Gene Expression in Monocytes of Growth Hormone Deficient Children (GEMGH)

Growth Hormone Modulated Gene Expression in Monocytes of Healthy and Growth Hormone Deficient Children

The Growth hormone (GH) is mainly synthesized in the anterior portion of the pituitary gland and has an effect on different body areas. Secreted in the circulatory stream, growth hormone reaches the liver and here stimulates the secretion of somatomedin C better known as insulin-like growth factor 1 (IGF), which constitutes its main anabolic effector.

Growth hormone deficiency (GHD) is characterized by a delay in the statural growth in children and is correlated with a worsening of body composition, cognitive functions, lipid metabolism, bone mineralization, cardiac performance and exercise in adults. Recombinant GH (rhGH) replacement therapy can correct these alterations and therefore improve the quality of life in treated patients, and accelerate growth in children.

The optimal dosage of rhGH varies for each patient, as the response to treatment suffers from considerable inter-individual variability. To date, IGF1 is the only available biomarker whose plasma levels correlate with replacement therapy.

It is important to underline how somatomedin C does not provide information about the optimal posology of rhGH for each patient in order, therefore, to predict its adverse events and efficacy.

In addition, it has been shown that the effects mediated by the somatotropic hormone on some tissues are direct, therefore independent of the action of IGF1, whose plasma levels are not, in this case, predictive of therapeutic response.

For this reason, it is therefore necessary to identify a more specific biomarker capable of monitoring the efficacy, individual responsiveness and any adverse events in patients receiving somatotropic hormone.

The GH receptor (GHR) is expressed in several cells, including monocytes. It is therefore possible that the response of monocytes to the somatotropic hormone partially mirrors that of the chondrocyte and other cell types. Given the difficulty of obtaining osteomuscular biopsies or specific body areas in which GH mediates its biological action, the published works have identified the specific cell line in which to study the molecular effects of the hormone in monocytes, thanks to their easy accessibility and high number of GHR.

In consideration of this, the investigators propose to stimulate monocytes of healthy and GHD children in vitro with rhGH and through next generation sequencing to identify the characteristic gene expression profile. The GH responsive genes identified with this study can be used for correlation studies on the response to rhGH treatment.

Study Overview

• Status: Unknown
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Other: blood sampling

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• Italy
  • Salerno
    • Baronissi, Salerno, Italy, 84081
      • Recruiting
      • Department of Medicine and Surgery, Univeristy of Salerno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 10 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic

Description

Inclusion Criteria:

• Height lower the 3th percentile

Exclusion Criteria:

• Any endocrinopathy
• Liver, kidney or haemolymphopoietic system disorders
• Celiac disease or other chronic malabsorption conditions
• Genetic syndromes (such as Turner's S., Cystic fibrosis or Down S.)
• Drug therapies interfering with growth

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Children; healthy children, untreated, donors of monocytes	Other: blood sampling; blood sampling
GHD children; GHD children, untreated, donors of monocytes	Other: blood sampling; blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gene expression in monocytes of GHD children	analysis of RNA-seq of monocytes of healthy and GHD children	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gene expression in monocytes modulated by GH	analysis of RNA-seq of monocytes of healthy and GHD children, stimulated with GH in culture	one year

Collaborators and Investigators

• Sponsor: University of Salerno
• Investigators: Study Director: Mario Vitale, MD, University of Salerno

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2019
• Primary Completion (ANTICIPATED): April 15, 2021
• Study Completion (ANTICIPATED): April 15, 2021

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (ACTUAL): April 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: GHUSalerno

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No