Left Ventricular Functional Changes of Uncontrolled Diabetes by Dapagliflozin Treatment Trial (ELUCIDATE)

March 19, 2023 updated by: Mackay Memorial Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan
        • Mackay Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dapagliflozin add-on group
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
Anti-diabetic medications except SGLT2 inhibitors
Other Names:
  • Metformin
  • Insulin
  • Thiazolidinediones
  • Sulfonylureas
  • Meglitinides
  • Inhibitors of dipeptidyl peptidase 4
  • α-glucosidase inhibitor
Drug: Dapagliflozin
Dapagliflozin tablet (10 mg)
Other Names:
  • Farxiga
Active Comparator: Standard of care (SOC) group
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
Anti-diabetic medications except SGLT2 inhibitors
Other Names:
  • Metformin
  • Insulin
  • Thiazolidinediones
  • Sulfonylureas
  • Meglitinides
  • Inhibitors of dipeptidyl peptidase 4
  • α-glucosidase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac global longitudinal strain (GLS)
Time Frame: Baseline to Week 24
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
Time Frame: Baseline to Week 24
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)
Time Frame: Baseline to Week 24
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
Homeostatic Model Assessment of Insulin Resistance, HOMA-IR
Time Frame: Baseline to Week 24
Change in HOMA-IR over 24 weeks
Baseline to Week 24
Plasma biomarker: Growth differentiation factor-15 (GDF-15)
Time Frame: Baseline to Week 24
Change of GDF-15 level (ng/L) over 24 weeks
Baseline to Week 24
Blood pressure
Time Frame: Baseline to Week 24
Change in SBP/DBP level (mmHg) over 24 weeks
Baseline to Week 24
HbA1c
Time Frame: Baseline to Week 24
Change in HbA1c (%) by echocardiographic measurement over 24 weeks
Baseline to Week 24
Fasting glucose
Time Frame: Baseline to Week 24
Change in fasting glucose level over 24 weeks
Baseline to Week 24
Plasma biomarker: N-terminal pro-brain natriuretic peptide (NTproBNP)
Time Frame: Baseline to Week 24
Change of NT-proBNP level (pg/mL) over 24 weeks
Baseline to Week 24
transforming growth factor beta 1 (TGF-β1)
Time Frame: Baseline to Week 24
Change of TGF-β1 level (μg/L) over 24 weeks
Baseline to Week 24
tumor necrosis factor receptor I (TNF-RI)
Time Frame: Baseline to Week 24
Change of TNF-RI level (ng/mL) over 24 weeks
Baseline to Week 24
Plasma biomarker: fatty acid binding protein 4 (FABP-4)
Time Frame: Baseline to Week 24
Change of FABP-4 level (IU/mL) over 24 weeks
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mackay Memorial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2019

Primary Completion (Actual)

May 1, 2022

Study Completion (Actual)

August 31, 2022

Study Registration Dates

First Submitted

January 26, 2019

First Submitted That Met QC Criteria

March 11, 2019

First Posted (Actual)

March 12, 2019

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 19, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18MMHIS149e

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual participant data share plan

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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