Impact of Dapagliflozin on DIAstolic Dysfunction in Type 2 Diabetic Patients

Impact of Dapagliflozin on DIAstolic Dysfunction in Type 2 Diabetic Patients: The IDDIA Study

This study aims to assess the impact of 24-week treatment of dapagliflozin in type 2 DM(diabetes mellitus) patients on diastolic dysfunction. Primary endpoint is assessing the impact of 24-week treatment of dapagliflozin in type 2 DM patients on subclinical diastolic dysfunction assessed by supine bicycle diastolic stress echocardiography. Secondary endpoint is assessing the impact of 24-week treatment of dapagliflozin in type 2 DM patients on functional capacity, he impact of 24-week treatment of dapagliflozin in type 2 DM patients at resting diastolic function. This is single-center, randomized, double-blind, placebo-controlled, parallel-arm intervention study.

This study is planned to evaluate the impact of dapagliflozin on diastolic dysfunction assessed. The dose of dapagliflozin will be 10 mg as approved.

For assessment of diastolic dysfunction, supine bicycle stress exercise echocardiography was performed, and changes in diastolic functional reserve, VO2max, exercise time, and maximal exercise capacity were assessed before and after treatment. This study will be randomized, double blind, placebo controlled, to minimize the risk of bias.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin 10mg; Drug: Placebo 10mg

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female and male aged 19~75 years
• Type 2 DM and had not reached adequate glycemic control with a stable dose of metformin, sulfonylurea, or both drugs before screening
• HbA1c 7.0% ~ 10% at screening (Patients who take metformin only: HbA1C 6.5-10%)
• Patients with ≥ grade 1 diastolic function (relaxation abnormality) at resting echocardiography
• Patients provided with the written, informed consent to participate in this study

Exclusion Criteria:

• Type 1 DM (Fasting c-peptide ≤ 0.78ng/dL(or 0.26 nM/L)), secondary diabetes, gestational diabetes
• History of diabetic ketoacidosis, hyperglycemic hyperosmolar status
• Estimated glomerular filtration rate < 60 mL/min/1.73m2
• History of chronic cystitis or recurrent urinary tract infection
• Currently on loop diuretics
• Currently on medication known to affect glucose metabolism (e.g. corticosteroids, immunosuppressants)
• Abnormal liver function (AST/ALT > x3 upper normal limit)
• On weight loss program or taking weight loss medication
• LV ejection fraction < 50% at resting echocardiography
• Uncontrolled hypertension (systolic blood pressure >200mmHg and/or diastolic blood pressure >110mmHg)
• History of acute myocardial infarction, unstable angina, coronary artery bypass graft or stroke within 6 months
• Inducible ECG abnormalities at exercise
• Cardiomyopathy, significant valvular heart disease, or a significant arrhythmia
• Patients who cannot perform supine bicycle stress echocardiography
• Pregnant or lactating women
• Subjects who the investigator deems inappropriate to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo 10mg; Matching placebo for dapagliflozin 10 mg
Experimental: Dapagliflozin; Dapagliflozin 10mg/day	Drug: Dapagliflozin 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
subclinical diastolic dysfunction assessed by supine bicycle diastolic stress echocardiography	24-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the impact of dapagliflozin on patients' functional capacity	functional capacity measured by maximum oxygen uptake (VO2max), Exercise time, Maximum exercise capacity (METs)	24-week
the impact of dapagliflozin on resting diastolic function	Diastolic function measured by LV mass index, Grade of diastolic function, Ea velocity, Left atrial volume index	24-week

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2016
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 21, 2016
• First Posted (Estimate): April 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 4-2015-1130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No