Type 2 Diabetes MellitusPhase 4NCT03782259
Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2
A Phase 4 study testing dapagliflozin in people with Type 2 Diabetes Mellitus and Myocardial Fibrosis, run by University of Washington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus, Myocardial Fibrosis, Myocardial Inflammation
- What is being tested?
- dapagliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Feb 2019to 16 Nov 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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)
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
Given the unmet needs for CVD risk reduction in patients with Type 2 Diabetes Mellitus (T2DM), the promising findings of more effective glucose management and reductions in overall CVD events and hospitalization for heart failure with SGLT-2 inhibition demonstrated in recent trials, and the capability of cardiac MRI (CMRI) with T1- and T2-mapping in assessments of myocardial fibrosis and inflammation, the investigators propose to conduct a staged research program using adaptive study design 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.
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.
- Being tested
- dapagliflozin, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Myocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dapagliflozinDrug
Also called Forxiga
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.
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 10mg tabs placebo matching dapagliflozin. Receives: Other: Placebo |
| Active | Active comparator | 10mg tabs of dapagliflozin Receives: Drug: dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (λ), and hematocrit using the following formulas: ECV = λ(1-hematocrit); λ = (1/T1 myocardium post-contrast-1/T1 myocardium-native)/(1/T1 blood post-contrast-1/T1 blood-native).
Measured: Approximately 12 Months
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.
Measured: Approximately 12 Months
Secondary outcomes (1)
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
Measured: Approximately 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start26 Feb 2019
- Primary completion16 Nov 2022
- Study completion16 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind and placebo controlled cardiac MRI study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Francis Kim, University of Washington
- Investigators
- Xue-Qiao Zhao, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03782259
- Sponsor's protocol ID
- STUDY00004982
- Other IDs
- ESR 17-13124
- Status last verified
- Dec 2023
- First submitted
- 24 Oct 2018
- Last updated
- 29 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cha MJ, Firoozeh N, Naumova AV, Muzi P, Ordovas KG, Wang DD, Isquith D, Maynard C, Zhao XQ, Kim F. Impact of Dapagliflozin on MRI-Derived Epicardial Adipose Tissue: Secondary Imaging Analysis of a Randomized Trial. J Magn Reson Imaging. 2026 Aug 26. doi: 10.1002/jmri.70526. Online ahead of print.
PubMed 42644318Naumova AV, Cunha GM, Kim NJ, Lu J, Isquith D, Chu B, Maynard C, Mahdavi A, Firoozeh N, Ordovas K, Zhao XQ, Kim F. Dapagliflozin-Associated Reduction in Liver Fat Is Independent of Weight Loss in Patients With Type 2 Diabetes. Obesity (Silver Spring). 2026 Mar;34(3):622-629. doi: 10.1002/oby.70134. Epub 2026 Feb 2.
PubMed 41629250Wang 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.
PubMed 38849829Wang 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.
PubMed 38585865
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03782259
- Acronym / sponsor ID
- STUDY00004982
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 26 Feb 2019 (actual)
- Primary completion
- 16 Nov 2022 (actual)
- Study completion
- 16 Nov 2022 (actual)
- First posted
- 20 Dec 2018 (actual)
- Results
- Posted 29 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Given the unmet needs for CVD risk reduction in patients with Type 2 Diabetes Mellitus (T2DM), the promising findings of more effective glucose management and reductions in overall CVD events and hospitalization for heart failure with SGLT-2 inhibition demonstrated in recent trials, and the capability of cardiac MRI (CMRI) with T1- and T2-mapping in assessments of myocardial fibrosis and inflammation, the investigators propose to conduct a staged research program using adaptive study design 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.
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.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind and placebo controlled cardiac MRI study
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo10mg tabs placebo matching dapagliflozin. |
| Active | Active comparator | Drug: dapagliflozin10mg tabs of dapagliflozin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dapagliflozinAlso: ForxigaSubjects 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. | Drug | Active |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Extracellular Volume Fraction (ECV)
Time frame: Approximately 12 Months
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 (λ), and hematocrit using the following formulas: ECV = λ(1-hematocrit); λ = (1/T1 myocardium post-contrast-1/T1 myocardium-native)/(1/T1 blood post-contrast-1/T1 blood-native).
Global Myocardial Strain
Time frame: Approximately 12 Months
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.
1 secondary outcome
T2 Relaxation Time
Time frame: Approximately 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42644318Cha MJ, Firoozeh N, Naumova AV, Muzi P, Ordovas KG, Wang DD, Isquith D, Maynard C, Zhao XQ, Kim F. Impact of Dapagliflozin on MRI-Derived Epicardial Adipose Tissue: Secondary Imaging Analysis of a Randomized Trial. J Magn Reson Imaging. 2026 Aug 26. doi: 10.1002/jmri.70526. Online ahead of print.
- Derived from this study: PubMed 41629250Naumova AV, Cunha GM, Kim NJ, Lu J, Isquith D, Chu B, Maynard C, Mahdavi A, Firoozeh N, Ordovas K, Zhao XQ, Kim F. Dapagliflozin-Associated Reduction in Liver Fat Is Independent of Weight Loss in Patients With Type 2 Diabetes. Obesity (Silver Spring). 2026 Mar;34(3):622-629. doi: 10.1002/oby.70134. Epub 2026 Feb 2.
- Derived from this study: PubMed 38849829Wang 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.
- Derived from this study: PubMed 38585865Wang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xue-Qiao Zhao, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dapagliflozin in people with Type 2 Diabetes Mellitus and Myocardial Fibrosis, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extracellular Volume Fraction (ECV) (time frame: Approximately 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03782259, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2023.