<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/NCT02998970</url>
  </required_header>
  <id_info>
    <org_study_id>REB# 15-402</org_study_id>
    <nct_id>NCT02998970</nct_id>
  </id_info>
  <brief_title>Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes</brief_title>
  <acronym>EMPA-HEART</acronym>
  <official_title>Effects of Empagliflozin on Cardiac Structure, Function, and Circulating Biomarkers in Patients With Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Unity Health Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effects of Empagliflozin on cardiac structure,&#xD;
      function and circulating biomarkers in patients with Type II diabetes. Empagliflozin&#xD;
      (anti-hyperglycemic agent), approved by Health Canada and the FDA for the treatment of Type&#xD;
      II diabetes, demonstrated a reduction in cardiovascular deaths and heart failure from a&#xD;
      previous post-marketing clinical trial. The use of empagliflozin to treat patients with&#xD;
      diabetes and heart disease has been approved by Health Canada. However, the process by which&#xD;
      it may give this beneficial effect remains unclear and needs further investigation.&#xD;
      Therefore, the aim of this study is to provide a fundamental understanding of the mechanistic&#xD;
      basis by which Empagliflozin could provide its potential cardio-protective effects by&#xD;
      employing the use of Cardiac Magnetic Resonance Imaging (CMRI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prevalence of heart failure in Canada is high, affecting 1-3% of total population,&#xD;
      representing one of the health care system's most expensive diagnoses. Type 2 diabetes is a&#xD;
      significant risk factor for heart disease, and the presence of both type 2 diabetes and heart&#xD;
      disease increases the risk of other major health complications including death. A&#xD;
      translational study is fundamental in understanding of the potential mechanistic basis of&#xD;
      empagliflozin's cardiac benefit.&#xD;
&#xD;
      The study drug, empagliflozin (marketed as Jardiance), belongs to a class of medications that&#xD;
      lowers blood glucose (sugar) by preventing glucose from entering back into blood circulation&#xD;
      and ensures it is eliminated in urine. It is approved by the FDA and Health Canada for the&#xD;
      treatment of type 2 diabetes.&#xD;
&#xD;
      This is a double-blind, randomized, placebo-controlled, parallel-group phase IV study of&#xD;
      empagliflozin vs. placebo in patients with type 2 diabetes with inadequate glycemic control&#xD;
      and at high cardiovascular risk. The purpose is to better understand how empagliflozin could&#xD;
      potentially improve heart function with the use of CMRI. Patients who have given informed&#xD;
      consent will undergo a baseline CMRI and will then be randomly assigned in a 1:1 basis to&#xD;
      either empagliflozin 10 mg once daily (OD) or matching placebo. The aim of the study is to&#xD;
      consent 90 eligible subjects, who will be followed for 26 weeks. An end of study CMRI will be&#xD;
      performed at 26 weeks.&#xD;
&#xD;
      The study is comprised of 6 study visits and enrolled subjects will be followed for 6 months.&#xD;
      The patients will be assessed using CMRI, which is considered the &quot;gold standard&quot; for&#xD;
      measuring left ventricular (LV) volume, mass, and ejection fraction. Patients will undergo&#xD;
      two CMRI examinations: at baseline and 6 months after surgery.&#xD;
&#xD;
      In addition, the investigators will be investigating changes from baseline in LV&#xD;
      end-diastolic volume, end-systolic volume, LV ejection fraction, regional LV diastolic and&#xD;
      systolic function, aortic pulse wave velocity and distensibility (as measures of arterial&#xD;
      stiffness) via CMR imaging in patients with type 2 diabetes treated with empagliflozin&#xD;
      compared to those who receive placebo. Also, changes from baseline on a panel of biomarkers&#xD;
      involved in the pathophysiology of heart will be evaluated at baseline, 1 months and 6&#xD;
      months, in patients with type 2 diabetes treated with empagliflozin.&#xD;
&#xD;
      Study assessments and potential adverse events reporting will be undertaken at each study&#xD;
      visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">September 2018</completion_date>
  <primary_completion_date type="Anticipated">September 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>Diagnostic</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Left Ventricular (LV) mass Changes</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in Left Ventricular (LV) mass (indexed to BSA) at 6 months in patients with Type 2 diabetes who receive empagliflozin vs. placebo.&#xD;
This will be measured using CMRI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>LV end-diastolic volume</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in LV end-diastolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.&#xD;
This will be measured using CMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>End-systolic volume (indexed to BSA)</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in end-systolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.&#xD;
This will be measured using CMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Ejection Fraction (LVEF)</measure>
    <time_frame>6 months</time_frame>
    <description>Changes LVEF at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.&#xD;
This will be measured using CMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional LV diastolic function</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in Regional LV diastolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.&#xD;
This will be measured using CMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional LV systolic function</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in Regional LV systolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.&#xD;
This will be measured using CMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aortic pulse wave velocity and distensibility</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in aortic pulse wave velocity and distensibility (as arterial stiffness) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>6 months</time_frame>
    <description>Changes on a panel of biomarkers involved in the pathophysiology of heart failure at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma catecholamine levels</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in plasma catecholamine levels at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">97</enrollment>
  <condition>Diabetes</condition>
  <condition>Cardiovascular Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo group acts as a control group. This is in order to objectively isolate empagliflozin's effect on cardiac structure and function as determined by CMR imaging.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Empagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The study medication (Jardiance) is the only diabetes medication to show a significant reduction in both cardiovascular risk and cardiovascular death. The generic name is empagliflozin and will be provided by Boehringer-Ingelheim. If the patient is randomized into the study drug group patients will receive empagliflozin 10 mg tablets once daily for a duration of 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Empagliflozin</intervention_name>
    <description>single oral tablet once daily.</description>
    <arm_group_label>Empagliflozin</arm_group_label>
    <other_name>Jardiance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>single oral tablet once daily.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects ≥40 and ≤ 80 years of age&#xD;
&#xD;
          -  History of type 2 diabetes&#xD;
&#xD;
          -  Haemoglobin A1C ≥6.5 and ≤10 % within 3 months of the Screening Visit&#xD;
&#xD;
          -  Established cardiovascular disease, defined as previous myocardial infarction ≥ 6&#xD;
             months ago, or previous coronary revascularization ≥ 2 months ago&#xD;
&#xD;
          -  Any background antihyperglycemic therapy (which has been stable for at least 2 months)&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent aspects of the trial&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests and&#xD;
             other trial procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are pregnant, lactating or of child bearing potential, or&#xD;
             pre-menopausal women. (Menopause will be determined by patient and physician history)&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Subjects currently treated with SGLT2 inhibitors, Glucagon-like peptide-1 (GLP1)&#xD;
             receptor agonist, or saxagliptin&#xD;
&#xD;
          -  Frequent episodes (&gt;4/month) of moderate hypoglycaemia, as defined by the Canadian&#xD;
             Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and&#xD;
             Management of Diabetes&#xD;
&#xD;
          -  Any episode of severe hypoglycaemia within the past 12 months, as also defined by the&#xD;
             Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and&#xD;
             Management of Diabetes&#xD;
&#xD;
          -  Subjects in whom coronary revascularisation by either Percutaneous coronary&#xD;
             intervention (PCI) or bypass surgery is being contemplated within 6 months, or who&#xD;
             have undergone revascularisation in the prior 2 months&#xD;
&#xD;
          -  Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate&#xD;
             (eGFR)&lt; 60 ml/min/1.73 m2 at screening&#xD;
&#xD;
          -  Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the&#xD;
             formulations&#xD;
&#xD;
          -  Subjects currently experiencing any clinically significant or unstable medical&#xD;
             condition that might limit their ability to complete the study, or to comply with the&#xD;
             requirements of the protocol, including: dermatologic disease, haematological disease,&#xD;
             pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease,&#xD;
             endocrine disease, neurological disease and psychiatric disease&#xD;
&#xD;
          -  Any malignancy not considered cured (except basal cell carcinoma of the skin). A&#xD;
             subject is considered cured if there has been no evidence of cancer recurrence for the&#xD;
             5 years prior to screening&#xD;
&#xD;
          -  Blood donation within 4 weeks prior to screening, or stated intention to donate blood&#xD;
             or blood products during the period of the study or within one month following&#xD;
             completion of the study&#xD;
&#xD;
          -  Subjects who have participated in studies of an investigational drug or device within&#xD;
             30 days prior to the screening visit&#xD;
&#xD;
          -  Conditions preventing safe MRI imaging such as the subject's weight exceeding 500 lbs;&#xD;
             maximum body dimension from side-to-side exceeding 70 cm and from back to front of&#xD;
             torso exceeding 50 cm or the presence of metallic fragments, clips or devices&#xD;
&#xD;
          -  LVEF &lt;30% on the most recent assessment within 6 months&#xD;
&#xD;
          -  New York Heart Association (NYHA) Class IV or recent hospitalization for decompensated&#xD;
             Heart Failure (HF) (&lt;3 months)&#xD;
&#xD;
          -  Unstable coronary syndromes&#xD;
&#xD;
          -  Moderate or severe aortic stenosis&#xD;
&#xD;
          -  Moderate or severe aortic regurgitation&#xD;
&#xD;
          -  Moderate or severe mitral stenosis&#xD;
&#xD;
          -  Moderate or severe mitral regurgitation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiovascular Disease</keyword>
  <keyword>Type 2 Diabetes</keyword>
  <keyword>Cardiac Magnetic Resonance Imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</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>Empagliflozin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02998970
org study id: REB# 15-402
nct id: NCT02998970
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the effects of Empagliflozin on cardiac structure,
      function and circulating biomarkers in patients with Type II diabetes. Empagliflozin
      (anti-hyperglycemic agent), approved by Health Canada and the FDA for the treatment of Type
      II diabetes, demonstrated a reduction in cardiovascular deaths and heart failure from a
      previous post-marketing clinical trial. The use of empagliflozin to treat patients with
      diabetes and heart disease has been approved by Health Canada. However, the process by which
      it may give this beneficial effect remains unclear and needs further investigation.
      Therefore, the aim of this study is to provide a fundamental understanding of the mechanistic
      basis by which Empagliflozin could provide its potential cardio-protective effects by
      employing the use of Cardiac Magnetic Resonance Imaging (CMRI).
The prevalence of heart failure in Canada is high, affecting 1-3% of total population,
      representing one of the health care system's most expensive diagnoses. Type 2 diabetes is a
      significant risk factor for heart disease, and the presence of both type 2 diabetes and heart
      disease increases the risk of other major health complications including death. A
      translational study is fundamental in understanding of the potential mechanistic basis of
      empagliflozin's cardiac benefit.

      The study drug, empagliflozin (marketed as Jardiance), belongs to a class of medications that
      lowers blood glucose (sugar) by preventing glucose from entering back into blood circulation
      and ensures it is eliminated in urine. It is approved by the FDA and Health Canada for the
      treatment of type 2 diabetes.

      This is a double-blind, randomized, placebo-controlled, parallel-group phase IV study of
      empagliflozin vs. placebo in patients with type 2 diabetes with inadequate glycemic control
      and at high cardiovascular risk. The purpose is to better understand how empagliflozin could
      potentially improve heart function with the use of CMRI. Patients who have given informed
      consent will undergo a baseline CMRI and will then be randomly assigned in a 1:1 basis to
      either empagliflozin 10 mg once daily (OD) or matching placebo. The aim of the study is to
      consent 90 eligible subjects, who will be followed for 26 weeks. An end of study CMRI will be
      performed at 26 weeks.

      The study is comprised of 6 study visits and enrolled subjects will be followed for 6 months.
      The patients will be assessed using CMRI, which is considered the "gold standard" for
      measuring left ventricular (LV) volume, mass, and ejection fraction. Patients will undergo
      two CMRI examinations: at baseline and 6 months after surgery.

      In addition, the investigators will be investigating changes from baseline in LV
      end-diastolic volume, end-systolic volume, LV ejection fraction, regional LV diastolic and
      systolic function, aortic pulse wave velocity and distensibility (as measures of arterial
      stiffness) via CMR imaging in patients with type 2 diabetes treated with empagliflozin
      compared to those who receive placebo. Also, changes from baseline on a panel of biomarkers
      involved in the pathophysiology of heart will be evaluated at baseline, 1 months and 6
      months, in patients with type 2 diabetes treated with empagliflozin.

      Study assessments and potential adverse events reporting will be undertaken at each study
      visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Double (Participant, Investigator)
measure: Left Ventricular (LV) mass Changes
time frame: 6 months
description: Changes in Left Ventricular (LV) mass (indexed to BSA) at 6 months in patients with Type 2 diabetes who receive empagliflozin vs. placebo.
This will be measured using CMRI.
measure: LV end-diastolic volume
time frame: 6 months
description: Changes in LV end-diastolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
This will be measured using CMRI.
measure: End-systolic volume (indexed to BSA)
time frame: 6 months
description: Changes in end-systolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
This will be measured using CMRI.
measure: Left Ventricular Ejection Fraction (LVEF)
time frame: 6 months
description: Changes LVEF at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
This will be measured using CMRI.
measure: Regional LV diastolic function
time frame: 6 months
description: Changes in Regional LV diastolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
This will be measured using CMRI.
measure: Regional LV systolic function
time frame: 6 months
description: Changes in Regional LV systolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
This will be measured using CMRI.
measure: Aortic pulse wave velocity and distensibility
time frame: 6 months
description: Changes in aortic pulse wave velocity and distensibility (as arterial stiffness) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
measure: Biomarkers
time frame: 6 months
description: Changes on a panel of biomarkers involved in the pathophysiology of heart failure at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.
measure: Plasma catecholamine levels
time frame: 6 months
description: Changes in plasma catecholamine levels at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo group acts as a control group. This is in order to objectively isolate empagliflozin's effect on cardiac structure and function as determined by CMR imaging.
arm group label: Empagliflozin
arm group type: Active Comparator
description: The study medication (Jardiance) is the only diabetes medication to show a significant reduction in both cardiovascular risk and cardiovascular death. The generic name is empagliflozin and will be provided by Boehringer-Ingelheim. If the patient is randomized into the study drug group patients will receive empagliflozin 10 mg tablets once daily for a duration of 6 months.
intervention type: Drug
intervention name: Empagliflozin
description: single oral tablet once daily.
arm group label: Empagliflozin
other name: Jardiance
intervention type: Drug
intervention name: Placebo
description: single oral tablet once daily.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Empagliflozin
sharing ipd: No