Treatment of GHD Associated With CHF

Study Overview
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Brief Summary
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Aim of the current study is to assess the cardiovascular effects of GH replacement therapy in patients with coexisting GHD and CHF

Detailed Description
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Multiple anabolic deficiencies are common in chronic heart failure (CHF) and identify subgroups of patients with higher mortality. Apart from CHF, GH deficiency (GHD) per se increases cardiovascular mortality in the general population and low IGF-1 levels in the general population predict the development of ischemic heart disease and CHF. GHD modifies cardiac size and function, through a reduction in both myocardial growth and cardiac performance. The investigators therefore completed 2 studies aimed at evaluating the clinical status, neurohormonal parameters, exercise capacity, vascular reactivity, and left ventricular architecture and function in patients with GHD and CHF, at baseline and after 6 months of GH replacement therapy. They subsequently extended the observation period up to 48 months. At 6-months, GH replacement therapy improved clinical status and exercise capacity, as shown by a significant reduction of the Minnesota living with heart failure questionnaire score, increased peak oxygen consumption and exercise duration, and flow mediated vasodilation of the brachial artery. No major adverse events were reported in the patients receiving GH. However, the encouraging results of these studies are limited by the lack of a double-blind, placebo-controlled design, insofar as the investigators performed a randomized controlled, single-blind study.

Official Title
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Treatment of Growth Hormone Deficiency Associated With Chronic Heart Failure: A Randomized, Double-Blind, Placebo-Controlled Study

Conditions
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Heart Failure, Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Human growth hormone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients of either sex affected by CHF NYHA class I-III, secondary to ischemic or idiopathic di-lated cardiomyopathy; age range 18-85 years; stable and optimal medical therapy for at least three months prior to randomization, including ACE inhibitors or AT1 antagonists and beta-blockers (unless untolerated); LV ejection fraction 40% or less and LV end-diastolic dimension 55 mm or more; GH deficiency diagnosed with GHRH + arginine provocative test; signed informed consent. Exclusion Criteria: inability to perform a bicycle exercise test; poorly controlled diabetes mellitus (HbA1c >8.5) and/or active proliferative or severe non-proliferative diabetic retinopathy; active and/or history of malignancy; unstable angina or recent myocardial infarction (less than six months); severe liver or kidney disease (serum creatinine levels >2.5 mg/dl

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GHD<br> | Drug: Human growth hormone<br>* Administration of growth hormone<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Administration of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of peak oxygen consumption (peak VO2) | According to previous observations, the investigators set a target increase of peak VO2 in the treated arm at 3 ml/kg/min at the end of the study | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hospitalizations |  | 1 year | 
| End-systolic LV volumes |  | 1 year | 
| NT-proBNP levels |  | 1 year | 
| Quality of life score from the Minnesota Living with Heart Failure Questionnaire | The questionnaire is comprised of 21 physical, emotional and socioeconomic questions that may adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (lower valure) to 5 (upper value) scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The final score is calculated by sum. | 1 year | 
| Evaluation of Endothelial function (flow-mediated vasodilation) |  | 1 year | 
| Muscle strength (handgrip) |  | 1 year | 
| Evaluation of the Levels of Endothelial Progenitor Cells (EPCs) |  | 1 year | 
| Evaluation of the Levels of lymphocyte G protein-coupled receptor kinase (GRK)-2 |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth Hormone, Placebo, Exercise capacity, Vascular reactivity, LV function, Prognosis