E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low serum IGF-I and GH deficiency in patients with congestive heart failure |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 |
The objective of the study is to determine whether treatment of the low IGF-1 syndrome in patients with CHF is able to modify some functional parameters, recognized as valid surrogate end-points of CHF progression |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients of either sex affected by CHF NYHA class II-III, secondary to ischemic or idiopathic dilated cardiomyopathy
• Age range 30-80 years
• Stable medications for at least two months prior to randomization, including ACE inhibitors or AT1 antagonists and beta-blockers (unless untolerated).
• LV ejection fraction 40% or less
• Peak VO2 consumption during a CPET ≤ 16 ml/kg/min.
• LV end-diastolic dimension 55 mm or more
• Low IGF-1 levels and a satisfactory response to an IGF-1 generation test (see below)
• Positive result after GH-provocation test (PD-GHRH; cut-off GH levels defined as 18.3, 9.0, and 5.0 mg/l for normal weight, overweight and obese subjects respectively)
• Informed consent
|
|
E.4 | Principal exclusion criteria |
• Haemodynamic clinically significant primary valvular disease or significant congenital heart disease
• Acute pericarditis/myocarditis
• Inability to perform a bicycle exercise test
• Poorly controlled diabetes mellitus (HbA1c >8.5)
• Active proliferative or severe non-proliferative diabetic retinopathy
• Active and/or history of malignancy
• Evidence of progression or recurrence of an underlying intracranial tumor
• Unstable angina or recent myocardial infarction (less than 5 months)
• Severe liver disease
• Serum creatinine levels >2.5 mg/dl
• Inability to cooperate or administer the study drug
• Patients participating in any other clinical study, within 30 days prior to screening visit and/or during this particular study period
• With regard to inclusion criterion no. 7, an IGF-1 level will be considered low if below the 25th percentile of a sex and age matched population (33-35). The following cut-off values will be used: 130 ng/ml (age 30-39 y); 115 ng/ml (age 40-49 y); 105 ng/ml (age 50-59 y); 95 ng/ml (age 60-69 y); 85 ng/ml (age 70-80 y).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Increase of peak VO2 consumption by at least 2.5 ml/kg/min during maximal physical exercise test.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and after 9 months |
|
E.5.2 | Secondary end point(s) |
• LV end-systolic and end-diastolic volumes, determined by echocardiography
• LV performance indices (ejection fraction, strain, strain rate)
• LV diastolic filling
• Exercise duration
• Anaerobic threshold
• Ventilatory efficiency (VE/VCO2 slope)
• Flow mediated dilation of the brachial artery
• Quality of life
• Anxiety and depression scores
• Serum levels of NT-proBNP, inflammatory cytokines, hsCRP, testosterone and DHEA, thyroid hormones, and insulin-resistance index.
• GH pituitary generation capacity following a stimulation test
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 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
|
After 9 months of treament |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |