Growth Hormone Deficiency, Heart Failure, Ischemic Heart Disease
Conditions
Keywords
Heart Failure, Growth Hormone, Anabolism, Anabolic Deficiency, Hormone replacement
Brief summary
The aim of this study is to investigate the potential benefits of the correction of growth hormone (GH) deficiency with GH replacement therapy in patients with chronic heart failure due to left ventricular systolic dysfunction.
Detailed description
To date, a wide range of alterations in the GH/IGF-1 axis have been described in patients with chronic heart failure (CHF): reductions in GH levels, reductions in IGF-1 and a pattern of peripheral resistance to GH, in particular in patients with severe heart failure and cardiac cachexia. Unpublished experience of our group support the concept that a considerable amount of CHF-patients have a coexisting Growth Hormone Deficiency (GHD), defined by current guidelines(GH stimulation test). Our study hypothesis is that correction of GH deficiency in patients with chronic heart failure may exert a beneficial effect on their cardiac function and remodeling, performance status and quality-of-life. Since this was a preliminary study, no sample size calculation was performed; treatment effects from were sought in left ventricular function (as assessed by cardiac MRI), cardiopulmonary exercise performance, clinical status, vascular reactivity, biochemistry and neurohumoral markers of disease (NT-proBNP).
Interventions
DRUGSomatotropin
Subcutaneous Somatotropin (recombinant human Growth Hormone) 0.012 mg/kg every second day for 6 months
Sponsors
Federico II University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Heart Failure in ew York Heart Association functional class II to IV * Left ventricular end diastolic diameter \> 60 mm * Left ventricular ejection fraction \< 40% * Growth Hormone Deficiency (defined as a peak GH response to intravenous stimulation with GHRH + Arginine \< 9 ng/dl) * Age 18-80 years * Clinical stability, guideline-oriented maximal pharmacological therapy * Informed consent
Exclusion criteria
* Active Myocarditis * Hypertrophic Cardiomyopathy * Active endocarditis * Active malignancy * End stage renal disease * Severe liver disease (Child B-C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak VO2 | 6 months | changes in peak VO2 |
Participant flow
Recruitment details
Sixty-three patients with CHF NYHA class II-IV and GH deficiency were enrolled from December 2004 to December 2006. These patients were consecutively selected from a cohort of 158 ambulatory patients referred to our tertiary care center and, to a minor extent, patients hospitalized for CHF.
Pre-assignment details
Patients recruited during hospital stay were studied after a 3-months period of optimized medical therapy and clinical stability
Participants by arm
| Arm | Count |
|---|---|
| GH Replacement Therapy Patients will receive 6 months of substitutive somatotropin (growth hormone) therapy at a dose of 0,00415 mg/kg a day, added to their background optimized CHF therapy | 28 |
| Control Optimal CHF treatment | 28 |
| Total | 56 |
Baseline characteristics
| Characteristic | Control | GH Replacement Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 11 Participants | 13 Participants | 24.0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 15 Participants | 32.0 Participants |
| Age Continuous | 62 years STANDARD_DEVIATION 8 | 62 years STANDARD_DEVIATION 6 | 62 years STANDARD_DEVIATION 4 |
| echocardiography | 40 % of ejection fraction | 30 % of ejection fraction | 35 % of ejection fraction |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9.0 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Peak VO2
changes in peak VO2
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Replacement Therapy | Peak VO2 | 14.5 ml/kg/min | Standard Error 1 |
| Control | Peak VO2 | 12.9 ml/kg/min | Standard Error 1 |