Effects of SGLT2 Inhibition on Myocardial Insulin Sensitivity

  • STATUS
    Recruiting
  • End date
    Dec 1, 2022
  • participants needed
    52
  • sponsor
    Andrea Giaccari
Updated on 16 March 2021

Summary

A Phase III, single-centre, randomized, 2-arm, parallel-group, double blind, placebo-controlled study, consisting of a screening phase (Days -14 to -1), a 4-week double-blind, placebo-controlled treatment phase and a 4-week follow-up phase.

Subjects: Type 2 diabetic patients and coronary artery diseases (CAD) not requiring revascularization or underwent percutaneous coronary intervention (PCI) but clinically stable at time of screening visit, with suboptimal glycaemic control (HbA1c 7.0-8.5%) on their current anti-hyperglycaemic regimen

Subjects will be randomized in a 1:1 ratio to dapagliflozin or placebo.

Subjects will undergo screening assessment in the 14-day period preceding administration of the first dose of study drug on Day 1.

The primary Objective is to assess the effect of dapagliflozin on myocardial insulin sensitivity The Secondary Objective is to assess global heart function, and metabolic systemic effects of dapagliflozin, and glycemic control.

The study aims to enroll patients with type 2 diabetes with suboptimal glycemic control, and with coronary artery diseases (CAD) not requiring revascularization or underwent percutaneous coronary intervention (PCI) but clinically stable, who have already undergone, under routine cardiological assessment, a positron emission tomography (PET) 13NH3 scan in order to assess the cardiovascular function. Thus, the study aims to assess whether the improvement in cardiac metabolism obtained with dapagliflozin is greater than that obtained with normal clinical practice (according to Standards of Care).

Details
Condition Type2 Diabetes Mellitus, Stable Coronary Artery Disease
Treatment Placebo, Dapagliflozin 10Mg Tab
Clinical Study IdentifierNCT03313752
SponsorAndrea Giaccari
Last Modified on16 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 40 yrs and 75 yrs?
Gender: Male or Female
Do you have any of these conditions: Stable Coronary Artery Disease or Type2 Diabetes Mellitus?
Do you have any of these conditions: Type2 Diabetes Mellitus or Stable Coronary Artery Disease?
Do you have any of these conditions: Stable Coronary Artery Disease or Type2 Diabetes Mellitus?
Provision of informed consent prior to any study-specific procedures
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 initiate 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
\. Patients with type 2 diabetes
\. 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 or with no evidence of
\. Patients with a clinical indication for 13N-ammonia PET-CT, as established
critical restenosis, if previously subjected to percutaneous coronary
by a cardiologist, nuclear medicine physician or diabetologist
intervention (PCI) (>6months)
\. 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)]
clinical conditions of the patients
\. Patients with diabetes duration <10 years
\. Patients with a HbA1c between 7.0% and 8.5%, according to the actual
\. 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
\. Patients with Fasting C-peptide > 1 ng/mL (0.33 nmol/L) at Visit 0

Exclusion Criteria

Type 1 diabetes (as assessed by medical history); previous diagnosis of Latent Autoimmune Diabetes of Adults (LADA), and or not fulfilling inclusion criteria #10
History of diabetic ketoacidosis or hyperosmolar non-ketotic coma
NYHA class III or IV
Unstable angina
Reduced left ventricular ejection fraction ( 50%)
Increased likelihood of developing diabetic ketoacidosis (history of DKA, alcohol consumption, volume depletion dehydration, clinical conditions causing diarrhea, vomit and anorexia)
Previous re-vascularisation (either percutaneous coronary intervention or coronary artery bypass graft) in the last <6 months before screening
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)
Severe liver dysfunction
Asthma
Uncontrolled blood pressure
Symptomatic tachy- or bradyarrhythmias
Previous acute myocardial infarction
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. bronchial asthma ); long QT syndrome; severe hypotension; decompensated states of heart failure
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)
Known hypersensitivity to the active substance or to any of the excipients in study drug
Inability to provide informed consent
Participation in another clinical study with an investigational product during the previous 30 days
Patients with history of breast, bladder and prostate cancer
Severe/uncontrolled medical conditions, causing liquid volume depletion
Patients who will undergo surgical procedures
Patients with acute urinary tract infection
Patients with history of intolerance to galactose and lactose
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