NCT02226510

MetfoRmin and Its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease

MetfoRmin and Its Effects on Myocardial Dimension and Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 68 (actual)
• Sponsor: University of Dundee · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Thickening of the heart muscle (left ventricle) known medically as Left Ventricular Hypertrophy (LVH) is very common in patients with heart disease. This increases risk of cerebrovascular/cardiovascular event. LVH is asymptomatic and managed by the use of medication to control blood pressure, however LVH may be seen in normotensive patients where factors such as obesity and insulin resistance are present. Insulin resistance is a condition where although the body produces insulin it is unable to utilize it effectively. Metformin, a drug used to treat diabetes, can reduce insulin resistance and cause weight loss, it may therefore improve LVH. This study will investigate the ability of metformin to reduce LVH in patients with heart disease, this may be a novel way forward in the risk reduction of cerebrovascular/cardiovascular events. Participants will be identified throughout NHS Tayside, those eligible will be randomly allocated to either metformin or a dummy medication (placebo) and will receive one year of treatment. At the beginning of the study, the thickness of the heart muscle will be measured by ultrasound scan and cardiac Magnetic Resonance Imaging (cMRI). We will also perform non-invasive tests to measure blood vessel function. These tests will be repeated after one year. At the end of the study, we will investigate the difference between placebo treatment and metformin treatment. This study is funded by the British Heart Foundation.

Detailed description

This is a single centre trial designed to investigate the benefit, if any, of 12 month metformin XL 2000mg/day treatment on left ventricular hypertrophy (LVH) in 64 nondiabetic participants with Ischaemic heart disease (IHD) and insulin resistance (IR) and/or prediabetes. Participants will be seen on seven occasions: screening, baseline/randomisation, 2 weeks post randomisation, month 1, month 4, month 8 and final month 12, during which vital signs and safety bloods will be performed. There will also be three telephone visits at: month 2, month 6 and month 10. At a screening visit an initial history will be performed following informed consent. Participants will then undergo an echocardiogram (a painless ultrasound scan of the heart) in the Department of Clinical Pharmacology, Ninewells Hospital, Dundee. Blood pressure will be recorded and blood tests to determine fasting insulin resistance index (FIRI), prediabetes and routine safety, prior to metformin administration, will be performed. Participants who meet all inclusion criteria will return for the randomisation visit within 4 weeks of screening where a Cardiac Magnetic Resonance Imaging (cMRI) scan will be performed followed by randomisation to either Metformin XL or placebo in a double blind, randomised fashion. Also, at this visit endothelial function tests will be performed to assess peripheral blood vessels in the forearm, central obesity will be quantified using waist circumference and waist to hip ratio (WHR) and study specific blood sampling performed (with participant consent). At the final visit or early withdrawal the following will be performed: vital signs, safety bloods, study specific bloods (with participant consent), echocardiography, endothelial function tests and cMRI. In the active arm, therapy will be metformin XL in an initial dose of 1000mg/day (metformin XL 500mg x2/day). Participants will continue on Metformin XL 500mg x2/day for two weeks, following safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated it will be reduced to 1000mg/day (or stopped if not tolerated). The target dose of metformin XL at 2000mg/day was chosen based on a previous study of metformin in nondiabetic heart failure patients with IR, this study demonstrated a beneficial effect of metformin on insulin resistance, weight reduction and an improvement in submaximal exercise. The study used the immediate release form of metformin (target of 1000 mg x2/day) which was associated with significant gastrointestinal side effects resulting in 13% withdrawal of study medication. For this reason we have selected metformin XR due to improved gastrointestinal tolerability.

Conditions

• Left Ventricular Hypertrophy
• Insulin Resistance
• Coronary Artery Disease
• PreDiabetes

Interventions

Type	Name	Description
DRUG	Metformin XL	In the active arm, the added therapy will be metformin XL in an initial dose of 1000mg/day . They will continue on Metformin XL 500mg x2/day for 2 weeks and after safety blood checks the metformin XL dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated the dose will be reduced to 1000mg/day.
DRUG	Placebo	Placebo capsules (with an identical appearance to the active drug) containing only microcrystalline cellulose PhEur will be administered.

Timeline

• Start date: 2015-03-01
• Primary completion: 2017-09-01
• Completion: 2017-12-01
• First posted: 2014-08-27
• Last updated: 2019-04-10

Locations

1 site across 1 country: United Kingdom