Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2
NCT ID: NCT03782259
Last Updated: 2023-12-29
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
62 participants
INTERVENTIONAL
2019-02-26
2022-11-16
Brief Summary
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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.
Detailed Description
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A total of 60 subjects with \>=18 years of age, type-2 diabetes history \>=5 years and HbA1C 7-10% will be randomized at 1:1 to Dapagliflozin 10mg or matching placebo once daily for 1 year. All subjects will be followed every 3 months for clinical and laboratory evaluations and assessments. All subjects will undergo CMRI at baseline and 1 year.
The primary myocardial strain endpoint includes global myocardial longitudinal strain (GLS). Myocardial fibrosis endpoint is change in extracellular volume fraction (ECV) as assessed by T1-mapping over 12 months. ECV combines native and contrast-enhanced T1 mapping. The change of the T1 relaxation rate (i.e., 1/T1) in blood between pre- and post-contrast imaging is converted with the blood hematocrit into a reference for plasma T1, which serves as reference for the T1 changes in tissue.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
SCREENING
QUADRUPLE
Study Groups
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Placebo
10mg tabs placebo matching dapagliflozin.
Placebo
Placebo
Active
10mg tabs of dapagliflozin
dapagliflozin
Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
Interventions
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dapagliflozin
Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
Placebo
Placebo
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
University of Washington
OTHER
Responsible Party
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Francis Kim
Professor: School of Medicine
Principal Investigators
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Xue-Qiao Zhao, MD
Role: PRINCIPAL_INVESTIGATOR
University of Washington
Locations
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University of Washington
Seattle, Washington, United States
Countries
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References
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Wang DD, Naumova AV, Isquith D, Sapp J, Huynh KA, Tucker I, Balu N, Voronyuk A, Chu B, Ordovas K, Maynard C, Tian R, Zhao XQ, Kim F. Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure. Cardiovasc Diabetol. 2024 Jun 7;23(1):197. doi: 10.1186/s12933-024-02294-z.
Wang D, Naumova A, Isquith D, Sapp J, Huynh KA, Tucker I, Balu N, Voronyuk A, Chu B, Ordovas K, Maynard C, Tian R, Zhao XQ, Kim F. Dapagliflozin Reduces Systemic Inflammation in Patients with Type 2 Diabetes Without Known Heart Failure. Res Sq [Preprint]. 2024 Mar 25:rs.3.rs-4132581. doi: 10.21203/rs.3.rs-4132581/v1.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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ESR 17-13124
Identifier Type: OTHER
Identifier Source: secondary_id
STUDY00004982
Identifier Type: -
Identifier Source: org_study_id