The DAPA-MEMRI Trial

NCT04591639 | Recruiting

• 1 other identifier: AC20006
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes mellitus is among the top 10 causes of death worldwide with an increasing incidence. Patients with diabetes are at risk of developing heart failure which is characterised by significant changes in the heart muscle including scarring and thickening. Contraction of the heart involves movement of calcium across the heart muscle and disruption of this process is an early change seen in heart failure. Recently, a drug therapy (SGLT2 inhibitor therapy) in patients with diabetes was shown to benefit patients with heart failure but the mechanisms of benefit are unknown. Our hypothesis is that calcium handling is altered in patients with either type 2 diabetes mellitus (T2DM) or heart failure and that SGLT2 inhibitors can improve this in heart failure irrespective of the presence of T2DM. Scanning the heart using magnetic resonance imaging (MRI) enables detailed assessment of its structure and function by using a new contrast 'dye' containing manganese that has shown advantages over traditional contrast. We plan to further test this new dye as it has the potential to track and quantify improvements in heart function over time and detect changes in calcium handling in the heart muscle, making it an ideal measure to identify the mechanisms of benefit from SGLT2 inhibitor therapy. The study population will comprise patients with heart failure with and without type 2 diabetes, patients with type 2 diabetes without heart failure and healthy volunteers. Baseline comparisons will be made between the four groups before progressing to the randomised controlled trial with heart failure patients only. Patients will have a clinical assessment and blood tests, electrocardiogram, echocardiogram and MRI of the heart at each visit. If successful, this study will give us significant insights into mechanisms of action of SGLT2 inhibitors in heart failure and will enable us to tailor specific treatments in heart failure patients.

Conditions

Heart Failure; Diabetic Cardiomyopathies

Keywords

Heart failure; Sodium glucose Co-transporter 2 inhibitor therapy; Manganese enhanced cardiac magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Rate of change in myocardial T1 values with manganese enhanced cardiac MRI

  6 months

Secondary Outcomes (11)

• Left ventricular ejection fraction measured in percentage on cardiac MRI

  6 months

• Left ventricular mass measured in grams on cardiac MRI

  6 months

• Cardiac biomarkers like N-terminal pro B-type natriuretic peptide in nanogram per litre

  6 months

• Markers of diabetes control including glucose in millimoles per litre

  6 months

• Clinical measures such as heart rate in beats per minute

  6 months

Study Arms (2)

Patients with heart failure without type 2 diabetes

OTHER

60 patients with heart failure without type 2 diabetes will be recruited and will either be randomised to placebo or Dapagliflozin after their baseline cardiac MRIs. They will have 2 cardiac MRIs (gadolinium and manganese enhanced) at baseline and further manganese enhanced cardiac MRI at 1 month post randomisation + gadolinium and manganese enhanced cardiac MRI at 6 months post randomisation.

Drug: Dapagliflozin 10 milligrams [Farxiga]; Drug: Placebo

Patients with heart failure with type 2 diabetes

OTHER

60 patients with heart failure with type 2 diabetes will be recruited and will either be randomised to placebo or Dapagliflozin after their baseline cardiac MRIs. They will have 2 cardiac MRIs (gadolinium and manganese enhanced) at baseline and further manganese enhanced cardiac MRI at 1 month post randomisation + gadolinium and manganese enhanced cardiac MRI at 6 months post randomisation.

Drug: Dapagliflozin 10 milligrams [Farxiga]; Drug: Placebo

Interventions

Dapagliflozin 10 milligrams [Farxiga] DRUG

Patients with heart failure with or without type 2 diabetes will be either randomised to 10mg Dapagliflozin once daily or matched placebo.

Patients with heart failure with type 2 diabetes; Patients with heart failure without type 2 diabetes

Placebo DRUG

Patients with heart failure with or without type 2 diabetes will be either randomised to 10mg Dapagliflozin once daily or matched placebo.

Patients with heart failure with type 2 diabetes; Patients with heart failure without type 2 diabetes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with heart failure (with or without type 2 diabetes mellitus)
• Aged over 18 years
• Diagnosis of symptomatic reduced ejection fraction heart failure for at least 2 months
• Left ventricular ejection fraction ≤40%
• Elevated N-terminal pro B-type natriuretic peptide (\>125 pg/mL)
• Clinical diagnosis of type 2 diabetes mellitus for 50% of patient population - on stable therapy for at least 12 months or more.
• Patients with Type 2 Diabetes Mellitus and no heart failure
• Aged over 18 years
• Clinical diagnosis of type 2 diabetes mellitus (diagnosed by either HbA1c of 48mmol/mol (6.5%) or greater or fasting plasma glucose level of 7mmol/L or greater at the time of diagnosis)
• \- on stable therapy for at least 12 months or more.
• Normal left ventricular systolic ejection fraction
• Healthy Volunteers
• Aged over 18 years
• Normal left ventricular ejection fraction and glycaemia
• No clinically significant co-morbid conditions

You may not qualify if:

• Patients with heart failure (with or without type 2 diabetes mellitus)
• Receiving an SGLT2 inhibitor within 8 weeks of enrolment
• Previous intolerance of, or contraindication to, an SGLT2 inhibitor
• Severe renal impairment (eGFR \<30millilitre/min. 1.73m2)
• Type 1 diabetes mellitus
• Symptomatic hypotension or systolic blood pressure \<95 mmHg
• Recent (within 12 weeks) hospitalisation for heart failure, acute cardiovascular event (such as myocardial infarction or stroke) or coronary re-vascularisation.
• nd or 3rd degree atrioventricular block Atrial fibrillation or flutter with poor ventricular rate control (\>100 /min)
• Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease
• New York Heart Association grade IV heart failure
• Obstructive liver function testing abnormalities
• Concomitant digoxin, diltiazem or verapamil therapy.
• Patients with type 2 diabetes mellitus and no heart failure
• Other major clinically significant co-morbid conditions
• History of ischaemic heart disease or present history suggestive of probable clinically significant underlying ischaemic heart disease

Sponsors & Collaborators

• University of Edinburgh: lead
• AstraZeneca: collaborator
• NHS Lothian: collaborator

Study Sites (1)

University of Edinburgh

Edinburgh, Scotland, United Kingdom

RECRUITING

MeSH Terms

Conditions

Heart Failure; Diabetic Cardiomyopathies

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Central Study Contacts

Shruti Joshi, MBBS, MRCP

CONTACT

0131 650 1000; sjoshi@ed.ac.uk

David Newby, PhD, BM, DM, MRCP, DSc, FRSE

CONTACT

0131 650 1000; d.e.newby@ed.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: As above
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The observational component of the study will have 4 cohort of participants (patients with type 2 diabetes without heart failure, patients with heart failure with or without diabetes and healthy volunteers) The randomised controlled trial component of the study will have 2 groups of patients - heart failure with or without type 2 diabetes

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: October 19, 2020
• Study Start: August 19, 2020
• Primary Completion (Estimated): July 28, 2028
• Study Completion (Estimated): July 28, 2028
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)