E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022489 |
E.1.2 | Term | Insulin resistance |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051615 |
E.1.2 | Term | Atherosclerotic cardiovascular disease |
E.1.2 | System Organ Class | 100000004866 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025164 |
E.1.2 | Term | LVH |
E.1.2 | System Organ Class | 100000004849 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principal research question is to find out if metformin (a drug commonly used for the treatment of type 2 diabetes)changes the thickness of the left side of the heart in patients who have heart disease and who may be at risk of developing diabetes
|
|
E.2.2 | Secondary objectives of the trial |
This study will also check if metformin improves the pumping ability of the heart, or makes it more efficient in patients with prior heart disease who may be at risk of developing diabetes in future. This will be measured by scanning the heart with an ultrasound and then an MRI scanner. We will also try to establish if metformin promotes weight loss in these patients who may benefit from a reduction in abdominal fat. The participants recruited will also be at increased risk of developing diabetes as they will have been screened for Insulin resistance. Insulin resistance is a medical term where the ability of cells in the body to use insulin is reduced resulting in a build up of sugar in the body which can lead to type 2 diabetes. We will examine if metformin improves insulin resistance in this group.
As these patients have established heart diseases and are possibly predisposed to developing diabetes we will examine if metformin improves the health of peripheral blood vessels u |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Participant is willing and able to give informed consent for participation in the study 2) Aged 18 years or over 3) Documented Ischaemic Heart Disease: either angio-graphically documented coronary artery disease or a previous history of myocardial infarction/angina. 4) Have screening echocardiography based diagnosis of LVH based on ASE criteria (males >115g/m2, females >95g/m2) 5) Fasting insulin resistance index ≥ 2.7 at screening 6) Clinic Blood pressure < 140/85 mm Hg or 24hr BP <135/85 daytime average in screening 7)Able (in the Investigators opinion) and willing to comply with all study requirements.
|
|
E.4 | Principal exclusion criteria |
1) Severe cognitive impairment precluding written informed consent 2) Type 1 or 2 Diabetes mellitus 3) Chronic Heart Failure as evidenced by an echocardiogram or a diagnosis of CHF 4) Left Ventricular Ejection Fraction <45% on echocardiography screening 5) Contraindications to cardiac MRI (pacemakers, claustrophobia, metal implants, history of penetrative eye injury or exposure to metal fragments in eye requiring medical attention) 6) Malignancy (receiving active treatment) or other life threatening diseases 7) renal disease; CKD class 3B or worse (to exclude risk of lactic acidosis) 8) Pregnancy and lactating women 9) Any other considered by a study physician to be inappropriate for inclusion 10) Participants who have participated in any other clinical trial within the previous 30 days will be excluded.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is to determine if metformin induces a change in Left Ventricular Mass Index in patients with IHD and IR when compared to placebo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline- 0 weeks Endpoint- 12 months |
|
E.5.2 | Secondary end point(s) |
• To determine if there is a change in LV Mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction with metformin in patients with IHD and IR compared with placebo. • To determine if there is a change in central and abdominal obesity with metformin in patients with IHD and IR compared with placebo. • To determine if there is a difference in endothelial function with metformin compared with placebo, measured by FMD and PWA and skin reactive hyperaemia. • To determine if there is an improvement in IR when treated with metformin compared to placebo in patients with IHD and IR. • To determine if there are changes in inflammatory and other cardiovascular blood markers, when treated with metformin compared to placebo in patients with IHD and IR. • Safety and efficacy of Metformin XR will be determined by monitoring changes from randomisation till the end of the study or so long the patient remains in the study, whichever is earlier.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline- 0 weeks Endpoint- 12 months |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |