frame>Over 3 hours post FITC-Dextran (4kDa) administration</time_frame>
        <population>Four participants ( 2 in Healthy volunteers and 2 in IBS-C ) were not analysed for the Rate of FITC-Dextran (4kDa) flux across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from each site from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from each site from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa</title>
          <description>This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.</description>
          <population>Four participants ( 2 in Healthy volunteers and 2 in IBS-C ) were not analysed for the Rate of FITC-Dextran (4kDa) flux across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.</population>
          <units>ng/hr/sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4980" spread="1044"/>
                    <measurement group_id="O2" value="6528" spread="1584"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Baseline Transmucosal Resistance (TMR) of Colonic Mucosa</title>
        <time_frame>Baseline</time_frame>
        <population>One participant in IBS-C was not analysed for the Baseline Transmucosal Resistance (TMR) of Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from colon from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from colon from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Baseline Transmucosal Resistance (TMR) of Colonic Mucosa</title>
          <population>One participant in IBS-C was not analysed for the Baseline Transmucosal Resistance (TMR) of Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen.</population>
          <units>Ω*sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.60" spread="1.70"/>
                    <measurement group_id="O2" value="19.06" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa</title>
        <time_frame>3 hours post FITC-Dextran (4kDa) administration</time_frame>
        <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from colon from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from colon from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa</title>
          <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="132.2" spread="24.23"/>
                    <measurement group_id="O2" value="122.5" spread="27.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa</title>
        <time_frame>Over 3 hours post FITC-Dextran (4kDa) administration</time_frame>
        <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from colon from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from colon from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured.Average TMR and Isc across 3-4 biopsies/subject were calculated.Paracellular flux across biopsies was measured using 4 kDa FITC-Dextran administered on the mucosal side (1 mg/mL chamber concentration). Cumulative flux at the end of three hours and rate of flux was calculated for FITC-Dextran</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa</title>
          <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>ng/hr/sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4931" spread="1156"/>
                    <measurement group_id="O2" value="6069" spread="1030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa</title>
        <time_frame>3 hours post E.coli Bio- Particle administration</time_frame>
        <population>11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from duodenum from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from duodenum from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa</title>
          <population>11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>CFU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.48*10^4" spread="2.6*10^3"/>
                    <measurement group_id="O2" value="1.82*10^4" spread="6.0*10^3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa</title>
        <time_frame>Over 3 hours post E.coli Bio- Particle administration</time_frame>
        <population>11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from duodenum from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from duodenum from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa</title>
          <population>11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>CFU/h/sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.42*10^5" spread="1.2*10^5"/>
                    <measurement group_id="O2" value="5.70*10^5" spread="1.90*10^5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa</title>
        <time_frame>3 hours post E.coli Bio- Particle administration</time_frame>
        <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Cumulative E.coli Bio- Particle K12 Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from colon from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from colon from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa</title>
          <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Cumulative E.coli Bio- Particle K12 Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>CFU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.07*10^4" spread="1.8*10^3"/>
                    <measurement group_id="O2" value="2.09*10^4" spread="6.8*10^3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa</title>
        <time_frame>Over 3 hours post E.coli Bio- Particle administration</time_frame>
        <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Four biopsies from colon from the Healthy Volunteers were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Four biopsies from colon from the IBS - C cases were mounted in 4 mL Ussing chambers (Physiologic Instruments, San Diego, CA, USA) exposing 0.031 sq.cm area, within 45 min of collection. Chambers were filled with Krebs with 10 mM mannitol (mucosal side) and Krebs with 10 mM glucose (submucosal side).Baseline transmucosal resistance (TMR) and short circuit current (Isc) of each tissue was measured. Average TMR and Isc across 3-4 biopsies/subject were calculated. Transcellular transport was studied by using translocation of the fluorescently labeled E. coli K-12 Bio-Particles was measured using a 107 CFU/mL chamber concentration on the mucosal side. Cumulative flux at the end of three hours and rate of flux was calculated for E. coli K-12 Bio-Particles.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa</title>
          <population>7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>CFU/h/sq.cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.26*10^5" spread="5.3*10^4"/>
                    <measurement group_id="O2" value="7.67*10^5" spread="4.19*10^5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duodenal Impedance</title>
        <time_frame>Baseline</time_frame>
        <population>12 participants (2 in Healthy volunteers and 10 in IBS-C) were not analysed for Duodenal impedance due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Volunteers fasted for eight hours and underwent sedated esophagogastroduodenoscopy. Duodenal impedance measurements were performed using a endoscopically passed catheter that measures electrical impedance of the duodenal epithelium by mucosal contact under direct visualization. A 2 mm diameter catheter was used with two 360° circumferential sensors placed at a separation of 2mm with the end of the distal ring being 1mm away from the catheter tip. The electrodes were connected to an impedance voltage transducer via thin wires, which ran the length of the catheter traversing through the working channel of the upper endoscope. The voltage generated by the transducer was limited to produce 10µA current at a frequency of 2 kHz. Impedance was measured every 90° in duodenal circumference with a decompressed lumen after suctioning of all fluid from the lumen. The catheter was embedded in the mucosa parallel to the two sensors and measurements were taken from a steady baseline for &gt;10s.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>IBS - C cases fasted for eight hours and underwent sedated esophagogastroduodenoscopy. Duodenal impedance measurements were performed using a endoscopically passed catheter that measures electrical impedance of the duodenal epithelium by mucosal contact under direct visualization. A 2 mm diameter catheter was used with two 360° circumferential sensors placed at a separation of 2mm with the end of the distal ring being 1mm away from the catheter tip. The electrodes were connected to an impedance voltage transducer via thin wires, which ran the length of the catheter traversing through the working channel of the upper endoscope. The voltage generated by the transducer was limited to produce 10µA current at a frequency of 2 kHz. Impedance was measured every 90° in duodenal circumference with a decompressed lumen after suctioning of all fluid from the lumen. The catheter was embedded in the mucosa parallel to the two sensors and measurements were taken from a steady baseline for &gt;10s.</description>
          </group>
        </group_list>
        <measure>
          <title>Duodenal Impedance</title>
          <population>12 participants (2 in Healthy volunteers and 10 in IBS-C) were not analysed for Duodenal impedance due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.</population>
          <units>Ω</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="705.9" spread="42.73"/>
                    <measurement group_id="O2" value="729.5" spread="64.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Serum Endotoxin (Bacterial LPS) Levels</title>
        <time_frame>Fasting, one time measurement after 8 hours</time_frame>
        <population>2 participants (1 in healthy volunteers and 1 in IBS-C) were not analysed for Mean Serum Endotoxin (Bacterial LPS) Levels due to various reasons such as non-availability of the blood sample, technical errors, etc.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Volunteers</title>
            <description>Fasting, EDTA anti-coagulated, whole blood was collected from Healthy Volunteers. Samples were analyzed using an EAA kit (Spectral Diagnostic Inc, Toronto, Ontario, Canada) that utilizes a monoclonal IgM antibody specific for gram-negative bacterial lipopolysaccharide (LPS). Samples were tested in duplicate within one hour of collection using a Berthold SmartLine luminometer (photon-counting). The endotoxin activity level was calculated as follows: chemiluminescence (test sample-negative control)/chemiluminescence (positive-negative control). Average values for each participant were expressed as absolute units.</description>
          </group>
          <group group_id="O2">
            <title>IBS - C</title>
            <description>Fasting, EDTA anti-coagulated, whole blood was collected from IBS - C cases. Samples were analyzed using an EAA kit (Spectral Diagnostic Inc, Toronto, Ontario, Canada) that utilizes a monoclonal IgM antibody specific for gram-negative bacterial lipopolysaccharide (LPS). Samples were tested in duplicate within one hour of collection using a Berthold SmartLine luminometer (photon-counting). The endotoxin activity level was calculated as follows: chemiluminescence (test sample-negative control)/chemiluminescence (positive-negative control). Average values for each participant were expressed as absolute units.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Serum Endotoxin (Bacterial LPS) Levels</title>
          <population>2 participants (1 in healthy volunteers and 1 in IBS-C) were not analysed for Mean Serum Endotoxin (Bacterial LPS) Levels due to various reasons such as non-availability of the blood sample, technical errors, etc.</population>
          <units>EU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.35" spread="0.02"/>
                    <measurement group_id="O2" value="0.36" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>15 months-from the first participant screening to the last participants completion date</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Healthy Volunteer</title>
          <description>Healthy volunteers between ages 18 - 65, who have no history of IBS.</description>
        </group>
        <group group_id="E2">
          <title>IBS-C</title>
          <description>ROME III IBS-C patients</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="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </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="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Indigestion/Heartburn</sub_title>
                <description>Indigestion/Heartburn</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Madhusudan Grover, MBBS</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-253-5384</phone>
      <email>Grover.Madhusudan@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/NCT02246647
org study id: 14-002382
nct id: NCT02246647
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Our overall objective with this study is firstly to provide a comprehensive assessment of
      intestinal permeability, mucosal barrier function using existing biomarkers and secondly to
      explore novel biomarkers for measuring intestinal permeability in patients with constipation
      predominant Irritable Bowel Syndrome (IBS-C).
In order to determine the differences in permeability in IBS-C in comparison with healthy
      volunteers, the following will be determined: differences in in vivo small intestinal and
      colonic permeability, differences in small intestinal and colonic mucosal barrier function,
      differences in effects of fecal supernatants on barrier function of T84 monolayers, and
      differences in novel biomarkers for intestinal permeability
observational model: Case-Control
time perspective: Cross-Sectional
measure: Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.
time frame: 8-24 hr post test-dose administration
description: In vivo measurement of intestinal permeability using 13C mannitol & lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.
measure: Lactose:C13 Mannitol Excretion Ratio 0-2hours
time frame: 0-2 hr post-test dose administration
measure: Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
time frame: Baseline
measure: Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
time frame: 3 hours post FITC-Dextran (4kDa) administration
description: This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
measure: Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa
time frame: Over 3 hours post FITC-Dextran (4kDa) administration
description: This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
measure: Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
time frame: Baseline
measure: Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
time frame: 3 hours post FITC-Dextran (4kDa) administration
measure: Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
time frame: Over 3 hours post FITC-Dextran (4kDa) administration
measure: Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
time frame: 3 hours post E.coli Bio- Particle administration
measure: Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
time frame: Over 3 hours post E.coli Bio- Particle administration
measure: Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
time frame: 3 hours post E.coli Bio- Particle administration
measure: Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
time frame: Over 3 hours post E.coli Bio- Particle administration
measure: Duodenal Impedance
time frame: Baseline
measure: Mean Serum Endotoxin (Bacterial LPS) Levels
time frame: Fasting, one time measurement after 8 hours
arm group label: Healthy volunteers
description: Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
arm group label: IBS-C
description: Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
intervention type: Diagnostic Test
intervention name: Permeability measurement
description: Saccharide excretion was compared between IBS-C and healthy volunteers
arm group label: Healthy volunteers
arm group label: IBS-C
other name: 12C Mannitol
other name: 13C Mannitol
other name: Lactulose
intervention type: Procedure
intervention name: Esophagogastroduodenoscopy
description: Duodenal biopsies were collected from IBS-C and healthy volunteers
arm group label: Healthy volunteers
arm group label: IBS-C
intervention type: Procedure
intervention name: Flexible sigmoidoscopy
description: Colonic biopsies were collected from IBS-C and healthy volunteers
arm group label: Healthy volunteers
arm group label: IBS-C
Colonic Biopsies Duodenal Biopsies Blood Urine Fecal
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Madhusudan Grover, MBBS
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Madhusudan (Madhu) Grover, MBBS
investigator title: Principal Investigator
mesh term: Irritable Bowel Syndrome
mesh term: Intestinal Diseases
mesh term: Constipation
mesh term: Mannitol
mesh term: Lactulose
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 