Effects of SGLT-2 inhibitor on heart function and metabolism in patients with Type 2 diabetes and high risk of heart disease cardiovascular: The SIMPle Randomized Clinical Trial

Phase 1

• Conditions: Type 2 diabetes and cardiovascular risk; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-003743-10-DK
• Lead Sponsor: Herlev og Gentofte Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-10-14
• Last Update Posted: 13 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

•T2 DM (WHO criteria), diagnosed at least 3 months prior to visit 0
•Patients with diabetes must be either untreated or treated with one or more oral anti-diabetic drugs, including incretin therapy, GLP-1 analogues or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs
•For patients on background therapy: stable dose of anti-diabetics within 30 days prior to baseline
•HbA1c of = 48 mmol/L and = 86 mmol/L at screening for patients on background therapy or HbA1c of = 48 mmol/L and = 75 mmol/L at screening for drug-naïve patients.
•BMI = 45 kg/m2 at screening
•Age =18 years
•Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study
•Able to understand the written patient information and to give informed consent

Patients must have high cardiovascular risk, defined as at least one of the following:
•Albuminuria ( albumin/creatinine ratio = 30 mg/g or plasma NT-proBNP = 70 pg/ml)
• Confirmed history of myocardial infarction (>2 months prior to baseline)
•Heart failure according to Framingham Heart Failure Criteria
•Patient discharged from hospital with a documented diagnosis of unstable angina within 12 months prior to baseline
•Evidence of coronary artery disease by CAG in 1 or more major coronary arteries
• A positive noninvasive stress test, or a positive stress echocardiography showing regional systolic wall motion abnormalities, or a positive scintigraphic test showing stress-induced ischemia,
• History of ischemic or haemorrhagic stroke (>2 months prior to informed consent)
• Presence of peripheral artery disease (symptomatic or not ) documented by either: previous limb angioplasty, stenting or bypass surgery; or previous limb or foot amputation due to circulatory insufficiency; or angiographic evidence of significant (> 50%) peripheral artery stenosis in at least one limb; or evidence from a non-invasive measurement of significant (>50% or as reported as hemodynamically significant) peripheral artery stenosis in at least one limb; or ankle brachial index of < 0.9

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

•Allergic to the study medication
•Treatment with SGLT-2 inhibitor within 1 months prior to baseline
•Impaired kidney function, eGFR = 30 ml/min
•Severe liver insufficiency (Child-Pugh class C)
•ECG showing malign ventricular arrhythmia or prolonged QT-interval (>500ms)
•Untreated clinical significant heart valve disease
•Planned cardiac surgery or angioplasty within 3 months.
•Myocardial infarction (MI) = 30 days prior to baseline
•Percutaneous coronary intervention (PCI) = 4 weeks prior to baseline
•History of coronary artery bypass graft (CABG) = 8 weeks prior to enrollment
•Prior history of heart transplantation
•Unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure < 90 or > 180 mmHg, respectively), sick sinus syndrome or > 1st degree atrioventricular block in the absence of a functioning pacemaker
•Requirement of emergent cardiac medical intervention or catheterization
•Treatment with theophylline, or theophylline containing medications
•History of known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
•Pregnancy or desire hereof or breastfeeding.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To examine the mechanism behind the cardioprotective effects of the SGLT-2 inhibitor empagliflozine in a population of type 2 diabetics at high cardiovascular risk.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint is change in myocardial flow reserve by Rb-82 PET.;Timepoint(s) of evaluation of this end point: From baseline to 13 weeks.<br>