Does Dapagliflozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes?

• Status: Completed
• Trial end date: 2019-04-02
• Target enrollment: 0
• Participant gender: All

Summary

Left ventricular hypertrophy (LVH) is common in people with type 2 diabetes (70%) and is the strongest independent risk factor for cardiovascular events and all-cause mortality that there is. It is worse than triple vessel coronary disease. LVH often occurs in patients with "normal" blood pressures (BP). Apart from BP, the other three main factors causing LVH are insulin resistance, obesity and cardiac preload. Dapagliflozin reduces ALL four factors known to promote LVH i.e. Dapagliflozin reduces weight, glycaemia, preload and blood pressure and is therefore the ideal agent to reduce LVH since it uniquely attacks all four known mediators of LVH. This trial will investigate the ability of dapagliflozin to regress LVH in 64 participants with normotensive diabetes. This will be done by seeing if dapagliflozin reduces left ventricular mass as measured by cardiac magnetic resonance imaging (MRI). This trial may identify a novel way to reduce the strong independent risk factor of LVH which often persists despite optimum medical therapy in patients with diabetes. If dapagliflozin does reduce LVH, this would be a key sign of which subgroup of patients with diabetes (those with LVH) should be especially targeted with dapagliflozin.

64 participants with type 2 diabetes and LVH will be recruited through the Scottish Diabetes Research Network (SDRN), Scottish Primary Care Research Network (SPCRN) and other routes, in this single centre study. Participants will be randomised to receive either 10mg dapagliflozin or placebo daily for 12 months. Cardiac MRI will be performed at baseline and at 12 months, this will be assessed for the primary outcome of change in left ventricular mass. Secondary outcomes will examine change in 24 hour blood pressure and weight.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Collaborators: AstraZeneca; NHS Tayside
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

1. Provision of informed consent before any trial specific procedures.

2. Diagnosed with type 2 diabetes mellitus based on the current American Diabetes Association guidelines.

3. Aged >18 and <80 years

4. Body Mass Index ≥23

5. HbA1c 48-85mmol/mol (last known result within in the previous 6 months)

6. Blood pressure <145/90mmHg. Office BP at screening visit will be used however if this is above the inclusion criteria then the 24 hour or 16 hour recording at screening visit will be used to confirm that in the opinion of the PI the BP is adequately controlled.

7. Echocardiographic left ventricular (LV) hypertrophy (defined as an LV mass index of >115g/m2 for men and >95g/m2 for women indexed to body surface area or >48g/m2.7 or >44g/m2.7 when indexed to height) within the previous 6 months.

8. Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.

Exclusion Criteria:

1. 1. Any condition that in the opinion of the investigator may render the participant unable to complete the trial including non CV disease (e.g. active malignancy).

2. Participants with type 1 diabetes mellitus

3. Participants who have previously had an episode of diabetic ketoacidosis.

4. Serum Potassium or Sodium results outwith the normal range

5. Diagnosis of clinical heart failure

6. History of human immunodeficiency virus

7. LV systolic dysfunction (LVEF <45%) (last known result within in the previous 6 months)

8. eGFR <45ml/min (last known result within in the previous month)

9. Known liver function tests >3 times upper limit of normal (based on last measures and documented laboratory measurement in the previous 6 months)

10. Body weight >150Kg (unable to fit into a MRI scanner)

11. Contraindications to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)

12. Past or current treatment with any SGLT2 inhibitor

13. Allergy to any SGLT2 inhibitor or lactose or galactose intolerance

14. Current treatment with loop diuretic

15. Currently receiving long term (>30 consecutive days) treatment with an oral steroid

16. Pregnant or breast feeding participants

17. Involvement in the planning and/or conduct of the trial (applies to Astra Zeneca or representative staff and/or staff at the trial site).

18. Participation in another interventional study (other than observational trials and registries) within 30 days before visit 1.

19. Individuals considered at risk for poor protocol or medication compliance.