Left Ventricular Functional Changes of Uncontrolled Diabetes by Dapagliflozin Treatment Trial

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of the SGLT2 inhibitor dapagliflozin, as compared with standard care of diabetes, on left ventricular (LV) structural and functional change in asymptomatic type 2 diabetes mellitus (DM) patient.

Detailed Description
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The ELUCIDATE trial is a prospective, open label, randomized, active-controlled 'proof of concept'single centre study conducted in Mackay Memorial Hospital, Taipei, Taiwan. It is designed to clarify the LV remodeling by using Speckle-Tracking echocardiography to measure cardiac global longitudinal strain (GLS). A cohort of 90 type 2 DM patients with normal LV ejection fraction will be randomized to either dapagliflozin 10 mg/die or to standard of care group as an active comparator. The study consists of 5 visits (see Table 1) and will last half an year, which has been ongoing since February 2019. The primary outcomes are to detect the changes in LV mass index and cardiac GLS from baseline to 6 months after treatment initiation. The secondary outcomes include changes from baseline to 6 months in anthropometric measures, atrial-ventricular mechanics measurements, HbA1C,Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), epicardial fat and plasma biomarkers regarding cardiomyocyte remodeling and inflammation.

Official Title
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The Echocardiographic Left Ventricular Functional Changes of Uncontrolled Diabetes by the Intervention of Dapagliflozin Treatment Trial (ELUCIDATE)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Diabetes Medicines
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female affected by type 2 diabetes mellitus (T2D) for at least 6 months. Age ≥ 20 and ≤ 80 years. HbA1c levels 7.1% 9.0% . On stable (at least 3 months) antidiabetic therapy with SGLT2 inhibitors naive. On stable (at least 3 months) cardio-active therapies (e.g. anti-hypertensive drugs, diuretics or drugs for hyperlipidemia). Preserved kidney function as defined by estimated glomerular filtration rate(eGFR)> 60 mL/min/1.73m2. Preserved left ventricular function defined as EF ≥ 50% by echocardiographic screening. Exclusion Criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site). Previous enrolment or randomisation in the present study. Participation in another clinical study with an investigational product during the last 3 months. The exclusion criteria that follow are for example only; include, exclude, modify or add other criteria as appropriate. Refuse or inability to give informed consent. Patients unlikely to comply with the protocol or unable to understand the nature and possible consequences of the study. Employees of the investigator or study centre (i.e. principal investigator, sub-investigator, study coordinators, other study staff, employees, or contractors of each), with direct involvement in the proposed study or other studies under the direction of that investigator and/or study centre, as well as family members of the employees or the investigator. Pregnancy or active breast feeding. History of hospitalization for heart failure. History of stage C or D heart failure. History of myocardial infarction. History of cardiac dysrhythmia. Patients with a known hypersensitivity to Dapagliflozin or any of the excipients of the product.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin add-on group<br>T2D subjects aged 20-80 years, presenting with HbA1C 7.1-9.0%, preserved kidney function (defined as estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2), preserved LV function (defined as EF ≥ 50% by echocardiographic screening in the initial 2-week run-in period), and those treated with oral anti-diabetic drugs (except SGLT2i) and/or insulin therapy at least 3 months prior to the study were randomised to Dapagliflozin (10 mg/qd) add-on group. | Drug: Diabetes Medicines<br>* Anti-diabetic medications except SGLT2 inhibitors<br>* Other names: Insulin;Drug: Dapagliflozin<br>* Dapagliflozin tablet (10 mg)<br>* Other names: Farxiga;|
| Active Comparator: Standard of care (SOC) group<br>T2D subjects aged 20-80 years, presenting with HbA1C 7.1-9.0%, preserved kidney function (defined as estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2), preserved LV function (defined as EF ≥ 50% by echocardiographic screening in the initial 2-week run-in period), and those treated with oral anti-diabetic drugs (except SGLT2i) and/or insulin therapy at least 3 months prior to the study were randomised to SOC treatment group. | Drug: Diabetes Medicines<br>* Anti-diabetic medications except SGLT2 inhibitors<br>* Other names: Insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac global longitudinal strain (GLS) | The primary outcome is to measure the change in cardiac GLS from baseline to 6 months after dapagliflozin treatment compared to standard diabetes care. | Baseline to Week 24 | 
| Left ventricular mass index | The primary outcome is to measure the change in LVMi from baseline to 6 months | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anthropometric measures by body mass index (BMI) | Body weight in kilograms, body height in meters Body weight and height will be combined to report BMI in kg/m^2 Compare the change in anthropometric measures from baseline to 6 months | Baseline to Week 24 | 
| Blood pressure | Change in SBP/DBP level (mmHg) over 24 weeks | Baseline to Week 24 | 
| HbA1c | Change in HbA1c (%) by echocardiographic measurement over 24 weeks | Baseline to Week 24 | 
| Fasting glucose | Change in fasting glucose level over 24 weeks | Baseline to Week 24 | 
| Homeostatic Model Assessment of Insulin Resistance, HOMA-IR | Change in HOMA-IR over 24 weeks | Baseline to Week 24 | 
| Plasma biomarker: N-terminal pro-brain natriuretic peptide (NTproBNP) | Change of NT-proBNP level (pg/mL) over 24 weeks | Baseline to Week 24 | 
| transforming growth factor beta 1 (TGF-β1) | Change of TGF-β1 level (μg/L) over 24 weeks | Baseline to Week 24 | 
| Plasma biomarker: Growth differentiation factor-15 (GDF-15) | Change of GDF-15 level (ng/L) over 24 weeks | Baseline to Week 24 | 
| tumor necrosis factor receptor I (TNF-RI) | Change of TNF-RI level (ng/mL) over 24 weeks | Baseline to Week 24 | 
| Plasma biomarker: fatty acid binding protein 4 (FABP-4) | Change of FABP-4 level (IU/mL) over 24 weeks | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac remodeling, SGLT2 inhibitor, T2DM, Dapagliflozin