Low serum IGF-I and GH deficiency in patients with congestive heart failure
Conditions
Interventions
Trade Name: Saizen
Product Name: Saizen
Pharmaceutical Form: Concentrate and solvent for injection
Sponsors
University Federico II
Eligibility
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 84
Exclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: ;Primary end point(s): Increase of peak VO2 consumption by at least 2.5 ml/kg/min during maximal physical exercise test. ;Timepoint(s) of evaluation of this end point: Baseline and after 9 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 ;Timepoint(s) of evaluation of this end point: Baseline and 9 months | — |
Countries
Sweden
Outcome results
None listed