<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/NCT03029351</url>
  </required_header>
  <id_info>
    <org_study_id>1981 GLP</org_study_id>
    <nct_id>NCT03029351</nct_id>
  </id_info>
  <brief_title>GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes</brief_title>
  <acronym>1981</acronym>
  <official_title>GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University at Buffalo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective study to evaluate effect of Exenatide extended release treatment for 1&#xD;
      year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to&#xD;
      placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective study to evaluate effect of Exenatide extended release treatment for 1&#xD;
      year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to&#xD;
      placebo. The similarities in baseline values between the study groups will be compared using&#xD;
      appropriate parametric tests. Transformations of the data on order to meet statistical&#xD;
      assumptions may be considered. All statistical analysis will be carried out using SPSS&#xD;
      software (SPSS Inc, Chicago, Illinois) based on intention to treat principle. Data will be&#xD;
      presented as mean±standard error. The primary endpoint of the study is the change from&#xD;
      baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release&#xD;
      and placebo treatments. Fasting samples collected at weeks 0, 12, 26, 39 and 56 will be used&#xD;
      for this assessment with values at week 0 considered as baseline. Changes from baselines form&#xD;
      both drugs arms will be compared to those from the placebo arms in both the micro and&#xD;
      macroalbuminuria groups. The statistical analysis will be done using mixed model for repeated&#xD;
      measurement (MMRM) analysis with assigned α value of 0.05. Our preliminary data on&#xD;
      retrospective analysis of the difference in albuminuria following GLP-1RA treatment for 2.5&#xD;
      yrs in T2DM patients with micro and macroalbuminuria show regression of albuminuria (UACR) by&#xD;
      approximately 55mg/mg and 500mg/g (about 50% reduction), respectively. Conservatively&#xD;
      estimating a difference in the change from baseline in albuminuria after 1 year between the&#xD;
      Exenatide extended release and placebo groups (across both albuminuria groups) of 60mg/g,&#xD;
      with standard deviation of no more than 91mg/g, a sample size of 38 patients per group should&#xD;
      provide adequate power (beta = 0.2) to detect a significant difference (alpha = 0.05).&#xD;
      Assuming a drop-out rate of 15% and 2:1 drug:placebo randomization ratio, 60 active and 30&#xD;
      control will be recruited for a total of 90 patients (rounded up). Patients will be enrolled&#xD;
      based on a predetermined stratification according to the two albuminuria categories (micro&#xD;
      and macro at 1:1 ratio) with 45 patients in each.&#xD;
&#xD;
      The secondary end points include the comparison of the changes in albuminuria based on&#xD;
      baseline albuminuria category (micro or macro), creatinine clearance, Cystatin C, TGFβ, type&#xD;
      I and IV collagen, CTGF, and fibronectin levels, the expression of SMAD3, SMAD4, NQO-1,&#xD;
      GST-1P and HO-1, Nrf-2/keap-1 system activation between the Exenatide extended release and&#xD;
      placebo groups and across albuminuria categories&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    termination by sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">January 10, 2017</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">July 2019</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change from baseline in albuminuria levels</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in albuminuria category (micro or macro)</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change in albuminuria category between normal to micro to macro albuminuria at12, 26, 39, 56 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in creatinine clearance</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in creatinine at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in Cystatin C</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in cystatin C at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in TGFβ</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in TGFβ level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in type I and IV collagen</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in Type I and IV collagen levels at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CTGF</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in CTGF level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in fibronectin levels</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in fibronectin level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in the expression of SMAD3</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in SMAD3 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in SMAD4</measure>
    <time_frame>12 26, 39, 56 weeks</time_frame>
    <description>change from baseline in SMAD4 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in NQO-1</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in NQO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in GST-1P</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in GST-1P level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in HO-1</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in HO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Nrf-2/keap-1</measure>
    <time_frame>12, 26, 39, 56 weeks</time_frame>
    <description>change from baseline in Nrf-2/keap-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Type2 Diabetes</condition>
  <condition>Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Exenatide extended release</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to Exenatide extended release.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide Extended Release for Inj Susp 2 MG</intervention_name>
    <description>Exenatide extended release treatment weekly for 1 year in T2DM patients with micro- and macroalbuminuria</description>
    <arm_group_label>Exenatide extended release</arm_group_label>
    <other_name>Bydureon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo treatment weekly for 1 year in type 2 diabetes with micro-and macroalbuminuria</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 Diabetes for at least 1 year.&#xD;
&#xD;
          -  Microalbuminuria for at least 6 months (UACR: 30-300 mg/g)&#xD;
&#xD;
          -  Macroalbuminuria for at least 6 months (UACR: &gt;300 mg/g)&#xD;
&#xD;
          -  HbA1c of ≤10%&#xD;
&#xD;
          -  Ages 18-65 years (inclusive of ages 18 and 65)&#xD;
&#xD;
          -  On ARBs/ACEi for at &gt;3months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of GLP-1 Receptor agonists or SGLT-2 inhibitors therapy in the last 3 months&#xD;
&#xD;
          -  History or risk for pancreatitis (e.g., history of gallstones, alcohol abuse, and&#xD;
             hypertriglyceridemia)&#xD;
&#xD;
          -  Coronary event or procedure (myocardial infarction, unstable angina, coronary artery&#xD;
             bypass, surgery or coronary angioplasty) in the previous 3 months&#xD;
&#xD;
          -  Hepatic disease: Severe hepatic insufficiency and/or significant abnormal liver&#xD;
             function defined as:&#xD;
&#xD;
               1. Aspartate aminotransferase (AST) &gt;3x upper limit of normal (ULN) and/or alanine&#xD;
                  aminotransferase (ALT) &gt;3x ULN&#xD;
&#xD;
               2. Total bilirubin &gt;2.0 mg/dL (34.2 µmol/L)&#xD;
&#xD;
               3. Positive serologic evidence of current infectious liver disease including&#xD;
                  Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus&#xD;
                  antibody&#xD;
&#xD;
               4. Liver function tests more than 3 times the upper limit of normal&#xD;
&#xD;
          -  Renal impairment (serum eGFR &lt;30 ml/min)&#xD;
&#xD;
          -  HIV&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
&#xD;
          -  History of gastroparesis&#xD;
&#xD;
          -  History of medullary thyroid carcinoma or MEN 2 syndrome&#xD;
&#xD;
          -  Alcoholism&#xD;
&#xD;
          -  Hypertriglyceridemia (&gt;500 mg/dl).&#xD;
&#xD;
          -  Any other life-threatening, non-cardiac disease&#xD;
&#xD;
          -  Uncontrolled hypertension (BP &gt; 160/100 mm of Hg)&#xD;
&#xD;
          -  Congestive Heart Failure class III or IV&#xD;
&#xD;
          -  Use of an investigational agent or therapeutic regimen within 30 days of study&#xD;
&#xD;
          -  Participation in any other concurrent clinical trial&#xD;
&#xD;
          -  Pregnant or breastfeeding patients or females of childbearing age not on 2 forms of&#xD;
             acceptable contraceptives.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Diabetes Endocrinology Research Center of WNY</name>
      <address>
        <city>Williamsville</city>
        <state>New York</state>
        <zip>14221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University at Buffalo</investigator_affiliation>
    <investigator_full_name>Paresh Dandona</investigator_full_name>
    <investigator_title>SUNY Distinguished Professor</investigator_title>
  </responsible_party>
  <keyword>albuminuria</keyword>
  <keyword>GLP-1 Receptor Agonist</keyword>
  <keyword>Type 2 Diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Albuminuria</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03029351/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03029351
org study id: 1981 GLP
nct id: NCT03029351
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a prospective study to evaluate effect of Exenatide extended release treatment for 1
      year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to
      placebo.
This is a prospective study to evaluate effect of Exenatide extended release treatment for 1
      year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to
      placebo. The similarities in baseline values between the study groups will be compared using
      appropriate parametric tests. Transformations of the data on order to meet statistical
      assumptions may be considered. All statistical analysis will be carried out using SPSS
      software (SPSS Inc, Chicago, Illinois) based on intention to treat principle. Data will be
      presented as mean±standard error. The primary endpoint of the study is the change from
      baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release
      and placebo treatments. Fasting samples collected at weeks 0, 12, 26, 39 and 56 will be used
      for this assessment with values at week 0 considered as baseline. Changes from baselines form
      both drugs arms will be compared to those from the placebo arms in both the micro and
      macroalbuminuria groups. The statistical analysis will be done using mixed model for repeated
      measurement (MMRM) analysis with assigned α value of 0.05. Our preliminary data on
      retrospective analysis of the difference in albuminuria following GLP-1RA treatment for 2.5
      yrs in T2DM patients with micro and macroalbuminuria show regression of albuminuria (UACR) by
      approximately 55mg/mg and 500mg/g (about 50% reduction), respectively. Conservatively
      estimating a difference in the change from baseline in albuminuria after 1 year between the
      Exenatide extended release and placebo groups (across both albuminuria groups) of 60mg/g,
      with standard deviation of no more than 91mg/g, a sample size of 38 patients per group should
      provide adequate power (beta = 0.2) to detect a significant difference (alpha = 0.05).
      Assuming a drop-out rate of 15% and 2:1 drug:placebo randomization ratio, 60 active and 30
      control will be recruited for a total of 90 patients (rounded up). Patients will be enrolled
      based on a predetermined stratification according to the two albuminuria categories (micro
      and macro at 1:1 ratio) with 45 patients in each.

      The secondary end points include the comparison of the changes in albuminuria based on
      baseline albuminuria category (micro or macro), creatinine clearance, Cystatin C, TGFβ, type
      I and IV collagen, CTGF, and fibronectin levels, the expression of SMAD3, SMAD4, NQO-1,
      GST-1P and HO-1, Nrf-2/keap-1 system activation between the Exenatide extended release and
      placebo groups and across albuminuria categories
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: change from baseline in albuminuria levels
time frame: 12, 26, 39, 56 weeks
description: change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in albuminuria category (micro or macro)
time frame: 12, 26, 39, 56 weeks
description: change in albuminuria category between normal to micro to macro albuminuria at12, 26, 39, 56 weeks
measure: change in creatinine clearance
time frame: 12, 26, 39, 56 weeks
description: change from baseline in creatinine at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in Cystatin C
time frame: 12, 26, 39, 56 weeks
description: change from baseline in cystatin C at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in TGFβ
time frame: 12, 26, 39, 56 weeks
description: change from baseline in TGFβ level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in type I and IV collagen
time frame: 12, 26, 39, 56 weeks
description: change from baseline in Type I and IV collagen levels at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: Change in CTGF
time frame: 12, 26, 39, 56 weeks
description: change from baseline in CTGF level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in fibronectin levels
time frame: 12, 26, 39, 56 weeks
description: change from baseline in fibronectin level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in the expression of SMAD3
time frame: 12, 26, 39, 56 weeks
description: change from baseline in SMAD3 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in SMAD4
time frame: 12 26, 39, 56 weeks
description: change from baseline in SMAD4 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in NQO-1
time frame: 12, 26, 39, 56 weeks
description: change from baseline in NQO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in GST-1P
time frame: 12, 26, 39, 56 weeks
description: change from baseline in GST-1P level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: change in HO-1
time frame: 12, 26, 39, 56 weeks
description: change from baseline in HO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
measure: Change in Nrf-2/keap-1
time frame: 12, 26, 39, 56 weeks
description: change from baseline in Nrf-2/keap-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
arm group label: Exenatide extended release
arm group type: Experimental
description: Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to Exenatide extended release.
intervention type: Drug
intervention name: Exenatide Extended Release for Inj Susp 2 MG
description: Exenatide extended release treatment weekly for 1 year in T2DM patients with micro- and macroalbuminuria
arm group label: Exenatide extended release
other name: Bydureon
intervention type: Drug
intervention name: Placebo
description: placebo treatment weekly for 1 year in type 2 diabetes with micro-and macroalbuminuria
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University at Buffalo
investigator full name: Paresh Dandona
investigator title: SUNY Distinguished Professor
mesh term: Kidney Diseases
mesh term: Albuminuria
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Exenatide
sharing ipd: No
provided document: 