Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2
Condition: Type 2 Diabetes Mellitus; Myocardial Fibrosis; Myocardial Inflammation
MeSH terms: Myocarditis; Diabetes Mellitus, Type 2; Fibrosis; Inflammation
Intervention: dapagliflozin; Placebo
Intervention description: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.; Placebo
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Screening
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind and placebo controlled cardiac MRI study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      There is an unmet need for Cardiovascular Disease (CVD) risk reduction in patients with Type
      2 Diabetes. In recent trials there has been promising findings of more effective glucose
      management and reductions in overall CVD events and hospitalization for heart failure with
      SGLT-2 inhibition. Using the capability of cardiac MRI with T1- and T2-mapping in assessments
      of myocardial fibrosis and inflammation, the investigators propose to conduct a clinical
      trial to investigate the effects of SGLT-2 inhibition with dapagliflozin on myocardial
      strain, fibrosis and inflammation as assessed by cardiac MRI with T1- and T2-mapping in
      patients with type-2 diabetes.

      Over approximately 12 months subjects will have 6 clinical visits at the investigators
      research clinic. During this time subjects will be randomized to receive either active 10mg
      dapagliflozin or a matching placebo. 2 MRI scans at one of the two University of Washington
      research imaging centers will take place. One at randomization and the second scan will occur
      approximately 12 months after the first scan.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women at least 18 years of age

          2. Subjects with type-2 diabetes history >=5 years

          3. HbA1C 7-10% with glucose control medications including insulin, metformin or
             sulfonylurea

          4. Medically stable

          5. Willing to participate and sign informed consent.

        Exclusion Criteria:

          1. Contraindication to MRI

          2. Currently or within last three months treatment with a SGLT2 inhibitor

          3. Currently taking glucagon-like peptide (GLP)-1 receptor antagonist

          4. Glomerular filtration rate (GFR) <60 mL/min/1.73 m2

          5. Unstable or rapidly progressive renal disease

          6. Hypotension with systolic blood pressure (SBP) <100 mmHg

          7. Hypersensitivity to dapagliflozin or any excipients

          8. Patients with severe hepatic impairment (Child-Pugh class C)

          9. Patients with active hepatitis B or C infection

         10. Any of the following CV/Vascular Diseases within 3 months prior to signing the consent
             at enrollment, as assessed by the investigator:

               1. Myocardial infarction

               2. Cardiac surgery or revascularization (CABG/PTCA)

               3. Unstable angina

               4. Heart Failure - New York Heart Association (NYHA) Class IV

               5. Transient ischemic attack (TIA) or significant cerebrovascular disease

               6. Unstable or previously undiagnosed arrhythmia

               7. Established peripheral artery disease (PAD)

        (18) Active bladder cancer (19) Recent episode of Diabetic ketoacidosis (DKA), frequent
        episodes of DKA (20) High risk of fractures, amputations and fibrosis (21) Women of
        child-bearing potential (ie, those who are not chemically or surgically sterilized or who
        are not post-menopausal) who have a positive pregnancy test at enrollment or randomization,
        OR women who are not willing to use a medically accepted method of contraception that is
        considered reliable in the judgment of the investigator, from the time of signing the
        informed consent until two weeks after the last dose of study drug, OR women who are
        breast-feeding.