A Clinical Study to Investigate the Effects of Dapagliflozin on Heart Work, Heart Nutrient Uptake, and Heart Muscle Efficiency in Type 2 Diabetes Patients
Condition: Diabetes Mellitus Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: dapagliflozin; placebo
Intervention description: dapagliflozin 10mg; placebo to match dapagliflozin
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 53.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a randomised, placebo-controlled, double-blind, parallel-group, international,
      multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate
      uptake, myocardial efficiency and myocardial contractile work in T2D patients. Eligible
      subjects with T2D before randomisation and fulfilling all of the inclusion criteria and none
      of the exclusion criteria will be randomised in a 1:1 ratio to dapagliflozin 10 mg or placebo
      once daily and treated for six weeks. The study includes five visits.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol.

          -  Provision of signed and dated, written informed consent form prior to any mandatory
             study specific procedures, sampling, and analyses.

          -  Females or males ≥40 years up to 75 years of age.

          -  Individuals with type 2 diabetes diagnosed for at least 6 months based on the American
             Diabetes Association standards (ADA, 2017) and on stable dose of metformin for at
             least 6 weeks prior to screening and HbA1c at screening visit of ≥42 mmol/mol (6.0%)
             and ≤75 mmol/mol (9.0%) measured at local hospital laboratory.

          -  No significant signs or symptoms of coronary artery disease or, if known coronary
             artery disease, currently free of symptoms and a) all major epicardial vessels with
             <50% stenosis within 12 months prior to screening, or b) if revascularized with all
             major epicardial vessels with <50% remaining stenosis after stenting or bypass surgery
             procedure determined between 3 and 12 months prior to screening.

          -  Normal left ventricular ejection fraction (≥50%) assessed within 1 year prior to
             informed consent, and if applicable, after most recent acute episode of coronary
             artery syndrome, or at screening visit.

          -  Body mass index (BMI) ≥ 25 kg/m2.

        Exclusion Criteria:

          -  Blood pressure at screening that would require a change in blood pressure treatment
             over the study period or any of the following: systolic blood pressure >160 mmHg or
             diastolic blood pressure >100 mmHg.

          -  History of stroke or other clinically significant cerebrovascular disease.

          -  Any of the following cardiovascular diseases known within 3 months prior to signing
             the consent at enrolment:

               1. Atrial fibrillation, or other unstable or severe arrhythmia affecting heart
                  function

               2. Unstable heart failure or any heart failure with NYHA class III and IV

               3. Significant valvular disease

               4. Significant peripheral artery disease

          -  Planned cardiac surgery or angioplasty within 3 months from enrolment.

          -  Clinical diagnosis of type 1 diabetes, maturity onset diabetes of the young (MODY),
             secondary diabetes or diabetes insipidus.

          -  Verified body weight variability of >3 kg during the 3 proceeding months before
             screening.

          -  Active malignancy requiring treatment at the time of visit 1 (with the exception of
             successfully treated basal cell or treated squamous cell carcinoma).

          -  Patients with severe hepatic impairment (Child-Pugh class C).

          -  Unstable or rapidly progressing renal disease.

          -  Clinically significant disease or disorder which, in the opinion of the investigator,
             may either put the subject at risk because of participation in the study, or influence
             the results or the subject's ability to participate in the study.

          -  Ongoing treatment with other antidiabetic drugs than metformin.

          -  Ongoing treatment with loop diuretics.

          -  Ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.

          -  Contraindications to dapagliflozin therapy.

          -  Ongoing treatment with systemic steroids at time of informed consent or change in
             dosage of thyroid hormones within 6 weeks prior to informed consent or any other
             uncontrolled endocrine disorder except for T2D.

          -  Previous enrolment in the present study or participation in another clinical study
             with an investigational product during the last 1 month prior to screening.

          -  Estimated Glomerular Filtration Rate (eGFR) <45 mL/min/1.73 m2.

          -  Alcohol or drug abuse within the 3 months prior to informed consent that would
             interfere with trial participation or any ongoing condition leading to a decreased
             compliance to study procedures or study treatment intake.

          -  Any condition when MRI and CT-PET is contraindicated such as, but not limited to,
             having a metallic implant (such as pacemaker or cochlear implant), permanent make up,
             claustrophobia or BMI ≥40 kg/m2).

          -  Involvement in the planning and/or conduct of the study.

          -  Plasma donation within one month of screening or any blood donation/blood loss >450 mL
             during the 3 months prior to screening.

          -  Women who has a positive pregnancy test at enrolment or randomization, or are
             breastfeeding.