E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Participants must have definite coronary heart disease: either a previous myocardial infarction or positive findings on coronary angiogram. They can have normal glucose tolerance, impaired fasting glycaemia or impaired glucose tolerance but must not be diabetic. Participants will also be overweight as defined by a waist circumference >80cm in women and >94cm in men. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051615 |
E.1.2 | Term | Atherosclerotic cardiovascular disease |
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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 |
To examine in a double blind placebo controlled randomised trial whether metformin (Glucophage 850mg bd) therapy attenuates carotid atherosclerosis in overweight, non-diabetic (including normal and impaired glucose tolerance) patients with proven cardiovascular disease who are adequately treated statin therapy. Carotid atherosclerosis will be assessed by ultrasound measurement of distal common carotid intima media thickness on 3 occasions over 1.5 years for each subject.
Primary outcome measure: comparison of change in carotid intima-media thickness (measured in mm) over 1.5 years between metformin- and placebo-treated groups. |
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E.2.2 | Secondary objectives of the trial |
We will analyse whether change in carotid atherosclerosis correlates with improvements in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HbA1C, lipid subfractions, t-PA, CRP, IL-6 and ICAM-1 using appropriate blood tests.
Furthermore, we will assess any change in two dimensional plaque area, total plaque count and total plaque volume over 1.5 years. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
o Proven coronary heart disease (prior acute coronary syndrome, prior coronary artery bypass graft or angiographically proven coronary heart disease) o Aged 35-75 years o Elevated waist circumference as per the International Diabetes Foundation criteria (94cm in men and 80cm in women) o Attending Cardiology outpatient clinics at Glasgow Royal Infirmary, the Western Infirmary, Stobhill Hospital and Royal Alexandra Hospital ; and patients identified at volunteering GP surgeries in Glasgow as approved by the Scottish Primary Care Research Network o All patients will be on statin medication.
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E.4 | Principal exclusion criteria |
o Pregnancy and/or lactation at screening o Premenopausal woman not on adequate contraception (defined as daily oral hormonal contraception or regular injectable hormonal contraception) o Known or newly diagnosed diabetes mellitus on oral glucose tolerance testing (OGTT will be performed on subjects with HbA1C 6.0-6.9% and fasting plasma glucose <7.0mmol/L at screening) o Screening results: HbA1C ≥7.0% and/or fasting plasma glucose ≥7.0mmol/L o Patients with acute coronary syndrome within the last 3 months o Stage 3 or 4 heart failure defined according to the New York Heart Association criteria o Uncontrolled angina o Contraindications to metformin (example hepatic impairment, renal impairment [eGFR <45 mL/min/1.73m2 at screening], known hypersensitivity to metformin, acute illness [dehydration, severe infection, shock, acute cardiac failure]), and suspected tissue hypoxia will be excluded.
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparison of change in distal common carotid intima media thickness, as measured in millimetres by carotid ultrasound between baseline and 1.5 years, in two groups treated with placebo or metformin 850mg bd. |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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
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The end of the trial will be the last visit of the last subject. |
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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 | 0 |
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 |