Impact of Dapagliflozin on DIAstolic Dysfunction in Type 2 Diabetic Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin 10mg
* Drug: Placebo 10mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin 10mg/day | Drug: Dapagliflozin 10mg<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo 10mg<br>* Matching placebo for dapagliflozin 10 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |