Phase 4 N=62 Randomized Quadruple-blind Screening

Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2

Type 2 Diabetes Mellitus · Myocardial Fibrosis · Myocardial Inflammation

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View on ClinicalTrials.gov: NCT03782259 ↗

Enrolled (actual)

Serious AEs

1.6%

Results posted

Dec 2023

Primary outcome: Primary: Extracellular Volume Fraction (ECV) — 28.5; 27.7; 28.7; 28.4 Percentage of total tissue volume — p=< 0 .0125

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: dapagliflozin (Drug); Placebo (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Washington
Primary completion: Nov 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Extracellular Volume Fraction (ECV)	28.5; 27.7; 28.7; 28.4; 0.24; 0.71	< 0 .0125 sig
PRIMARY Global Myocardial Strain	-11.0; -12.9; -11.3; -12.0; -0.24; 0.88	< 0 .0125 sig
SECONDARY T2 Relaxation Time	48.6; 50.5; 50.2; 50.0; 1.61; -0.51	—

Summary

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.

Eligibility Criteria

Inclusion Criteria

Men and women at least 18 years of age
Subjects with type-2 diabetes history >=5 years
HbA1C 7-10% with glucose control medications including insulin, metformin or sulfonylurea
Medically stable
Willing to participate and sign informed consent.

Exclusion Criteria

Contraindication to MRI
Currently or within last three months treatment with a SGLT2 inhibitor
Currently taking glucagon-like peptide (GLP)-1 receptor antagonist
Glomerular filtration rate (GFR) <60 mL/min/1.73 m2
Unstable or rapidly progressive renal disease
Hypotension with systolic blood pressure (SBP) <100 mmHg
Hypersensitivity to dapagliflozin or any excipients
Patients with severe hepatic impairment (Child-Pugh class C)
Patients with active hepatitis B or C infection
Any of the following CV/Vascular Diseases within 3 months prior to signing the consent at enrollment, as assessed by the investigator:
Myocardial infarction
Cardiac surgery or revascularization (CABG/PTCA)
Unstable angina
Heart Failure - New York Heart Association (NYHA) Class IV
Transient ischemic attack (TIA) or significant cerebrovascular disease
Unstable or previously undiagnosed arrhythmia
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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03782259). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.