Type 2 Diabetes Mellitus Clinical Trial
Official title:
Effects of SGLT-2 Inhibition With Dapagliflozin on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI With T1- and T2-mapping in Patients With Type-2 Diabetes
Verified date | December 2023 |
Source | University of Washington |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
There is an unmet need for Cardiovascular Disease (CVD) risk reduction in patients with Type 2 Diabetes. In recent trials there has been promising findings of more effective glucose management and reductions in overall CVD events and hospitalization for heart failure with SGLT-2 inhibition. Using the capability of cardiac MRI with T1- and T2-mapping in assessments of myocardial fibrosis and inflammation, the investigators propose to conduct a clinical trial to investigate the effects of SGLT-2 inhibition with dapagliflozin on myocardial strain, fibrosis and inflammation as assessed by cardiac MRI with T1- and T2-mapping in patients with type-2 diabetes. Over approximately 12 months subjects will have 6 clinical visits at the investigators research clinic. During this time subjects will be randomized to receive either active 10mg dapagliflozin or a matching placebo. 2 MRI scans at one of the two University of Washington research imaging centers will take place. One at randomization and the second scan will occur approximately 12 months after the first scan.
Status | Completed |
Enrollment | 62 |
Est. completion date | November 16, 2022 |
Est. primary completion date | November 16, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Men and women at least 18 years of age 2. Subjects with type-2 diabetes history >=5 years 3. HbA1C 7-10% with glucose control medications including insulin, metformin or sulfonylurea 4. Medically stable 5. Willing to participate and sign informed consent. Exclusion Criteria: 1. Contraindication to MRI 2. Currently or within last three months treatment with a SGLT2 inhibitor 3. Currently taking glucagon-like peptide (GLP)-1 receptor antagonist 4. Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 5. Unstable or rapidly progressive renal disease 6. Hypotension with systolic blood pressure (SBP) <100 mmHg 7. Hypersensitivity to dapagliflozin or any excipients 8. Patients with severe hepatic impairment (Child-Pugh class C) 9. Patients with active hepatitis B or C infection 10. Any of the following CV/Vascular Diseases within 3 months prior to signing the consent at enrollment, as assessed by the investigator: 1. Myocardial infarction 2. Cardiac surgery or revascularization (CABG/PTCA) 3. Unstable angina 4. Heart Failure - New York Heart Association (NYHA) Class IV 5. Transient ischemic attack (TIA) or significant cerebrovascular disease 6. Unstable or previously undiagnosed arrhythmia 7. Established peripheral artery disease (PAD) (18) Active bladder cancer (19) Recent episode of Diabetic ketoacidosis (DKA), frequent episodes of DKA (20) High risk of fractures, amputations and fibrosis (21) Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who have a positive pregnancy test at enrollment or randomization, OR women who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator, from the time of signing the informed consent until two weeks after the last dose of study drug, OR women who are breast-feeding. |
Country | Name | City | State |
---|---|---|---|
United States | University of Washington | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
University of Washington | AstraZeneca |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Fasting Glucose | Fasting glucose assessed at Baseline and every 3 months for approximately 12 months, Baseline and 12 months reported | Approximately 12 Months | |
Other | HbA1C | Hemoglobin A1c (HbA1c) assessed at Baseline and every 3 months for approximately 12 months, Baseline and 12 months reported | Approximately 12 Months | |
Other | hsCRP | Inflammatory marker hsCRP assessed at Baseline and every 6 months for approximately 12 months, Baseline and 12 months reported | Approximately 12 Months | |
Primary | Extracellular Volume Fraction (ECV) | Cardiac MRI using T1-mapping is capable of quantifying myocardial extracellular volume (ECV), a surrogate of fibrosis, with excellent inter- and intra-observer variability. Cardiac fibrosis was assessed by cardiac MRI T1 mapping to calculate ECV at two timepoints, baseline and at approximately 1 year. ECV combines native and contrast-enhanced T1 mapping.
Extracellular Volume (ECV) maps were generated offline using MATLAB software. ECV was calculated from native and post-contrast T1 values for blood and myocardial tissue, the partition coefficient lambda (?), and hematocrit using the following formulas: ECV = ?(1-hematocrit); ? = (1/T1 myocardium post-contrast-1/T1 myocardium-native)/(1/T1 blood post-contrast-1/T1 blood-native). |
Approximately 12 Months | |
Primary | Global Myocardial Strain | Global myocardial strain measured from cardiac MRI with T1-mapping at two timepoints. MRI at Randomization and MRI at approximately 12 Months. Myocardial strain measurements with feature tracking will be performed to measure myocardial strain from the Balanced Steady State Free Precession (bSSFP) short-axis and long-axis cine images. Long-axis cine images will be further used to compute global myocardial strain. Ancova test with adjusted for baseline global myocardial strain will be used to compare change in global myocardial strain over 12 months between 2 treatment groups.
Global myocardial strain reported as longitudinal, radial, and circumferential at baseline and 1 year. |
Approximately 12 Months | |
Secondary | T2 Relaxation Time | Change from baseline in T2 relaxation time measured from cardiac MRI with T2-mapping at two timepoints. MRI at Randomization and MRI at approximately 12 Months | Approximately 12 Months |
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