Clinical trial NCT03871621: Left Ventricular Functional Changes of Uncontrolled Diabetes by Dapagliflozin Treatment Trial
Official title: The Echocardiographic Left Ventricular Functional Changes of Uncontrolled Diabetes by the Intervention of Dapagliflozin Treatment Trial (ELUCIDATE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Cardiac remodeling
SGLT2 inhibitor
T2DM
Dapagliflozin
Lead sponsor: Mackay Memorial Hospital
Sponsor class: OTHER
First posted: 2019-03-12
Enrollment: 76
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cardiac global longitudinal strain (GLS)
timeFrame: Baseline to Week 24
measure: Left ventricular mass index
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Anthropometric measures by body mass index (BMI)
timeFrame: Baseline to Week 24
measure: Blood pressure
timeFrame: Baseline to Week 24
measure: HbA1c
timeFrame: Baseline to Week 24
measure: Fasting glucose
timeFrame: Baseline to Week 24
measure: Homeostatic Model Assessment of Insulin Resistance, HOMA-IR
timeFrame: Baseline to Week 24
measure: Plasma biomarker: N-terminal pro-brain natriuretic peptide (NTproBNP)
timeFrame: Baseline to Week 24
measure: transforming growth factor beta 1 (TGF-β1)
timeFrame: Baseline to Week 24
measure: Plasma biomarker: Growth differentiation factor-15 (GDF-15)
timeFrame: Baseline to Week 24
measure: tumor necrosis factor receptor I (TNF-RI)
timeFrame: Baseline to Week 24
measure: Plasma biomarker: fatty acid binding protein 4 (FABP-4)
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
Study officials:
References: