<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/NCT02251431</url>
  </required_header>
  <id_info>
    <org_study_id>014-149</org_study_id>
    <secondary_id>D5551L00004/ISSEXEN0013</secondary_id>
    <nct_id>NCT02251431</nct_id>
  </id_info>
  <brief_title>Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome</brief_title>
  <official_title>MB001-067 A PROSPECTIVE, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, RANDOMIZED TRIAL OF EXTENDED RELEASE EXENATIDE VERSUS PLACEBO (COHORT A) AND A PROSPECTIVE, SINGLE GROUP, OPEN-LABEL, BLINDED OUTCOME TRIAL OF EXTENDED RELEASE EXENATIDE (COHORT B) IN DIABETIC PATIENTS WITH TYPE 4 CARDIORENAL SYNDROME (EXTEND-CRS TRIAL) AMENDMENT 3</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylor Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Among adult individuals with type 2 diabetes mellitus and at risk for heart failure with&#xD;
      impaired relaxation of the heart mildly reduced kidney filtration function (Type 4&#xD;
      cardiorenal syndrome) this trial will evaluate the quantitative impact of 38 weeks of&#xD;
      treatment with exenatide extended-release injections versus placebo. on a cardiac biomarker&#xD;
      blood test score, cardiac fibrosis seen on magnetic resonance scanning, cardiac strain&#xD;
      identified by ultrasonography and strain rate imaging, and a kidney urine biomarker score.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Aim&#xD;
&#xD;
      Among adult individuals with type 2 diabetes mellitus (T2DM) and at risk for diastolic heart&#xD;
      failure (DHF) and mildly reduced renal filtration function (Type 4 cardiorenal syndrome), to&#xD;
      evaluate the quantitative impact on the MISS (myocardial injury summary score) cardiac&#xD;
      biomarker score, cardiac fibrosis by MRI, cardiac strain by ultrasonography and strain rate&#xD;
      imaging, and KISS (kidney injury summary score) kidney biomarker score after 38 weeks of&#xD;
      treatment with exenatide extended-release or placebo.&#xD;
&#xD;
      Secondary Aim&#xD;
&#xD;
      To evaluate the inter-relationships between demographic, clinical, and biochemical variables&#xD;
      (MISS score, KISS score) and of progressive cardiac fibrosis as assessed by MRI, strain-rate&#xD;
      imaging, and in adult individuals with T2DM and at risk for DHF (Type 4 cardiorenal&#xD;
      syndrome).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2015</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Galectin-3</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in plasma galectin-3 (pg/ml)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ST2</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in plasma ST2 (pg/ml)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>NGAL</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>KIM-1</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>L-FABP</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine L-type fatty acid binding protein:Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IL-18</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine interleukin-18:Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alpha GST</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Troponin I</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in plasma ultrasensitive troponin I (pg/ml)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pi GST</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in pi glutathione S-transferase (piGST):Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>NAG</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cystatin-C</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>BNP</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in plasma B-type natriuretic peptide BNP (pg/ml)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ACR</measure>
    <time_frame>38 weeks</time_frame>
    <description>Mean change in urine albumin:Cr ratio (ACR)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <condition>Chronic Kidney Disease</condition>
  <condition>Left Ventricular Diastolic Dysfunction</condition>
  <arm_group>
    <arm_group_label>Exenatide-extended release</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo subcutaneously once per week x 38 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BYDUREON</intervention_name>
    <description>Exenatide-extended release, Cohorts A and B</description>
    <arm_group_label>Exenatide-extended release</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Cohort A only</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Matching placebo subcutaneous injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Type 2 diabetes mellitus with hemoglobin A1C 6.6-9.9% with or without the use of&#xD;
             insulin&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) between 50 and 90 ml/min/1.73 m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy or intolerance to gadolinium&#xD;
&#xD;
          -  Implanted cardiac pacemaker, defibrillator, loop recorder, or other implanted metallic&#xD;
             device&#xD;
&#xD;
          -  Any other metallic implanted device that is a contra-indication to MRI scanning&#xD;
&#xD;
          -  eGFR &lt; 50 ml/min/1.73 m2&#xD;
&#xD;
          -  eGFR &gt; 90 ml/min/1.73 m2&#xD;
&#xD;
          -  Patient has ever been treated with an approved or investigational GLP-1 receptor&#xD;
             agonist e.g. BYETTA™ (exenatide), BYDUREON™ (Exenatide extended-release), VICTOZA™&#xD;
             (liraglutide), or taspoglutide&#xD;
&#xD;
          -  Patient is enrolled in another experimental protocol which involves the use of an&#xD;
             investigational drug or device, or an intervention that would interfere with the&#xD;
             conduct of the trial.&#xD;
&#xD;
          -  Disorders of iron metabolism&#xD;
&#xD;
          -  Collagen vascular diseases&#xD;
&#xD;
          -  Myocardial infarction&#xD;
&#xD;
          -  Use of DDP4 inhibitors, and PPAR gamma agonists&#xD;
&#xD;
          -  Pregnancy or planned pregnancy during the trial period&#xD;
&#xD;
          -  Hemoglobin A1C of ≥ 10.0% or &lt;6.6%&#xD;
&#xD;
          -  Fasting glucose ≥ 260 mg/dl&#xD;
&#xD;
          -  Clinically significant abnormal baseline laboratories&#xD;
&#xD;
          -  Morbid obesity or body girth that prohibits the ability to undergo echocardiography or&#xD;
             MRI scanning with high-quality image results&#xD;
&#xD;
          -  Renal transplantation&#xD;
&#xD;
          -  Severe gastrointestinal, liver, or neurodegenerative disease&#xD;
&#xD;
          -  Decompensated liver cirrhosis (Child-Pugh score &gt;7)&#xD;
&#xD;
          -  New York Heart Association Class III or IV heart failure&#xD;
&#xD;
          -  Patients have alanine aminotransaminase (ALT) greater than 5 times the upper limit of&#xD;
             the reference range.&#xD;
&#xD;
          -  Prior pancreatitis&#xD;
&#xD;
          -  Personal or family history of medullary thyroid adenoma or carcinoma (MTC)&#xD;
&#xD;
          -  Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).&#xD;
&#xD;
          -  History of severe hypoglycemia&#xD;
&#xD;
          -  Prior bariatric surgery&#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>Peter A McCullough, MD, MPH</last_name>
    <role>Study Chair</role>
    <affiliation>Baylor Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Chinnaiyan KM, Alexander D, Maddens M, McCullough PA. Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. Am Heart J. 2007 Feb;153(2):189-200. doi: 10.1016/j.ahj.2006.10.022.</citation>
    <PMID>17239676</PMID>
  </reference>
  <reference>
    <citation>Davidson MH. Cardiovascular effects of glucagonlike peptide-1 agonists. Am J Cardiol. 2011 Aug 2;108(3 Suppl):33B-41B. doi: 10.1016/j.amjcard.2011.03.046.</citation>
    <PMID>21802579</PMID>
  </reference>
  <reference>
    <citation>Levine GD, Rosai J, Bearman RM, Polliack A. The fine structure of thymoma, with emphasis on its differential diagnosis. A study of ten cases. Am J Pathol. 1975 Oct;81(1):49-86.</citation>
    <PMID>1080957</PMID>
  </reference>
  <reference>
    <citation>Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA. Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011 Jan;34(1):90-5. doi: 10.2337/dc10-1393. Epub 2010 Oct 7.</citation>
    <PMID>20929995</PMID>
  </reference>
  <reference>
    <citation>McCullough PA, Olobatoke A, Vanhecke TE. Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med. 2011;12(4):200-10. doi: 10.3909/ricm0624. Erratum In: Rev Cardiovasc Med. 2012;13(1):e52.</citation>
    <PMID>22249510</PMID>
  </reference>
  <reference>
    <citation>Wang YC, Yu CC, Chiu FC, Tsai CT, Lai LP, Hwang JJ, Lin JL. Soluble ST2 as a biomarker for detecting stable heart failure with a normal ejection fraction in hypertensive patients. J Card Fail. 2013 Mar;19(3):163-8. doi: 10.1016/j.cardfail.2013.01.010.</citation>
    <PMID>23482076</PMID>
  </reference>
  <reference>
    <citation>Jellis C, Martin J, Narula J, Marwick TH. Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol. 2010 Jul 6;56(2):89-97. doi: 10.1016/j.jacc.2010.02.047.</citation>
    <PMID>20620723</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>March 21, 2023</results_first_submitted>
  <results_first_submitted_qc>April 24, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 17, 2023</results_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diabetes mellitus</keyword>
  <keyword>chronic kidney disease</keyword>
  <keyword>diastolic function</keyword>
  <keyword>cardiac fibrosis</keyword>
  <keyword>cardiac strain</keyword>
  <keyword>cardiac biomarker</keyword>
  <keyword>renal biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Cardio-Renal Syndrome</mesh_term>
    <mesh_term>Ventricular Dysfunction, Left</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exenatide</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>February 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT02251431/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Exenatide-extended Release</title>
          <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching placebo subcutaneously once per week x 38 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="28"/>
              </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>
      <population>A total of 57 patients were enrolled from November 2015 to December 2019. Despite original plan of enrolling 104 patients, the recruitment stopped early due to poor accrual</population>
      <group_list>
        <group group_id="B1">
          <title>Exenatide-extended Release</title>
          <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching placebo subcutaneously once per week x 38 weeks</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="29"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="57"/>
          </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="57.78" spread="12.83"/>
                    <measurement group_id="B2" value="55.17" spread="9.64"/>
                    <measurement group_id="B3" value="56.50" spread="11.35"/>
                  </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="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="30"/>
                  </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="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Galectin-3</title>
        <description>Mean change in plasma galectin-3 (pg/ml)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Galectin-3</title>
          <description>Mean change in plasma galectin-3 (pg/ml)</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9570.91" spread="4990.06"/>
                    <measurement group_id="O2" value="9266.7" spread="6032.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9539.21" spread="3893.04"/>
                    <measurement group_id="O2" value="8098.78" spread="6272.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>ST2</title>
        <description>Mean change in plasma ST2 (pg/ml)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>ST2</title>
          <description>Mean change in plasma ST2 (pg/ml)</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="635.2" spread="449.82"/>
                    <measurement group_id="O2" value="443.18" spread="380.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="524.68" spread="423.61"/>
                    <measurement group_id="O2" value="534.53" spread="302.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>NGAL</title>
        <description>Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>NGAL</title>
          <description>Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.35" spread="29.01"/>
                    <measurement group_id="O2" value="18.44" spread="25.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.01" spread="14.87"/>
                    <measurement group_id="O2" value="24.39" spread="40.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>KIM-1</title>
        <description>Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>KIM-1</title>
          <description>Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.08"/>
                    <measurement group_id="O2" value="0.13" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.13" spread="0.14"/>
                    <measurement group_id="O2" value="0.1" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>L-FABP</title>
        <description>Mean change in urine L-type fatty acid binding protein:Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>L-FABP</title>
          <description>Mean change in urine L-type fatty acid binding protein:Cr ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.61" spread="3.72"/>
                    <measurement group_id="O2" value="3.24" spread="4.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.05" spread="2.18"/>
                    <measurement group_id="O2" value="3" spread="2.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>IL-18</title>
        <description>Mean change in urine interleukin-18:Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>IL-18</title>
          <description>Mean change in urine interleukin-18:Cr ratio</description>
          <units>pg/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.68" spread="2.4"/>
                    <measurement group_id="O2" value="3.48" spread="4.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.96" spread="3.5"/>
                    <measurement group_id="O2" value="2.68" spread="2.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Alpha GST</title>
        <description>Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Alpha GST</title>
          <description>Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.2"/>
                    <measurement group_id="O2" value="0.67" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" spread="0.16"/>
                    <measurement group_id="O2" value="0.27" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Troponin I</title>
        <description>Mean change in plasma ultrasensitive troponin I (pg/ml)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Troponin I</title>
          <description>Mean change in plasma ultrasensitive troponin I (pg/ml)</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="230.85" spread="282.73"/>
                    <measurement group_id="O2" value="415.65" spread="446.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="238.53" spread="283.59"/>
                    <measurement group_id="O2" value="504.48" spread="599.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pi GST</title>
        <description>Mean change in pi glutathione S-transferase (piGST):Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Pi GST</title>
          <description>Mean change in pi glutathione S-transferase (piGST):Cr ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="3.41"/>
                    <measurement group_id="O2" value="3.99" spread="3.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.03" spread="5.67"/>
                    <measurement group_id="O2" value="4.27" spread="4.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>NAG</title>
        <description>Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>NAG</title>
          <description>Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.35" spread="29.01"/>
                    <measurement group_id="O2" value="18.44" spread="25.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.01" spread="14.87"/>
                    <measurement group_id="O2" value="24.39" spread="40.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cystatin-C</title>
        <description>Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Cystatin-C</title>
          <description>Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.07" spread="2.64"/>
                    <measurement group_id="O2" value="1.84" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.47" spread="1.22"/>
                    <measurement group_id="O2" value="1.57" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>BNP</title>
        <description>Mean change in plasma B-type natriuretic peptide BNP (pg/ml)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>BNP</title>
          <description>Mean change in plasma B-type natriuretic peptide BNP (pg/ml)</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.87" spread="9.3"/>
                    <measurement group_id="O2" value="9.88" spread="14.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.59" spread="9.59"/>
                    <measurement group_id="O2" value="14.02" spread="22.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>ACR</title>
        <description>Mean change in urine albumin:Cr ratio (ACR)</description>
        <time_frame>38 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Exenatide-extended Release</title>
            <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo subcutaneously once per week x 38 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>ACR</title>
          <description>Mean change in urine albumin:Cr ratio (ACR)</description>
          <units>ng/mmol Creat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6678.23" spread="12662.79"/>
                    <measurement group_id="O2" value="9713.65" spread="14380.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study (38th week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3963.49" spread="3101.13"/>
                    <measurement group_id="O2" value="9825.2" spread="9539.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>38 weeks from study initiation</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Exenatide-extended Release</title>
          <description>Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching placebo subcutaneously once per week x 38 weeks</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="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>NSTEMI (non ST elevated myocardial infarction)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </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="20" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal events, myalgia, fatigue</sub_title>
                <counts group_id="E1" events="61" subjects_affected="20" subjects_at_risk="29"/>
                <counts group_id="E2" events="107" subjects_affected="21" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="28" subjects_affected="15" subjects_at_risk="29"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Our recruitment stopped early due to low accrual rate. Hence, null findings may be a result of lack of statistical power. Accordingly, our results should be interpreted as hypothesis-generating.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Biostatistician</name_or_title>
      <organization>Baylor Scott &amp; White Research Institute</organization>
      <phone>8033190755</phone>
      <email>gelareh.rahimighazikalayeh@bswhealth.org</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/NCT02251431
org study id: 014-149
secondary id: D5551L00004/ISSEXEN0013
nct id: NCT02251431
lead sponsor: 
has dmc: Yes
Among adult individuals with type 2 diabetes mellitus and at risk for heart failure with
      impaired relaxation of the heart mildly reduced kidney filtration function (Type 4
      cardiorenal syndrome) this trial will evaluate the quantitative impact of 38 weeks of
      treatment with exenatide extended-release injections versus placebo. on a cardiac biomarker
      blood test score, cardiac fibrosis seen on magnetic resonance scanning, cardiac strain
      identified by ultrasonography and strain rate imaging, and a kidney urine biomarker score.
Primary Aim

      Among adult individuals with type 2 diabetes mellitus (T2DM) and at risk for diastolic heart
      failure (DHF) and mildly reduced renal filtration function (Type 4 cardiorenal syndrome), to
      evaluate the quantitative impact on the MISS (myocardial injury summary score) cardiac
      biomarker score, cardiac fibrosis by MRI, cardiac strain by ultrasonography and strain rate
      imaging, and KISS (kidney injury summary score) kidney biomarker score after 38 weeks of
      treatment with exenatide extended-release or placebo.

      Secondary Aim

      To evaluate the inter-relationships between demographic, clinical, and biochemical variables
      (MISS score, KISS score) and of progressive cardiac fibrosis as assessed by MRI, strain-rate
      imaging, and in adult individuals with T2DM and at risk for DHF (Type 4 cardiorenal
      syndrome).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Galectin-3
time frame: 38 weeks
description: Mean change in plasma galectin-3 (pg/ml)
measure: ST2
time frame: 38 weeks
description: Mean change in plasma ST2 (pg/ml)
measure: NGAL
time frame: 38 weeks
description: Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio
measure: KIM-1
time frame: 38 weeks
description: Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio
measure: L-FABP
time frame: 38 weeks
description: Mean change in urine L-type fatty acid binding protein:Cr ratio
measure: IL-18
time frame: 38 weeks
description: Mean change in urine interleukin-18:Cr ratio
measure: Alpha GST
time frame: 38 weeks
description: Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio
measure: Troponin I
time frame: 38 weeks
description: Mean change in plasma ultrasensitive troponin I (pg/ml)
measure: Pi GST
time frame: 38 weeks
description: Mean change in pi glutathione S-transferase (piGST):Cr ratio
measure: NAG
time frame: 38 weeks
description: Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio
measure: Cystatin-C
time frame: 38 weeks
description: Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)
measure: BNP
time frame: 38 weeks
description: Mean change in plasma B-type natriuretic peptide BNP (pg/ml)
measure: ACR
time frame: 38 weeks
description: Mean change in urine albumin:Cr ratio (ACR)
arm group label: Exenatide-extended release
arm group type: Experimental
description: Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo subcutaneously once per week x 38 weeks
intervention type: Drug
intervention name: BYDUREON
description: Exenatide-extended release, Cohorts A and B
arm group label: Exenatide-extended release
intervention type: Drug
intervention name: Placebo
description: Cohort A only
arm group label: Placebo
other name: Matching placebo subcutaneous injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter A McCullough, MD, MPH
role: Study Chair
affiliation: Baylor Research Institute
facility: 
country: United States
citation: Chinnaiyan KM, Alexander D, Maddens M, McCullough PA. Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. Am Heart J. 2007 Feb;153(2):189-200. doi: 10.1016/j.ahj.2006.10.022.
PMID: 17239676
citation: Davidson MH. Cardiovascular effects of glucagonlike peptide-1 agonists. Am J Cardiol. 2011 Aug 2;108(3 Suppl):33B-41B. doi: 10.1016/j.amjcard.2011.03.046.
PMID: 21802579
citation: Levine GD, Rosai J, Bearman RM, Polliack A. The fine structure of thymoma, with emphasis on its differential diagnosis. A study of ten cases. Am J Pathol. 1975 Oct;81(1):49-86.
PMID: 1080957
citation: Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA. Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011 Jan;34(1):90-5. doi: 10.2337/dc10-1393. Epub 2010 Oct 7.
PMID: 20929995
citation: McCullough PA, Olobatoke A, Vanhecke TE. Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med. 2011;12(4):200-10. doi: 10.3909/ricm0624. Erratum In: Rev Cardiovasc Med. 2012;13(1):e52.
PMID: 22249510
citation: Wang YC, Yu CC, Chiu FC, Tsai CT, Lai LP, Hwang JJ, Lin JL. Soluble ST2 as a biomarker for detecting stable heart failure with a normal ejection fraction in hypertensive patients. J Card Fail. 2013 Mar;19(3):163-8. doi: 10.1016/j.cardfail.2013.01.010.
PMID: 23482076
citation: Jellis C, Martin J, Narula J, Marwick TH. Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol. 2010 Jul 6;56(2):89-97. doi: 10.1016/j.jacc.2010.02.047.
PMID: 20620723
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Cardio-Renal Syndrome
mesh term: Ventricular Dysfunction, Left
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Exenatide
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Our recruitment stopped early due to low accrual rate. Hence, null findings may be a result of lack of statistical power. Accordingly, our results should be interpreted as hypothesis-generating.
point of contact: 