Clinical trial NCT03775993: Treatment of GHD Associated With CHF
Official title: Treatment of Growth Hormone Deficiency Associated With Chronic Heart Failure: A Randomized, Double-Blind, Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure
Growth Hormone Deficiency
Keywords: Growth Hormone
Placebo
Exercise capacity
Vascular reactivity
LV function
Prognosis
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2018-12-14
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. patients of either sex affected by CHF NYHA class I-III, secondary to ischemic or idiopathic di-lated cardiomyopathy;
2. age range 18-85 years;
3. stable and optimal medical therapy for at least three months prior to randomization, including ACE inhibitors or AT1 antagonists and beta-blockers (unless untolerated);
4. LV ejection fraction 40% or less and LV end-diastolic dimension 55 mm or more;
5. GH deficiency diagnosed with GHRH + arginine provocative test;
6. signed informed consent.

Exclusion Criteria:

1. inability to perform a bicycle exercise test;
2. poorly controlled diabetes mellitus (HbA1c \>8.5) and/or active proliferative or severe non-proliferative diabetic retinopathy;
3. active and/or history of malignancy;
4. unstable angina or recent myocardial infarction (less than six months);
5. severe liver or kidney disease (serum creatinine levels \>2.5 mg/dl

Primary outcomes:
measure: Change of peak oxygen consumption (peak VO2)
timeFrame: 1 year
Secondary outcomes:
measure: Number of Hospitalizations
timeFrame: 1 year
measure: End-systolic LV volumes
timeFrame: 1 year
measure: NT-proBNP levels
timeFrame: 1 year
measure: Quality of life score from the Minnesota Living with Heart Failure Questionnaire
timeFrame: 1 year
measure: Evaluation of Endothelial function (flow-mediated vasodilation)
timeFrame: 1 year
measure: Muscle strength (handgrip)
timeFrame: 1 year
measure: Evaluation of the Levels of Endothelial Progenitor Cells (EPCs)
timeFrame: 1 year
measure: Evaluation of the Levels of lymphocyte G protein-coupled receptor kinase (GRK)-2
timeFrame: 1 year
Other outcomes:
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