<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/NCT01666665</url>
  </required_header>
  <id_info>
    <org_study_id>12-142</org_study_id>
    <nct_id>NCT01666665</nct_id>
  </id_info>
  <brief_title>Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin</brief_title>
  <official_title>Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Medical Branch, Galveston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shriners Hospitals for Children</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Medical Branch, Galveston</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Massive pediatric burns are associated with a persistent and sustained hypermetabolic&#xD;
      response characterized by elevated levels of circulating catecholamine's, cortisol, and&#xD;
      glucagon's, which can cause extreme muscle wasting, immunodeficiency, and delay in wound&#xD;
      healing. Insulin and metformin have demonstrated anabolic activity with minimal associated&#xD;
      side effects. However, it is unknown whether the beneficial effects arise from tight&#xD;
      euglycemic control or direct effect of insulin action. We hypothesize that during acute&#xD;
      hospitalization, administration of metformin at a dose titrated to maintain blood glucose&#xD;
      between 80-180 mg/dl will accelerate wound healing and recovery in children with severe&#xD;
      thermal injury and will have beneficial long-term effects on muscle strength, immune&#xD;
      function, and wound healing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Metformin treated patients will be compared to control patients. Both groups will receive&#xD;
      insulin therapy for blood glucose &gt;180mg/dl. Insulin will be titrated according to hospital&#xD;
      sliding scale.&#xD;
&#xD;
      The use of insulin or metformin will benefit burned children by improving muscle protein&#xD;
      build-up, speeding wound healing and reversing growth arrest, improving the immune response,&#xD;
      and positively affecting long-term rehabilitation.&#xD;
&#xD;
      The results of this study may initiate a change in standard of care as it is found that&#xD;
      simply the reduction of blood glucose by metformin, improves patient outcomes as metformin&#xD;
      can be administered without the added complication of hypoglycemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    At the request of the study site, this study has been closed and access to study-related data&#xD;
    is unavailable. We are unable to submit the results-data.&#xD;
  </why_stopped>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">April 23, 2019</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin resistance</measure>
    <time_frame>Measure changes between admission and 2 years post burn</time_frame>
    <description>As measured by OGTT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Protein synthesis</measure>
    <time_frame>Measure changes between admission and 1 years post burn</time_frame>
    <description>As measured by stable isotope infusion study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morbidity</measure>
    <time_frame>Measure changes between admission and 2 years post burn</time_frame>
    <description>As measured by Organ Failure assessments</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Hypermetabolism</condition>
  <condition>Hyperglycemia</condition>
  <arm_group>
    <arm_group_label>metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>sugar pill up to 3 times per day for 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months</description>
    <arm_group_label>metformin</arm_group_label>
    <other_name>glucophage</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugar pill</intervention_name>
    <description>Sugar pill up to 3 times per day for 12 months</description>
    <arm_group_label>Sugar pill</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient age 10-19&#xD;
&#xD;
          -  Primary diagnosis of ≥ 20 Total Burn Surface Area Burn (TBSAB )&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Decision not to treat due to burn injury severity&#xD;
&#xD;
          -  Known history of AIDS, ARC, HIV&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Previous diagnosis (pre -burn) of renal failure, liver disease or hepatic dysfunction-&#xD;
             Serum Creatinine &gt;1.5mg/dL for males and &gt;1.4mg/dL for females, after fluid&#xD;
             resuscitation (Clinical definition of kidney damage)&#xD;
&#xD;
          -  Pre-existing type 1 diabetes mellitus&#xD;
&#xD;
          -  Pre Existing type 2 diabetes mellitus and receiving treatment&#xD;
&#xD;
          -  Allergies to Metformin&#xD;
&#xD;
          -  Acute or chronic acidosis (lactic or any other metabolic type) and renal failure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>19 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David N Herndon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shriners Hospitals for Children</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77551</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 6, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>November 26, 2019</last_update_submitted>
  <last_update_submitted_qc>November 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Burn</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Hyperglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 15, 2023</submitted>
    <returned>July 3, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01666665
org study id: 12-142
nct id: NCT01666665
lead sponsor: 
collaborator: 
has dmc: Yes
Massive pediatric burns are associated with a persistent and sustained hypermetabolic
      response characterized by elevated levels of circulating catecholamine's, cortisol, and
      glucagon's, which can cause extreme muscle wasting, immunodeficiency, and delay in wound
      healing. Insulin and metformin have demonstrated anabolic activity with minimal associated
      side effects. However, it is unknown whether the beneficial effects arise from tight
      euglycemic control or direct effect of insulin action. We hypothesize that during acute
      hospitalization, administration of metformin at a dose titrated to maintain blood glucose
      between 80-180 mg/dl will accelerate wound healing and recovery in children with severe
      thermal injury and will have beneficial long-term effects on muscle strength, immune
      function, and wound healing.
Metformin treated patients will be compared to control patients. Both groups will receive
      insulin therapy for blood glucose >180mg/dl. Insulin will be titrated according to hospital
      sliding scale.

      The use of insulin or metformin will benefit burned children by improving muscle protein
      build-up, speeding wound healing and reversing growth arrest, improving the immune response,
      and positively affecting long-term rehabilitation.

      The results of this study may initiate a change in standard of care as it is found that
      simply the reduction of blood glucose by metformin, improves patient outcomes as metformin
      can be administered without the added complication of hypoglycemia.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Insulin resistance
time frame: Measure changes between admission and 2 years post burn
description: As measured by OGTT
measure: Protein synthesis
time frame: Measure changes between admission and 1 years post burn
description: As measured by stable isotope infusion study
measure: Morbidity
time frame: Measure changes between admission and 2 years post burn
description: As measured by Organ Failure assessments
arm group label: metformin
arm group type: Active Comparator
description: Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months
arm group label: Sugar pill
arm group type: Placebo Comparator
description: sugar pill up to 3 times per day for 12 months
intervention type: Drug
intervention name: Metformin
description: Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months
arm group label: metformin
other name: glucophage
intervention type: Drug
intervention name: Sugar pill
description: Sugar pill up to 3 times per day for 12 months
arm group label: Sugar pill
other name: placebo
criteria: 
gender: All
minimum age: 10 Years
maximum age: 19 Years
healthy volunteers: No
last name: David N Herndon, MD
role: Principal Investigator
affiliation: University of Texas
facility: 
country: United States
responsible party type: Sponsor
mesh term: Insulin Resistance
mesh term: Hyperglycemia
mesh term: Metformin
sharing ipd: No
submitted: June 15, 2023
returned: July 3, 2023