Treatment of GHD Associated With CHF

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

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

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Growth Hormone Deficiency
• Intervention / Treatment: Other: Placebo; Drug: Human growth hormone

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.

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Antonio Cittadini, Full Professor of Medicine; Phone Number: +390817464375; Email: cittadin@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Administration of placebo
Active Comparator: GHD	Drug: Human growth hormone; Administration of growth hormone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 12, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Prognosis; Growth Hormone; Vascular reactivity; Placebo; Exercise capacity; LV function
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Heart Failure; Dwarfism, Pituitary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2016-004580-39

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No