Value of SGLT2 Inhibitor (Dapagliflozin) as an Added Therapy in Diabetic Patients With Heart Failure With Reduced Ejection Fraction; Randomized Controlled Clinical Trial
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Damanhour University
- Enrollment
- 60
- Primary Endpoint
- LV dimensions
Study Overview
Brief Summary
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). Whereas the prevalence of HF in the general population is 1-4%, it reaches approximately 12% in T2DM patients. In 1972, Rubler reported a specific diabetes-associated cardiac injury called diabetic cardiomyopathy. This cardiomyopathy is defined by ventricular dysfunction occurring without coronary disease or hypertension. Diabetic cardiomyopathy is also characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis.
A large body of work indicates that diabetic cardiomyopathy is associated with altered cardiac energy metabolism. Indeed, in obese T2DM patients, heart lipid uptake is increased. Several studies support that free fatty acid (FFA) accumulation leads to the increased production of diacylglycerol (DAG), ceramides and reactive oxygen species (ROS), affecting cardiac insulin sensitivity and cardiac contractility. On the other hand, hyperglycemia and glucose overload have been involved in cardiac hypertrophy and dysfunction in the context of T2DM and obesity. The diabetic heart is simultaneously characterized by impaired insulin-stimulated glucose uptake and obvious signs of glucose overload, such as ROS and advanced glycation end-product (AGE) production as well as hexosamine pathway chronic activation. Interestingly, when comparing diabetic and nondiabetic obese patients, we previously demonstrated that hyperglycemia per se plays a central role in the impaired cardiac mitochondrial activity associated with myocardial contractile dysfunction.
Detailed Description
Primary Objective: The purpose of this study was to investigate the effect of Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2, on cardiovascular Cardiomyopathy, morbidity and mortality in patients with type 2 diabetes.
Secondary Objective: Change in the fibrosis and oxidative stress markers and its relation with progression of cardiomyopathy.
Proposal Steps
- Ethical committee approval will be obtained from Ethics committee of Faculty of Medicine, Elmenoufia University.
- This study will be registered at ClinicalTrials.gov after ethical committee approval .
- All participants should agree to take part in this clinical study and will provide informed consent.
- 60 participants who are Type 2 Diabetes and HFrEF Patients will be recruited from the Elmenoufia Hospital, Cardiology department, Elmenoufia University,
- The 60 participants will be randomly assigned into 2 groups:
- Control groups: receives the standard therapy for DM &HFrEF.
- The second group: receive 10mg tabs of Dapagliflozin ( Forxiga) ® and standard therapy for HFrEF.
- Subjects will be treated with medication regimens for at least 3 months
- All patients will be submitted to:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects with type-2 diabetes history >=5 years
- •HbA1C 6-10% with glucose control medications including insulin, metformin or sulfonylurea
- •Medically stable
- •Willing to participate and sign informed consent.
Exclusion Criteria
- •GFR <60 mL/min/1.73 m2
- •Unstable or rapidly progressive renal disease
- •Hypotension with SBP <100 mmHg
- •Hypersensitivity to dapagliflozin or any excipients
- •Patients with severe hepatic impairment (Child-Pugh class C)
- •Patients with active hepatitis B or C infection
- •Any of the following CV/Vascular Diseases within 3 months prior to signing the consent at enrollment, as assessed by the investigator:
- •Myocardial infarction
- •Cardiac surgery or revascularization (CABG/PTCA)
- •Unstable angina
- •HF New York Heart Association (NYHA) Class IV
- •Transient ischemic attack (TIA) or significant cerebrovascular disease
- •Unstable or previously undiagnosed arrhythmia
- •Established PAD
Arms & Interventions
Control Group
Control group will receive the standard therapy for DM & HFrEF and placebo.
Intervention: Placebo oral tablet (Drug)
Dapagliflozin
Intervention group will receive 10mg of Dapagliflozin (Forxiga) ® tablet and standard therapy for HFrEF.
Intervention: Dapagliflozin 10 MG (Drug)
Outcomes
Primary Outcomes
LV dimensions
Time Frame: 3 Months
Echocardiography
Systolic function
Time Frame: 3 Months
Echocardiography
Diastolic Function
Time Frame: 3 Months
Echocardiography
Secondary Outcomes
- Galectin -3(3 Months)
- HbA1c(3 Months)
- Myeloperoxidase (MPO)(3 Months)
- N-terminal pro b-type Natriuretic Peptide (proBNP-N)(3 Months)