Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at High Cardiovascular Risk: The SIMPle Randomized Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Empagliflozin
- Conditions
- Type2 Diabetes Mellitus
- Sponsor
- Caroline M Kistorp
- Enrollment
- 92
- Locations
- 1
- Primary Endpoint
- Rb-82 PET
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
Patients with type 2 diabetes (T2 DM) have a markedly increased risk of heart disease and it is estimated that, in the danish population, up 80% percent of patients with type 2 diabetes die from heart disease.
The sodium glucose cotransport-2 (SGLT-2) inhibitors were developed as an anti-diabetic therapy reducing blood glucose and weight by decreasing glucose reabsorption in the kidneys, leading to glucose excretion via the urine. However, in 2015 the EMPA-REG study showed that treatment with the SGLT-2 inhibitor empagliflozin significantly reduced the cardiovascular mortality and risk of admission under the diagnosis of heart failure in a population of patients with type 2 diabetes in addition to other risk factors for heart disease. The mechanism behind this surprising result is unknown and warrants further study.
The primary hypothesis of the present study is that treatment with empagliflozin improves the function and blood supply of the heart muscle cells in patients with type 2 diabetes and high risk of heart disease. The investigators will test this hypothesis by enrolling 92 participants with type 2 diabetes and other risk factors for heart disease, and treating them with either empagliflozin or a placebo. During the study period the investigators will monitor the effects of the treatment with various techniques such as heart scans using CT and ultrasound, measurements of the fluid pressures in the heart chambers, body composition measurements and a variety of relevant blood test.
Investigators
Caroline M Kistorp
Principal Investigator
Herlev and Gentofte Hospital
Eligibility Criteria
Inclusion Criteria
- •A diagnosis of type 2 diabetes mellitus at least 3 months prior to baseline visit
- •For patients on background therapy: stable dose of anti-diabetics within 30 days prior to baseline
- •HbA1c of ≥6.5% and ≤10% at screening for patients on background therapy or HbA1c of ≥6.5 % and ≤ 9.0% 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)
Exclusion Criteria
- •Allergic to the study medication
- •Treatment with SGLT-2 inhibitor within 3 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
Arms & Interventions
Empagliflozin
Empagliflozin, coated tablets, 25mg, once daily, for 13 weeks
Intervention: Empagliflozin
Placebo
Placebo, coated tablets, once daily, for 13 weeks
Intervention: Placebo Oral Tablet
Outcomes
Primary Outcomes
Rb-82 PET
Time Frame: 13 weeks
Between group difference in the change in myocardial flow reserve (MFR) by Rb-82 PET. Measured as change in global perfusion from rest to adenosine-induced stress.
Invasive hemodynamics
Time Frame: 13 weeks
Substudy, performed on 38 participants from the main group. Using right heart catheterisation to measure between group difference in the change in pulmonary capillary weight pressure (PCWP) at 25 watts (supine bicycle ergometer)
Secondary Outcomes
- Pulse wave analysis(13 weeks)
- DEXA(13 weeks)
- Echocardiography(13 weeks)
- Invasive hemodynamics - continued(13 weeks)
- GFR(13 weeks)
- U-alb/crea(13 weeks)
- 24 hour BP(13 weeks)
- Biomarkers(13 weeks)
- Questionnaires, continued(13 weeks)
- Insulin resistance(13 weeks)
- Daily activity(13 weeks)
- Questionnaires(13 weeks)
- Adipose tissue(13 weeks)