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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: DAPA-LVH - Does Dapagliflozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes?

Brief 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.


Detailed Summary:

Left ventricular hypertrophy (LVH) is present in the majority of patients with type 2 diabetes, since it affects 70%. It is a strong independent predictor of cardiovascular deaths and events and is even worse than triple vessel coronary disease. The reason why LVH is so adverse is because it predates so many different cardiovascular events i.e. LVH is intrinsically arrhythmogenic and causes sudden death, it impedes left ventricular (LV) filling and leads to diastolic heart failure, it reduces coronary perfusion reserve and causes ischaemia and it causes left atrial enlargement, atrial fibrillation (AF), and cardio-embolic strokes. Controlling blood pressure (BP) and using a drug that blocks the renin-angiotensin system (RAS) are the standard approaches to the management of LVH but this approach is only partially effective since 44% of all patients with type 2 diabetes are normotensive patients with LVH. Thus "normotensive LVH" is very common. Indeed, BP only contributes 25% to the variability in LV mass seen in a population. (This is important since LVH is the same thing as a high level of LV mass). Despite a "normal" BP, normotensive LVH is just as risky as is hypertensive LVH. Nevertheless, we do know that regressing LVH irrespective of BP changes is an effective way to reduce the incidence of all major cardiovascular (CV) events including specifically sudden deaths, heart failure hospitalisations, new onset AF and strokes. The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) provides conclusive proof that in diabetes, LVH regression per se reduces future cardiovascular events (by 24%), reduces CV deaths (by 37%) and reduces total deaths (by 41%) irrespective of BP.

Since controlling BP and using an angiotensin enzyme inhibitor or angiotensin receptor blocker is only partially effective at regressing LVH, additional ways of r
Sponsor: University of Dundee

Current Primary Outcome: Change in left ventricular (LV) Mass by Cardiac MRI at 52 weeks [ Time Frame: Baseline and 52 weeks ]

To see if Dapagliflozin reduces LV mass more than placebo in participants with type 2 diabetes and LV hypertrophy


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in 24 hour blood pressure (BP) recording at 52 weeks [ Time Frame: Baseline and 52 weeks ]
    To confirm expected effect of dapagliflozin on BP
  • Change in Office blood pressure (BP) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on BP
  • Change in Body mass index at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on body mass index
  • Change in waist/hip ratio at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on waist/hip ratio
  • Change in waist circumference at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on waist circumference
  • Change in visceral fat massed with Abdominal MRI at 52 weeks [ Time Frame: Baseline and 52 weeks ]
    To assess the effect of dapagliflozin on visceral fat mass.
  • Change in HbA1c at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on HbA1c
  • Number of patients with adverse events related to treatment [ Time Frame: 4, 17, 34 and 52 weeks ]
    Urinary symptoms and hypotensive symptoms will assess the tolerability of dapagliflozin in this patient group
  • Number of participants with abnormal laboratory values [ Time Frame: 4, 17, 34 and 52 weeks ]
    Liver function tests will assess the tolerability of dapagliflozin in this patient group
  • Change in Fasting Insulin Resistance Index (FIRI) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on FIRI
  • Change in B-type Natriuretic Peptide (BNP) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on BNP
  • Change in uric acid at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on uric acid


Original Secondary Outcome: Same as current

Information By: University of Dundee

Dates:
Date Received: October 7, 2016
Date Started: December 2016
Date Completion: December 2018
Last Updated: December 20, 2016
Last Verified: November 2016