D

Phase 1

• Conditions: TYPE 2 DIABETES; MedDRA version: 20.0Level: SOCClassification code 10027433Term: Metabolism and nutrition disordersSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2016-003614-27-IT
• Lead Sponsor: IVERSITÀ CATTOLICA DEL SACRO CUORE- POLICLINICO A. GEMELLI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-08
• Last Update Posted: 12 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Female or male subjects aged between 40 and 75 inclusive.
? Patients who have been surgically sterilized (hysterectomy or tubal-ligation) at least 12 months prior to screening, or
? are postmenopausal having had no regular menstrual bleeding for at least one (1) year prior to screening. Menopause will be confirmed by a plasma follicle stimulating hormone (FSH) level of > 35 IU/mL at screening, or
? Women with childbearing potential willing not to start a pregnancy during the course of the study and non-nursing women
? Men having relationships with women with childbearing potential willing not to procure a pregnancy during the course of the study;
3. Patients with type 2 diabetes
4. Patients with established, stable CAD, defined as =30% coronary stenosis in at least one major coronary vessel on invasive coronary angiography (ICA) or computed tomography angiography (CTA) performed within 12 months from screening and no indication to revascularization
5. Patients with a clinical indication for 13N-ammonia PET-CT, as established by a cardiologist, nuclear medicine physician or diabetologists
6. Patients with a body mass index (BMI) equal or greater than 25 kg/m2 but less than 35 kg/m2 [BMI = Weight (kg) / Height squared (m2)]
7. Patients with a HbA1c between 7,5% and 8,5% according to the actual clinical conditions of the patients;
8. Patients with a diabetes duration <10 years;
9. Patients with stable medical therapy [including other anti-hyperglycemic agents (see Table 1, section 5.2.1 for all therapies allowed, as per current standard treatment); pioglitazone and basal-bolus insulin treatment are excluded, as reported in the exclusion criteria 15] for at least 3 months prior to the screening visit (including stable insulin dose defined as no variation more than 30% in daily insulin dose within the preceding 3 months,. The reference for the initial prescription of the insulin dose starts from the values described in Table 1, section 5.2.1,. and is then titrated on the metabolic assessment done for each patient).
10. Patients with Fasting C-peptide > 1 ng/mL (0.33 nmol/L) at Visit 0
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Type 1 diabetes (as assessed by medical history); previous diagnosis of Latent Autoimmune Diabetes of Adults (LADA), and or not fulfilling inclusion criteria #10
2. History of diabetic ketoacidosis or hyperosmolar non ketotic coma
3. NYHA class III or IV
4. Unstable angina
5. Previous re-vascularisation (either percutaneous coronary intervention or coronary artery bypass graft)
6. Reduced left ventricular ejection fraction (=50%)
7. Increased likelihood of developing diabetic ketoacidosis (history of DKA, alcohol consumption, volume depletion dehydration, clinical conditions causing diarrhea, vomit and anorexia)
8. Moderate to severe renal impairment (eGFR<60 ml/min/1.73m2 as calculated by the modification of diet in renal disease [MDRD] equation or end-stage renal disease); overt proteinuria, defined as Spot urine Microalbumin/Cr ratio of >300 mg/g at screening (Visit 0)
9. Severe liver dysfunction
10. Asthma
11. Uncontrolled blood pressure
12. Symptomatic tachy- or bradyarrhythmias
13. Previous acute myocardial infarction
14. Contraindications to adenosine: known hypersensitivity to adenosine or to any of the excipients; sick sinus syndrome, second or third degree atrio-ventricular block (except in patients with a functioning artificial pacemaker); chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma bronchiale); long QT syndrome; severe hypotension; decompensated states of heart failure
15. Use of pioglitazone; use of loop diuretics; basal-bolus insulin therapy; use of systemic steroids less than 3 days prior to the screening visit (Visit 0)
16. Known hypersensitivity to the active substance or to any of the excipients in study drug
17. Inability to provide informed consent
18. Participation in another clinical study with an investigational product during the previous 30 days
19. Patients with history of breast, bladder and prostate cancer
20. Patients will undergo to surgical procedures
21 Patients with acute urinary tract infection
22 Patients with history of intolerance to galactose and lactose
23. Severe/uncontrolled medical conditions, causing volume depletion

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to assess the effect of dapagliflozin on myocardial insulin sensitivity.;Secondary Objective: The secondary objective is to assess the global heart function, the metabolic systemic effects of dapagliflozin, and the glycemic control.;Primary end point(s): myocardial glucose uptake (MGU);Timepoint(s) of evaluation of this end point: 15 MONTHS

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Myocardial perfusion<br>• Systemic insulin sensitivity<br>• Pericardial fat<br>• Glycemic control<br>• Cardiac function<br>• Body weight<br>• Blood pressure<br>• Urinary output<br>• Urinary glucose output;Timepoint(s) of evaluation of this end point: 15 MONTHS