E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who has heart failure and found to be insulin resistant (pre-diabetic state). Insulin resistance can be identified using a blood test. |
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MedDRA Classification |
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 establish whether Metformin will improve exercise capacity (Peak VO2) in patient with insulin resistant Chronic Heart Failure
We will use an exercise re-breathing bicycle test called Innocor (from Denmark) to assess the cardiac output and hence work out the peak VO2. |
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E.2.2 | Secondary objectives of the trial |
If Metformin does improve exercise capacity, we would like to find out the possible mechanisms. Therefore, the following tests will be used: 1) Echo to assess pumping function 2) Flow Mediated Dilatation, Skin Laser Doppler Imaging and Endo-PaT to assess endothelial function. 3) 6 min walk test to assess exercise endurance 4) Muscle Biopsy to look at enzymes activities
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients aged 25-80 yrs with compensated CHF in NYHA functional I-III with evidence of insulin resistance [fasting insulin resistance index values of > 2.7 are said to have insulin resistance]. • Documented Left ventricular dysfunction and/or LV ejection fraction < 35%
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E.4 | Principal exclusion criteria |
(i) elderly patients (aged >80 yrs); (ii) patients with decompensated CHF (NYHA functional class IV and /or signs of decompensated CHF); (iii) renal dysfunction (serum creatinine > 160 mmol/L); (iv) Patients who are unable to exercise including patients that will be excluded for reasons of safety or potential effects on exercise performance. Therefore, patients with angina or other cardiac or pulmonary symptoms potentially limiting exercise performance will be excluded. (v) Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic blood pressure >95 mmHg at rest or >105 mmHg with exercise will also be a reason for exclusion; (vi) Patients with underlying disease likely to limit life span and/or increase risk of interventions will be excluded i.e., cancer; cardiovascular disease .i.e., uncontrolled hypertension: SBP>180 mmHg or DBP, recent stroke, any severe chronic disease (including renal and hepatic disease
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point would be peak VO2, calculated using Innocor System |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |