A Double-blind, Randomized, Parallel Group, Phase IV Study to Investigate the Effects of DAPAgliflozin on CARDiac Substrate Uptake, Myocardial Efficiency and Myocardial Contractile Work in Type 2 Diabetes Patients
Overview
- Phase
- Phase 4
- Intervention
- placebo
- Conditions
- Diabetes Mellitus Type 2
- Sponsor
- AstraZeneca
- Enrollment
- 53
- Locations
- 1
- Primary Endpoint
- Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief 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.
Detailed Description
The following will be assessed at Baseline and at the end of the treatment period; 1. MRI scanning in order to assess cardiac function and morphology. The MRI scanning will be made after fasting for at least 6 hours in the same time of day at all visits. The cardiac MRI examination will be performed in accordance with a pre-defined MRI protocol, with the total scan time at each visit estimated to 45 minutes. Images from all sites will be analyzed centrally at the core-lab using a dedicated software package and certified analysts. 2. CT-PET scanning will be made to assess myocardial function and metabolism, as well as fatty acid metabolism in brain, liver and kidney cortex. The CT-PET scanning will be made after a fast as well as abstinence from nicotine, alcohol and caffeine for at least 6 hours at the same time of day at all visits. * A cardiac 11C-Acetate PET/CT examination is performed (IV 400 MBq 11C-Acetate). * A cardiac 18F-FTHA PET/CT examination is performed (IV 150 MBq 18F-FTHA). The subject is further examined by PET/CT over the liver, kidney cortex and brain (in this order) for uptake of 18F-FTHA. Arterialized venous samples are acquired throughout to assess P-NEFA and 18F-FTHA metabolism by metabolite analysis
Investigators
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:
- •Atrial fibrillation, or other unstable or severe arrhythmia affecting heart function
- •Unstable heart failure or any heart failure with NYHA class III and IV
- •Significant valvular disease
- •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.
Arms & Interventions
placebo
placebo tablets once daily
Intervention: placebo
dapagliflozin 10mg
dapagliflozin 10mg tablets once daily
Intervention: dapagliflozin
Outcomes
Primary Outcomes
Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.
Time Frame: Baseline (Day 1) and end of treatment (Day 42)
Patients underwent magnetic resonance imaging (MRI) examination to determine the GLSLV, which is expressed as a percentage. The least square mean (LSM) change from baseline estimates were generated from an analysis of covariance (ANCOVA) model with treatment and baseline value of the endpoint as covariates.
Secondary Outcomes
- Adjusted Mean Change From Baseline in Myocardial Efficiency at End of Treatment.(Baseline (Day 1) and end of treatment (Day 42))