<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/NCT01683331</url>
  </required_header>
  <id_info>
    <org_study_id>1R01DK092475-01</org_study_id>
    <nct_id>NCT01683331</nct_id>
  </id_info>
  <brief_title>A Clinical Trial to Prevent New Onset Diabetes After Transplantation</brief_title>
  <acronym>ITP-NODAT</acronym>
  <official_title>A Clinical Trial to Prevent New Onset Diabetes After Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      Specific Aim 1: To determine the clinical efficacy of early initiation of insulin therapy in&#xD;
      decreasing the incidence of NODAT among de novo kidney transplant patients with manifested&#xD;
      post-transplant hyperglycemia during the first week after transplantation.&#xD;
&#xD;
      Hypothesis 1: Early initiation of insulin therapy protects beta-cell from early stress&#xD;
      related to the surgery and use of higher doses of immunosuppressive medications, and leads to&#xD;
      lower incidence of NODAT at 1 and 2 years.&#xD;
&#xD;
      Specific Aim 2: To determine the improvement in overall glycemic control with the early&#xD;
      initiation of insulin therapy.&#xD;
&#xD;
      Hypothesis 2: Early initiation of insulin therapy results in greater overall control of&#xD;
      glycemia compared to standard care of dietary counseling, life-style modification, oral&#xD;
      hypoglycemic agents and/or insulin as needed at 1 year.&#xD;
&#xD;
      Specific Aim 3: To determine the improvement in beta-cell function among patients assigned to&#xD;
      the early initiation of insulin therapy at one year post-transplantation.&#xD;
&#xD;
      Hypothesis 3: Early initiation of insulin therapy protects beta-cell from glucotoxicity of&#xD;
      post-transplant hyperglycemia and preserves better beta-cell function at 1 year.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2012</start_date>
  <completion_date type="Actual">February 27, 2018</completion_date>
  <primary_completion_date type="Actual">February 27, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation</measure>
    <time_frame>12 months</time_frame>
    <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation</measure>
    <time_frame>24 months</time_frame>
    <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours OGTT values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy;</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of Impaired Fasting Glycemia and Impaired Glucose Tolerance 6, 12 and 24 Months After Transplantation.</measure>
    <time_frame>6, 12 and 24 months</time_frame>
    <description>Following American Diabetes Association's definition:&#xD;
Impaired fasting glycemia: fasting glucose levels between 100 and 125 mg/dl;&#xD;
Impaired glucose tolerance: 2 hours' OGTT values between 140 and 199 mg/dl;</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">251</enrollment>
  <condition>Prevention of New Onset Diabetes Among Kidney Transplant Patients</condition>
  <arm_group>
    <arm_group_label>Insulin treatment for hyperglycemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neutral Protamine Hagedorn (NPH) Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin treatment for hyperglycemia</intervention_name>
    <arm_group_label>Insulin treatment for hyperglycemia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients (&gt; 18 years) with end stage renal disease (ESRD) undergoing kidney&#xD;
             transplantation;&#xD;
&#xD;
          2. Standard triple immunosuppressive medications following kidney transplantation&#xD;
             including tacrolimus, mycophenolate mofetil and corticosteroids;&#xD;
&#xD;
          3. Capable to understand the study protocol and to give informed consent;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Type 1 and 2 Diabetes Mellitus (DM) either as co-morbidity or cause of ESRD;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Akinlolu Ojo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <results_first_submitted>February 26, 2019</results_first_submitted>
  <results_first_submitted_qc>February 26, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 20, 2019</results_first_posted>
  <last_update_submitted>February 26, 2019</last_update_submitted>
  <last_update_submitted_qc>February 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Akinlolu Ojo</investigator_full_name>
    <investigator_title>Emeritus Professor of Medicine, Active</investigator_title>
  </responsible_party>
  <keyword>Kidney transplant</keyword>
  <keyword>New onset diabetes</keyword>
  <keyword>Prevention</keyword>
  <keyword>Insulin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT01683331/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of 42 participants randomized prior to kidney transplantation at University of Michigan, 6 did not undergo study procedure due to medical conditions that developed in the immediate postoperative period which prevented them from going forward in the study. Data are not available on the 209 participants randomized through the University of Austria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Insulin Treatment for Hyperglycemia</title>
          <description>NPH Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care</title>
          <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Began Dosage</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>12 Months</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>24 Months</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Insulin Treatment for Hyperglycemia</title>
          <description>NPH Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care</title>
          <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</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="18"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="52.6" spread="13.9"/>
                    <measurement group_id="B2" value="44.6" spread="15.5"/>
                    <measurement group_id="B3" value="48.6" spread="15.1"/>
                  </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="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="29"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation</title>
        <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Insulin Treatment for Hyperglycemia</title>
            <description>NPH Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</description>
          </group>
        </group_list>
        <measure>
          <title>The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation</title>
          <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="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="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.87</p_value>
            <method>Chi-squared</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.01</ci_lower_limit>
            <ci_upper_limit>1.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation</title>
        <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours OGTT values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy;</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Insulin Treatment for Hyperglycemia</title>
            <description>NPH Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</description>
          </group>
        </group_list>
        <measure>
          <title>The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation</title>
          <description>NODAT will be defined according to American Diabetes Association definition:&#xD;
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or&#xD;
2 hours OGTT values equal or greater than 200 mg/dl; and/or&#xD;
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or&#xD;
On oral hypoglycemic agents and/or insulin therapy;</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="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="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.92</p_value>
            <method>Chi-squared</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.2</ci_lower_limit>
            <ci_upper_limit>2.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Incidence of Impaired Fasting Glycemia and Impaired Glucose Tolerance 6, 12 and 24 Months After Transplantation.</title>
        <description>Following American Diabetes Association's definition:&#xD;
Impaired fasting glycemia: fasting glucose levels between 100 and 125 mg/dl;&#xD;
Impaired glucose tolerance: 2 hours' OGTT values between 140 and 199 mg/dl;</description>
        <time_frame>6, 12 and 24 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Insulin Treatment for Hyperglycemia</title>
          <description>NPH Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG &gt; 240, NPH initiation: 14, dose increases by 4; For pts. with CPG &gt; 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG &gt; 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG &gt; 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-&lt;100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-&lt;80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG &lt;60 mg/dl, NPH initiation: 0, ½ of previous dose.</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care</title>
          <description>Patients assigned in this arm will receive standard of care following their kidney transplantation.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="18"/>
              </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="15" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Low Vitamin D</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="18"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The original trial design was to include 250 participants. Data from the Austrian site has not been provided to the PI, thus limiting the analysis to a much smaller population.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Akinlolu Ojo</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734 936-4890</phone>
      <email>aojo@umich.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/NCT01683331
org study id: 1R01DK092475-01
nct id: NCT01683331
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
Specific Aim 1: To determine the clinical efficacy of early initiation of insulin therapy in
      decreasing the incidence of NODAT among de novo kidney transplant patients with manifested
      post-transplant hyperglycemia during the first week after transplantation.

      Hypothesis 1: Early initiation of insulin therapy protects beta-cell from early stress
      related to the surgery and use of higher doses of immunosuppressive medications, and leads to
      lower incidence of NODAT at 1 and 2 years.

      Specific Aim 2: To determine the improvement in overall glycemic control with the early
      initiation of insulin therapy.

      Hypothesis 2: Early initiation of insulin therapy results in greater overall control of
      glycemia compared to standard care of dietary counseling, life-style modification, oral
      hypoglycemic agents and/or insulin as needed at 1 year.

      Specific Aim 3: To determine the improvement in beta-cell function among patients assigned to
      the early initiation of insulin therapy at one year post-transplantation.

      Hypothesis 3: Early initiation of insulin therapy protects beta-cell from glucotoxicity of
      post-transplant hyperglycemia and preserves better beta-cell function at 1 year.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation
time frame: 12 months
description: NODAT will be defined according to American Diabetes Association definition:
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or
2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or
On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.
measure: The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation
time frame: 24 months
description: NODAT will be defined according to American Diabetes Association definition:
Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or
2 hours OGTT values equal or greater than 200 mg/dl; and/or
Glycosylated hemoglobin A1c equal or greater than 6.5; and/or
On oral hypoglycemic agents and/or insulin therapy;
measure: Incidence of Impaired Fasting Glycemia and Impaired Glucose Tolerance 6, 12 and 24 Months After Transplantation.
time frame: 6, 12 and 24 months
description: Following American Diabetes Association's definition:
Impaired fasting glycemia: fasting glucose levels between 100 and 125 mg/dl;
Impaired glucose tolerance: 2 hours' OGTT values between 140 and 199 mg/dl;
arm group label: Insulin treatment for hyperglycemia
arm group type: Active Comparator
description: Neutral Protamine Hagedorn (NPH) Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG > 240, NPH initiation: 14, dose increases by 4; For pts. with CPG > 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG > 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG > 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-<100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-<80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG <60 mg/dl, NPH initiation: 0, ½ of previous dose.
arm group label: Standard of care
arm group type: No Intervention
description: Patients assigned in this arm will receive standard of care following their kidney transplantation.
intervention type: Drug
intervention name: Insulin treatment for hyperglycemia
arm group label: Insulin treatment for hyperglycemia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Akinlolu Ojo, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Akinlolu Ojo
investigator title: Emeritus Professor of Medicine, Active
mesh term: Diabetes Mellitus
mesh term: Insulin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The original trial design was to include 250 participants. Data from the Austrian site has not been provided to the PI, thus limiting the analysis to a much smaller population.
point of contact: 