<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/NCT03242434</url>
  </required_header>
  <id_info>
    <org_study_id>206243</org_study_id>
    <nct_id>NCT03242434</nct_id>
  </id_info>
  <brief_title>Investigation of Thermal Injury on Intestinal Permeability in Both Thermal Injury and Healthy Participants</brief_title>
  <official_title>A Prospective, Longitudinal Study to Investigate the Effect of Thermal Injury on Intestinal Permeability and Systemic Inflammation (HESTIA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This longitudinal, prospective study aims to establish the magnitude and time course of&#xD;
      changes in intestinal permeability; establish the optimal method for assessment of intestinal&#xD;
      permeability in thermally injured participants: describe the participant population most&#xD;
      likely to benefit from a new medicinal product which could prevent changes in intestinal&#xD;
      permeability; and improve our understanding of the links between intestinal damage, changes&#xD;
      in the gut microbiome and microbial translocation to the systemic circulation following&#xD;
      thermal injury. The key factors of interest in this study are to understand the impact of&#xD;
      thermal injury on intestinal permeability in thermally injured participants compared to&#xD;
      healthy participants; and to understand the changes in intestinal permeability over time.&#xD;
      Approximately 15 eligible healthy participants and 25 thermally injury participants will be&#xD;
      included. The sugar test material (STM) comprises of Lactulose, Mannitol and Sucralose and&#xD;
      will be intermittently administered enterally to all the participants. The full duration of&#xD;
      the study for healthy participants will be approximately two weeks and 6 months for thermally&#xD;
      injured participants. In order to enter this study thermally injured participants will be&#xD;
      required to co-enroll in this study and an allied study entitled: A Multi-center, Prospective&#xD;
      Study to Examine the Relationship between Neutrophil Function and Sepsis in Adults and&#xD;
      Children with Severe Thermal Injury (SIFTI-2). (reference number IRAS ID: 200366).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This trial was supporting the development of an asset which was terminated, thus the data from&#xD;
    the study were no longer required.&#xD;
  </why_stopped>
  <start_date type="Actual">January 29, 2018</start_date>
  <completion_date type="Actual">March 26, 2018</completion_date>
  <primary_completion_date type="Actual">March 26, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1</measure>
    <time_frame>0 to 5 hours and 0 to 24 hours on Day 1</time_frame>
    <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. The impact of injury in thermal injury participants was compared with healthy participants using L/M ratio in urine.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants</measure>
    <time_frame>0 to 5 hours and 0 to 24 hours on Day 8 and Day 15</time_frame>
    <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants</measure>
    <time_frame>0 to 5 hours on Days 3, 5, 7, 11, 13 and 0 to 24 hours on Days 3, 5, 7, 9, 11 and 13</time_frame>
    <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Burns</condition>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Approximately 15 healthy participants of age 18 years or above will be included in the study and will receive STM intermittently via oral route. The total duration of study for healthy participants will be approximately 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thermal injury participants</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Approximately 25 thermally injured participants having TBSA more than or equal to 15 percent and who are co-consented to the SIFTI-2 and HESTIA studies will be included in the study and will receive STM intermittently via oral route. The total duration of study for thermal injury participants will be approximately 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lactulose and Mannitol solution</intervention_name>
    <description>Participants will receive 100 milliliter (mL) oral solution of Lactulose [5 grams (g)]/ Mannitol (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.</description>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Thermal injury participants</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sucralose</intervention_name>
    <description>Participants will receive 3 capsules of Sucralose (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.</description>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Thermal injury participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For Healthy participants:&#xD;
&#xD;
          -  Males or females must be greater than or equal to 18 years of age at the time of&#xD;
             signing informed consent.&#xD;
&#xD;
          -  Participants who are healthy as determined by the investigator following medical&#xD;
             evaluation including medical history, physical examination, and laboratory tests.&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant (negative&#xD;
             pregnancy testing at screening or Day 1 as needed) and not breastfeeding.&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
        For Thermally injured participants:&#xD;
&#xD;
          -  Participants must be greater than or equal to 18 years of age.&#xD;
&#xD;
          -  Participants who have sustained a burn (thermal injury) with a Total Burn Surface Area&#xD;
             (TBSA) greater than or equal to 15 percent.&#xD;
&#xD;
          -  Admission to the burn center (study site) less than or equal to 24 hours following&#xD;
             injury.&#xD;
&#xD;
          -  Able to take enteral fluids either orally or via a nasogastric tube (depends on facial&#xD;
             burn damage).&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant (negative&#xD;
             pregnancy testing at study entry) and not breastfeeding.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        For Healthy participants:&#xD;
&#xD;
          -  Healthy participants are excluded from this study if they are receiving&#xD;
             anti-coagulation therapy.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  A body mass index greater than 34 kilogram per meter square (kg/m^2).&#xD;
&#xD;
          -  An active history of alcohol dependency.&#xD;
&#xD;
          -  History of sensitivity to any of the STM, or components thereof or a history of drug&#xD;
             or other allergy that, in the opinion of the Investigator and/or GlaxoSmithKline (GSK)&#xD;
             Medical Monitor, contraindicates their participation.&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody and&#xD;
             confirmatory Hepatitis C Polymerase Chain Reaction (PCR) result within 3 months of&#xD;
             screening.&#xD;
&#xD;
          -  A positive pre-study urine drug/alcohol screen.&#xD;
&#xD;
          -  A positive test for Human Immuno-deficiency Virus (HIV) antibody.&#xD;
&#xD;
          -  Participants unable to swallow large capsules (the capsules will be shown to&#xD;
             participants at screening).&#xD;
&#xD;
          -  Galactosaemia or severe lactose intolerance.&#xD;
&#xD;
          -  Use of an antibiotic 2 weeks prior to study start (administration of the STM).&#xD;
&#xD;
          -  Gastroenteritis in the 2 weeks prior to study start (administration of the STM).&#xD;
&#xD;
        For thermally injured participants:&#xD;
&#xD;
          -  Chemical or electrical burn.&#xD;
&#xD;
          -  Multiple traumatic injuries with an Injury Severity Score (ISS) more than or equal to&#xD;
             16.&#xD;
&#xD;
          -  Participants received substantial undocumented management prior to arrival at the&#xD;
             study site (burn center) e.g. from paramedics or in a local accident and emergency&#xD;
             department.&#xD;
&#xD;
          -  Systemic corticoidsteroid use.&#xD;
&#xD;
          -  Intravenous (IV) Mannitol use.&#xD;
&#xD;
          -  HIV infection.&#xD;
&#xD;
          -  Viral Hepatitis B or C infection.&#xD;
&#xD;
          -  Gastrointestinal disease (e.g. inflammatory bowel disease) which may affect intestinal&#xD;
             permeability.&#xD;
&#xD;
          -  Previous bowel resection (e.g. hemicolectomy, small bowel resection).&#xD;
&#xD;
          -  Galactosaemia or severe lactose intolerance.&#xD;
&#xD;
          -  Bowel obstruction.&#xD;
&#xD;
          -  Renal dysfunction requiring renal replacement therapy (end-stage renal failure prior&#xD;
             to thermal injury).&#xD;
&#xD;
          -  Active autoimmune disease and receiving immunomodulatory therapy e.g. rheumatoid&#xD;
             arthritis anti-Tumor Necrosis Factor (TNF).&#xD;
&#xD;
          -  Active chemotherapy for cancers or immunoremittive therapies (prednisolone,&#xD;
             Adalimumab) within 60 days of thermal injury.&#xD;
&#xD;
          -  Premorbid conditions of malignancy currently under treatment.&#xD;
&#xD;
          -  Previous bilateral lower extremity amputation.&#xD;
&#xD;
          -  Decision not to treat the participant due to futility.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <results_first_submitted>March 25, 2019</results_first_submitted>
  <results_first_submitted_qc>July 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 19, 2019</results_first_posted>
  <last_update_submitted>July 11, 2019</last_update_submitted>
  <last_update_submitted_qc>July 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mannitol</keyword>
  <keyword>Intestinal permeability</keyword>
  <keyword>Thermal injury</keyword>
  <keyword>HESTIA</keyword>
  <keyword>Sucralose</keyword>
  <keyword>Lactulose</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03242434/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03242434/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was a longitudinal study which involved healthy participants and participants who had sustained a thermal injury. The study was conducted in United Kingdom. This study was terminated early prior to the full sample size being achieved as the development of the formulation was terminated.</recruitment_details>
      <pre_assignment_details>A total 23 participants were screened for study of which 5 participants were screen failure and 18 participants were enrolled in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Healthy Participants</title>
          <description>Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram [g]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.</description>
        </group>
        <group group_id="P2">
          <title>Thermal Injury Participants</title>
          <description>Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>One participant from healthy participants was excluded due to protocol deviation.</population>
      <group_list>
        <group group_id="B1">
          <title>Healthy Participants</title>
          <description>Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram [g]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.</description>
        </group>
        <group group_id="B2">
          <title>Thermally Injured Participants</title>
          <description>Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.</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="14"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Evaluable Population.</description>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.4" spread="9.43"/>
                    <measurement group_id="B2" value="52.0" spread="21.00"/>
                    <measurement group_id="B3" value="43.3" spread="12.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Evaluable Population</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Evaluable Population</description>
          <units>Count of Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Central/South Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1</title>
        <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. The impact of injury in thermal injury participants was compared with healthy participants using L/M ratio in urine.</description>
        <time_frame>0 to 5 hours and 0 to 24 hours on Day 1</time_frame>
        <population>Evaluable Population included of all participants in the safety population excluding any healthy volunteers that received any concomitant medication or food and drink containing Sugar Test Material (STM) as identified by review of the protocol deviation. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Participants</title>
            <description>Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram [g]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.</description>
          </group>
          <group group_id="O2">
            <title>Thermally Injured Participants</title>
            <description>Participants were invited undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1</title>
          <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. The impact of injury in thermal injury participants was compared with healthy participants using L/M ratio in urine.</description>
          <population>Evaluable Population included of all participants in the safety population excluding any healthy volunteers that received any concomitant medication or food and drink containing Sugar Test Material (STM) as identified by review of the protocol deviation. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, 0 to 5 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0078" spread="0.00102"/>
                    <measurement group_id="O2" value="0.0415" spread="0.06243"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1, 0 to 24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0093" spread="0.00409"/>
                    <measurement group_id="O2" value="0.0296" spread="0.04031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants</title>
        <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
        <time_frame>0 to 5 hours and 0 to 24 hours on Day 8 and Day 15</time_frame>
        <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Participants</title>
            <description>Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram [g]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants</title>
          <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
          <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 8 (0-5 hours)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0132" spread="0.020600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 (0-5 hours)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0016" spread="0.00548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 (0-24 hours)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0092" spread="0.01304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 (0-24 hours)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0090" spread="0.00698"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants</title>
        <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
        <time_frame>0 to 5 hours on Days 3, 5, 7, 11, 13 and 0 to 24 hours on Days 3, 5, 7, 9, 11 and 13</time_frame>
        <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Thermally Injured Participants</title>
            <description>Participants were invited undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants</title>
          <description>Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.</description>
          <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3, (0-5 hours), n= 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0037" spread="0.09936"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5, (0-5 hours), n= 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0213" spread="0.08213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7, (0-5 hours), n= 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0566" spread="0.07509"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11, (0-5 hours), n= 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1044" spread="NA">NA indicates data was not available as standard deviation could not be calculated for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 13, (0-5 hours), n= 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0043" spread="NA">NA indicates data was not available as standard deviation could not be calculated for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3, (0-24 hours), n= 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0111" spread="0.09085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5, (0-24 hours), n= 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0046" spread="0.06456"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7, (0-24 hours), n= 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0178" spread="0.02640"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 9, (0-24 hours), n= 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0327" spread="0.05953"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11, (0-24 hours), n= 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0218" spread="0.05846"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 13, (0-24 hours), n= 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0634" spread="NA">NA indicates data was not available as standard deviation could not be calculated for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious adverse events (SAE) and Non-SAE were collected from Day 1 up to 6 months for thermal injury participants and SAE and Non-SAE were collected from Day 1 up to Day 15 for healthy participants. Safety Population comprised of all participants who received at least one dose of STM and have at least one post-dose safety assessment.</time_frame>
      <desc>Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.</desc>
      <group_list>
        <group group_id="E1">
          <title>Healthy Participants</title>
          <description>Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram [g]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.</description>
        </group>
        <group group_id="E2">
          <title>Thermally Injured Participants</title>
          <description>Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.1</default_vocab>
        <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="5" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Reponse Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.com</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/NCT03242434
org study id: 206243
nct id: NCT03242434
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This longitudinal, prospective study aims to establish the magnitude and time course of
      changes in intestinal permeability; establish the optimal method for assessment of intestinal
      permeability in thermally injured participants: describe the participant population most
      likely to benefit from a new medicinal product which could prevent changes in intestinal
      permeability; and improve our understanding of the links between intestinal damage, changes
      in the gut microbiome and microbial translocation to the systemic circulation following
      thermal injury. The key factors of interest in this study are to understand the impact of
      thermal injury on intestinal permeability in thermally injured participants compared to
      healthy participants; and to understand the changes in intestinal permeability over time.
      Approximately 15 eligible healthy participants and 25 thermally injury participants will be
      included. The sugar test material (STM) comprises of Lactulose, Mannitol and Sucralose and
      will be intermittently administered enterally to all the participants. The full duration of
      the study for healthy participants will be approximately two weeks and 6 months for thermally
      injured participants. In order to enter this study thermally injured participants will be
      required to co-enroll in this study and an allied study entitled: A Multi-center, Prospective
      Study to Examine the Relationship between Neutrophil Function and Sepsis in Adults and
      Children with Severe Thermal Injury (SIFTI-2). (reference number IRAS ID: 200366).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1
time frame: 0 to 5 hours and 0 to 24 hours on Day 1
description: Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. The impact of injury in thermal injury participants was compared with healthy participants using L/M ratio in urine.
measure: Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
time frame: 0 to 5 hours and 0 to 24 hours on Day 8 and Day 15
description: Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.
measure: Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
time frame: 0 to 5 hours on Days 3, 5, 7, 11, 13 and 0 to 24 hours on Days 3, 5, 7, 9, 11 and 13
description: Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.
arm group label: Healthy controls
arm group type: Other
description: Approximately 15 healthy participants of age 18 years or above will be included in the study and will receive STM intermittently via oral route. The total duration of study for healthy participants will be approximately 2 weeks.
arm group label: Thermal injury participants
arm group type: Other
description: Approximately 25 thermally injured participants having TBSA more than or equal to 15 percent and who are co-consented to the SIFTI-2 and HESTIA studies will be included in the study and will receive STM intermittently via oral route. The total duration of study for thermal injury participants will be approximately 6 months.
intervention type: Other
intervention name: Lactulose and Mannitol solution
description: Participants will receive 100 milliliter (mL) oral solution of Lactulose [5 grams (g)]/ Mannitol (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.
arm group label: Healthy controls
arm group label: Thermal injury participants
intervention type: Other
intervention name: Sucralose
description: Participants will receive 3 capsules of Sucralose (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.
arm group label: Healthy controls
arm group label: Thermal injury participants
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Burns
mesh term: Mannitol
mesh term: Lactulose
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 